Clinician Reviews

TOPLINE:

DMT310, a novel topical treatment applied once per week, appears to be safe and effective for moderate to severe acne.

METHODOLOGY:

• Poor patient compliance with topical acne therapies is a common clinical challenge.
• In a 12-week, randomized, controlled, phase 2b trial of 181 patients 12 years of age and older, researchers investigated the safety, tolerability, and efficacy of DMT310, a powdered mixture of Spongilla lacustris for treating moderate to severe acne. (In vitro studies have found that components of S. lacustris, a freshwater sponge, have effects that include antimicrobial activity against Cutibacterium acnes and anti-inflammatory activity in human keratinocytes).
• The study’s primary efficacy endpoint was the absolute change in inflammatory lesion count from baseline to week 12.
• Endpoint success was defined as an Investigator Global Assessment (IGA) score of 0 or 1 and at least a two-grade improvement from baseline at week 12.
•  

TAKEAWAY:

• Of the 181 patients, 91 received DMT310 (applied once a week to the face and washed off after 10-15 minutes), and 90 received placebo.
• Patients in the DMT310 arm showed a significantly greater mean reduction in the number of inflammatory lesions at week 12, compared with those in the placebo arm (–15.64 vs. –10.84, respectively; P < .001).
• Similarly, patients in the DMT310 arm showed a significantly greater mean reduction in the number of noninflammatory lesions at week 12, compared with those in the placebo arm (–18.26 vs. –12.41, respectively; P < .001).
• At week 12, endpoint success based on IGA scores also significantly favored patients in the DMT310 arm, compared with those in the placebo arm (44.40% vs. 17.78%; P < .001).

IN PRACTICE:

This study is too preliminary to have practice application. The researchers concluded that the findings “support further study of DMT310 in larger, confirmatory phase 3 trials.”

SOURCE:

Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, led the research. The study was published online June 7 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The analysis did not include an active comparator group and it enrolled a limited number of Asian patients.

DISCLOSURES:

Dr. Eichenfield disclosed that he is a consultant to Dermata, which is developing DMT310, as were three other authors of the study. One author is a company employee. The remaining authors disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

DMT310, a novel topical treatment applied once per week, appears to be safe and effective for moderate to severe acne.

METHODOLOGY:

• Poor patient compliance with topical acne therapies is a common clinical challenge.
• In a 12-week, randomized, controlled, phase 2b trial of 181 patients 12 years of age and older, researchers investigated the safety, tolerability, and efficacy of DMT310, a powdered mixture of Spongilla lacustris for treating moderate to severe acne. (In vitro studies have found that components of S. lacustris, a freshwater sponge, have effects that include antimicrobial activity against Cutibacterium acnes and anti-inflammatory activity in human keratinocytes).
• The study’s primary efficacy endpoint was the absolute change in inflammatory lesion count from baseline to week 12.
• Endpoint success was defined as an Investigator Global Assessment (IGA) score of 0 or 1 and at least a two-grade improvement from baseline at week 12.
•  

TAKEAWAY:

• Of the 181 patients, 91 received DMT310 (applied once a week to the face and washed off after 10-15 minutes), and 90 received placebo.
• Patients in the DMT310 arm showed a significantly greater mean reduction in the number of inflammatory lesions at week 12, compared with those in the placebo arm (–15.64 vs. –10.84, respectively; P < .001).
• Similarly, patients in the DMT310 arm showed a significantly greater mean reduction in the number of noninflammatory lesions at week 12, compared with those in the placebo arm (–18.26 vs. –12.41, respectively; P < .001).
• At week 12, endpoint success based on IGA scores also significantly favored patients in the DMT310 arm, compared with those in the placebo arm (44.40% vs. 17.78%; P < .001).

IN PRACTICE:

This study is too preliminary to have practice application. The researchers concluded that the findings “support further study of DMT310 in larger, confirmatory phase 3 trials.”

SOURCE:

Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, led the research. The study was published online June 7 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The analysis did not include an active comparator group and it enrolled a limited number of Asian patients.

DISCLOSURES:

Dr. Eichenfield disclosed that he is a consultant to Dermata, which is developing DMT310, as were three other authors of the study. One author is a company employee. The remaining authors disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

DMT310, a novel topical treatment applied once per week, appears to be safe and effective for moderate to severe acne.

METHODOLOGY:

• Poor patient compliance with topical acne therapies is a common clinical challenge.
• In a 12-week, randomized, controlled, phase 2b trial of 181 patients 12 years of age and older, researchers investigated the safety, tolerability, and efficacy of DMT310, a powdered mixture of Spongilla lacustris for treating moderate to severe acne. (In vitro studies have found that components of S. lacustris, a freshwater sponge, have effects that include antimicrobial activity against Cutibacterium acnes and anti-inflammatory activity in human keratinocytes).
• The study’s primary efficacy endpoint was the absolute change in inflammatory lesion count from baseline to week 12.
• Endpoint success was defined as an Investigator Global Assessment (IGA) score of 0 or 1 and at least a two-grade improvement from baseline at week 12.
•  

TAKEAWAY:

• Of the 181 patients, 91 received DMT310 (applied once a week to the face and washed off after 10-15 minutes), and 90 received placebo.
• Patients in the DMT310 arm showed a significantly greater mean reduction in the number of inflammatory lesions at week 12, compared with those in the placebo arm (–15.64 vs. –10.84, respectively; P < .001).
• Similarly, patients in the DMT310 arm showed a significantly greater mean reduction in the number of noninflammatory lesions at week 12, compared with those in the placebo arm (–18.26 vs. –12.41, respectively; P < .001).
• At week 12, endpoint success based on IGA scores also significantly favored patients in the DMT310 arm, compared with those in the placebo arm (44.40% vs. 17.78%; P < .001).

IN PRACTICE:

This study is too preliminary to have practice application. The researchers concluded that the findings “support further study of DMT310 in larger, confirmatory phase 3 trials.”

SOURCE:

Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, led the research. The study was published online June 7 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The analysis did not include an active comparator group and it enrolled a limited number of Asian patients.

DISCLOSURES:

Dr. Eichenfield disclosed that he is a consultant to Dermata, which is developing DMT310, as were three other authors of the study. One author is a company employee. The remaining authors disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved nivolumab (Opdivo) for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.

The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.

Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.

Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.

The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved nivolumab (Opdivo) for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.

The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.

Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.

Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.

The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved nivolumab (Opdivo) for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.

The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.

Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.

Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.

The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.

A version of this article appeared on Medscape.com.

WASHINGTON – A series of three higher-than-approved induction doses of the interleukin-23 inhibitor risankizumab in patients with psoriasis – and no further subsequent dosing – led to an “unprecedented” level of complete skin clearance at week 52 in a small study investigating whether high-dose IL-23 inhibition can target resident memory T cells and thereby induce long-term remission, Andrew Blauvelt, MD, MBA, reported at the annual research symposium of the National Psoriasis Foundation.

Understanding and trying to target resident memory T (Trm) cells has become a hot topic in psoriasis research, with possible importance for psoriatic arthritis as well. The cells, which normally develop within tissues in a pathogen-specific manner and persist after infections resolve, have been found in healed psoriatic skin and are believed to be responsible for recurrences of psoriasis at the same sites previously affected by the disease. Research suggests, moreover, that Trm cells are dependent on IL-23 for their survival, said Dr. Blauvelt, an investigator with the Oregon Medical Research Center, Portland.

Using an approach he has coined “knockout” therapy, 20 adult patients at the center were randomized 1:1 in double-blinded dosing to receive 300 mg or 600 mg of risankizumab (two and four times the standard initial doses, respectively) at 0, 4, and 16 weeks, and were seen every 4-6 weeks in a double-blinded follow-up period. Skin biopsies of lesional and nonlesional skin were collected at weeks 0 and 52 for RNA sequence analysis to evaluate changes in Trm cell number and effector function.

At week 28, almost all patients – 94% – achieved a Psoriasis Area and Severity Index 90 score, and 83% achieved PASI 100. At week 52, of the 18 still-enrolled patients, 69% had PASI 90 scores and 43% maintained PASI 100 scores. “We’re not curing psoriasis, but that is incredible to have 43% still clear 9 months after the last dose,” Dr. Blauvelt said.

The findings are interim results that pool the two doses of risankizumab (Skyrizi). An evaluation of maintenance of efficacy with the 300-mg versus 600-mg doses and results of the skin biopsies will be presented at the 2024 annual meeting of the American Academy of Dermatology, he said. Patients who have not had recurrences are being followed up to week 100 (unblinded).

Skin biopsy findings together with levels of clearance will “add insight as to whether high-dose IL-23 inhibition is associated with higher levels of complete clearance (i.e., PASI 100) over long periods of time, and whether remissions are associated with more profound knock-down of Trm cells,” Dr. Blauvelt wrote in an editorial on Trm cells in psoriasis published in the Journal of Psoriasis and Psoriatic Arthritis.

Risankizumab was approved by the Food and Drug Administration for moderate to severe plaque psoriasis in 2019, and for active psoriatic arthritis in 2022.
 

Impact of IL-23 inhibition

A 2021 study, Dr. Blauvelt noted in his presentation, showed that the IL-23 inhibitor guselkumab (Tremfya) reduced the number of Trm cells in healed psoriatic skin, while the IL-17A inhibitor secukinumab (Cosentyx) did not affect Trm cells.

Other researchers have concluded that local IL-23 is required for the proliferation and retention of Trm cells in the skin, he said, noting also that, as a class, IL-23 blockers “are associated with the longest disease-free intervals” in patients with psoriasis.

Research showing loss of Trm cells in biopsies of cleared skin is “incredibly important,” as is data showing that IL-23 may be “a critical survival factor” for Trm cells, said Christopher Ritchlin, MD, MPH, a rheumatologist and director of the clinical immunology research unit at the University of Rochester (N.Y.) Medical Center, who attended the NPF meeting and was asked to comment on the growing interest in Trm cells. He did not hear Dr. Blauvelt’s presentation but has followed Trm research in psoriasis.

Measuring Trm cells in synovial tissue of patients with psoriatic disease is, in fact, on the agenda of a new research team coled by Dr. Ritchlin that is part of the Autoimmune and Immune-Mediated Diseases Program of the Accelerating Medicine Partnership – a public-private partnership that aims to collect and analyze troves of biological data in order to illuminate the cellular and molecular interactions leading to autoimmune diseases.

“Resident memory T cells have been thought to be cells that are constrained to being resident in the tissue, and while that’s largely true, there’s more recent data showing that they actually can dedifferentiate and go back to the lymph node and then go back to the joint again,” Dr. Ritchlin noted in an interview. “So it’s a more complicated story,” but nonetheless targeting the cells is a concept worth exploring therapeutically.
 

Moving toward a cure?

The high induction doses of risankizumab in Dr. Blauvelt’s phase 2 “knockout” study were well tolerated through week 40, with safety profiles similar overall to those reported in previous studies of risankizumab and “no new safety signals,” Dr. Blauvelt said at the meeting.

(At baseline, patients had a mean disease duration of 21 years, a mean affected BSA of 21, and a mean PASI of 18.5. Seven had prior treatment with biologic medications, though not in the prior 4 months and not with risankizumab.)

In lieu of a cure, which is still possible in the next 10 years, he said, patients are eager for longer-term remission and the ability to break away from established regular dosing. After publication of a phase 1 study of risankizumab, in which a notable number of patients experienced complete skin clearance up to 1 year following a single high dose, “we started getting numerous calls in our [clinical trials] office from patients who said ‘I want to be on that drug that you give once a year,’ ” Dr. Blauvelt said. (The high dosing was not investigated any further in phase 2 and 3 research, he added.)

While the “knockout” study adopts a “hit hard” approach, it is also possible that a strategy to hit both hard and early after disease onset may induce long-term remission and/or cure of the disease. “I’m talking about using the best things first. There are hints that if we treat early, maybe we can keep [psoriasis] from becoming a chronic disease, keep it from ‘setting up shop’ if you will,” he said, noting that the “hit hard, hit early” concept is not unique to dermatology.

During a discussion period, Dr. Blauvelt said that in a future iteration of the “knockout” study, he would like to evaluate risankizumab in patients with disease duration under 12 months. It may also be valuable to look not only at Trm cells, but more broadly at other elements of the tissue architecture before and after treatment.

Among other strategies for achieving long-term remission and/or cure is the expansion of regulatory T cells, which work to “control inappropriate immune responses” and calm inflammation. Defects in the number and function of regulatory T cells are associated with psoriasis and other autoimmune diseases, and it appears in early research from other investigators that low-dose IL-2 can induce the expansion of regulatory T cells and improve psoriasis. “Keep tuned,” Dr. Blauvelt said.

Dr. Blauvelt disclosed ties with numerous pharmaceutical companies. Dr. Ritchlin had no disclosures.

WASHINGTON – A series of three higher-than-approved induction doses of the interleukin-23 inhibitor risankizumab in patients with psoriasis – and no further subsequent dosing – led to an “unprecedented” level of complete skin clearance at week 52 in a small study investigating whether high-dose IL-23 inhibition can target resident memory T cells and thereby induce long-term remission, Andrew Blauvelt, MD, MBA, reported at the annual research symposium of the National Psoriasis Foundation.

Understanding and trying to target resident memory T (Trm) cells has become a hot topic in psoriasis research, with possible importance for psoriatic arthritis as well. The cells, which normally develop within tissues in a pathogen-specific manner and persist after infections resolve, have been found in healed psoriatic skin and are believed to be responsible for recurrences of psoriasis at the same sites previously affected by the disease. Research suggests, moreover, that Trm cells are dependent on IL-23 for their survival, said Dr. Blauvelt, an investigator with the Oregon Medical Research Center, Portland.

Using an approach he has coined “knockout” therapy, 20 adult patients at the center were randomized 1:1 in double-blinded dosing to receive 300 mg or 600 mg of risankizumab (two and four times the standard initial doses, respectively) at 0, 4, and 16 weeks, and were seen every 4-6 weeks in a double-blinded follow-up period. Skin biopsies of lesional and nonlesional skin were collected at weeks 0 and 52 for RNA sequence analysis to evaluate changes in Trm cell number and effector function.

At week 28, almost all patients – 94% – achieved a Psoriasis Area and Severity Index 90 score, and 83% achieved PASI 100. At week 52, of the 18 still-enrolled patients, 69% had PASI 90 scores and 43% maintained PASI 100 scores. “We’re not curing psoriasis, but that is incredible to have 43% still clear 9 months after the last dose,” Dr. Blauvelt said.

The findings are interim results that pool the two doses of risankizumab (Skyrizi). An evaluation of maintenance of efficacy with the 300-mg versus 600-mg doses and results of the skin biopsies will be presented at the 2024 annual meeting of the American Academy of Dermatology, he said. Patients who have not had recurrences are being followed up to week 100 (unblinded).

Skin biopsy findings together with levels of clearance will “add insight as to whether high-dose IL-23 inhibition is associated with higher levels of complete clearance (i.e., PASI 100) over long periods of time, and whether remissions are associated with more profound knock-down of Trm cells,” Dr. Blauvelt wrote in an editorial on Trm cells in psoriasis published in the Journal of Psoriasis and Psoriatic Arthritis.

Risankizumab was approved by the Food and Drug Administration for moderate to severe plaque psoriasis in 2019, and for active psoriatic arthritis in 2022.
 

Impact of IL-23 inhibition

A 2021 study, Dr. Blauvelt noted in his presentation, showed that the IL-23 inhibitor guselkumab (Tremfya) reduced the number of Trm cells in healed psoriatic skin, while the IL-17A inhibitor secukinumab (Cosentyx) did not affect Trm cells.

Other researchers have concluded that local IL-23 is required for the proliferation and retention of Trm cells in the skin, he said, noting also that, as a class, IL-23 blockers “are associated with the longest disease-free intervals” in patients with psoriasis.

Research showing loss of Trm cells in biopsies of cleared skin is “incredibly important,” as is data showing that IL-23 may be “a critical survival factor” for Trm cells, said Christopher Ritchlin, MD, MPH, a rheumatologist and director of the clinical immunology research unit at the University of Rochester (N.Y.) Medical Center, who attended the NPF meeting and was asked to comment on the growing interest in Trm cells. He did not hear Dr. Blauvelt’s presentation but has followed Trm research in psoriasis.

Measuring Trm cells in synovial tissue of patients with psoriatic disease is, in fact, on the agenda of a new research team coled by Dr. Ritchlin that is part of the Autoimmune and Immune-Mediated Diseases Program of the Accelerating Medicine Partnership – a public-private partnership that aims to collect and analyze troves of biological data in order to illuminate the cellular and molecular interactions leading to autoimmune diseases.

“Resident memory T cells have been thought to be cells that are constrained to being resident in the tissue, and while that’s largely true, there’s more recent data showing that they actually can dedifferentiate and go back to the lymph node and then go back to the joint again,” Dr. Ritchlin noted in an interview. “So it’s a more complicated story,” but nonetheless targeting the cells is a concept worth exploring therapeutically.
 

Moving toward a cure?

The high induction doses of risankizumab in Dr. Blauvelt’s phase 2 “knockout” study were well tolerated through week 40, with safety profiles similar overall to those reported in previous studies of risankizumab and “no new safety signals,” Dr. Blauvelt said at the meeting.

(At baseline, patients had a mean disease duration of 21 years, a mean affected BSA of 21, and a mean PASI of 18.5. Seven had prior treatment with biologic medications, though not in the prior 4 months and not with risankizumab.)

In lieu of a cure, which is still possible in the next 10 years, he said, patients are eager for longer-term remission and the ability to break away from established regular dosing. After publication of a phase 1 study of risankizumab, in which a notable number of patients experienced complete skin clearance up to 1 year following a single high dose, “we started getting numerous calls in our [clinical trials] office from patients who said ‘I want to be on that drug that you give once a year,’ ” Dr. Blauvelt said. (The high dosing was not investigated any further in phase 2 and 3 research, he added.)

While the “knockout” study adopts a “hit hard” approach, it is also possible that a strategy to hit both hard and early after disease onset may induce long-term remission and/or cure of the disease. “I’m talking about using the best things first. There are hints that if we treat early, maybe we can keep [psoriasis] from becoming a chronic disease, keep it from ‘setting up shop’ if you will,” he said, noting that the “hit hard, hit early” concept is not unique to dermatology.

During a discussion period, Dr. Blauvelt said that in a future iteration of the “knockout” study, he would like to evaluate risankizumab in patients with disease duration under 12 months. It may also be valuable to look not only at Trm cells, but more broadly at other elements of the tissue architecture before and after treatment.

Among other strategies for achieving long-term remission and/or cure is the expansion of regulatory T cells, which work to “control inappropriate immune responses” and calm inflammation. Defects in the number and function of regulatory T cells are associated with psoriasis and other autoimmune diseases, and it appears in early research from other investigators that low-dose IL-2 can induce the expansion of regulatory T cells and improve psoriasis. “Keep tuned,” Dr. Blauvelt said.

Dr. Blauvelt disclosed ties with numerous pharmaceutical companies. Dr. Ritchlin had no disclosures.

WASHINGTON – A series of three higher-than-approved induction doses of the interleukin-23 inhibitor risankizumab in patients with psoriasis – and no further subsequent dosing – led to an “unprecedented” level of complete skin clearance at week 52 in a small study investigating whether high-dose IL-23 inhibition can target resident memory T cells and thereby induce long-term remission, Andrew Blauvelt, MD, MBA, reported at the annual research symposium of the National Psoriasis Foundation.

Understanding and trying to target resident memory T (Trm) cells has become a hot topic in psoriasis research, with possible importance for psoriatic arthritis as well. The cells, which normally develop within tissues in a pathogen-specific manner and persist after infections resolve, have been found in healed psoriatic skin and are believed to be responsible for recurrences of psoriasis at the same sites previously affected by the disease. Research suggests, moreover, that Trm cells are dependent on IL-23 for their survival, said Dr. Blauvelt, an investigator with the Oregon Medical Research Center, Portland.

Using an approach he has coined “knockout” therapy, 20 adult patients at the center were randomized 1:1 in double-blinded dosing to receive 300 mg or 600 mg of risankizumab (two and four times the standard initial doses, respectively) at 0, 4, and 16 weeks, and were seen every 4-6 weeks in a double-blinded follow-up period. Skin biopsies of lesional and nonlesional skin were collected at weeks 0 and 52 for RNA sequence analysis to evaluate changes in Trm cell number and effector function.

At week 28, almost all patients – 94% – achieved a Psoriasis Area and Severity Index 90 score, and 83% achieved PASI 100. At week 52, of the 18 still-enrolled patients, 69% had PASI 90 scores and 43% maintained PASI 100 scores. “We’re not curing psoriasis, but that is incredible to have 43% still clear 9 months after the last dose,” Dr. Blauvelt said.

The findings are interim results that pool the two doses of risankizumab (Skyrizi). An evaluation of maintenance of efficacy with the 300-mg versus 600-mg doses and results of the skin biopsies will be presented at the 2024 annual meeting of the American Academy of Dermatology, he said. Patients who have not had recurrences are being followed up to week 100 (unblinded).

Skin biopsy findings together with levels of clearance will “add insight as to whether high-dose IL-23 inhibition is associated with higher levels of complete clearance (i.e., PASI 100) over long periods of time, and whether remissions are associated with more profound knock-down of Trm cells,” Dr. Blauvelt wrote in an editorial on Trm cells in psoriasis published in the Journal of Psoriasis and Psoriatic Arthritis.

Risankizumab was approved by the Food and Drug Administration for moderate to severe plaque psoriasis in 2019, and for active psoriatic arthritis in 2022.
 

Impact of IL-23 inhibition

A 2021 study, Dr. Blauvelt noted in his presentation, showed that the IL-23 inhibitor guselkumab (Tremfya) reduced the number of Trm cells in healed psoriatic skin, while the IL-17A inhibitor secukinumab (Cosentyx) did not affect Trm cells.

Other researchers have concluded that local IL-23 is required for the proliferation and retention of Trm cells in the skin, he said, noting also that, as a class, IL-23 blockers “are associated with the longest disease-free intervals” in patients with psoriasis.

Research showing loss of Trm cells in biopsies of cleared skin is “incredibly important,” as is data showing that IL-23 may be “a critical survival factor” for Trm cells, said Christopher Ritchlin, MD, MPH, a rheumatologist and director of the clinical immunology research unit at the University of Rochester (N.Y.) Medical Center, who attended the NPF meeting and was asked to comment on the growing interest in Trm cells. He did not hear Dr. Blauvelt’s presentation but has followed Trm research in psoriasis.

Measuring Trm cells in synovial tissue of patients with psoriatic disease is, in fact, on the agenda of a new research team coled by Dr. Ritchlin that is part of the Autoimmune and Immune-Mediated Diseases Program of the Accelerating Medicine Partnership – a public-private partnership that aims to collect and analyze troves of biological data in order to illuminate the cellular and molecular interactions leading to autoimmune diseases.

“Resident memory T cells have been thought to be cells that are constrained to being resident in the tissue, and while that’s largely true, there’s more recent data showing that they actually can dedifferentiate and go back to the lymph node and then go back to the joint again,” Dr. Ritchlin noted in an interview. “So it’s a more complicated story,” but nonetheless targeting the cells is a concept worth exploring therapeutically.
 

Moving toward a cure?

The high induction doses of risankizumab in Dr. Blauvelt’s phase 2 “knockout” study were well tolerated through week 40, with safety profiles similar overall to those reported in previous studies of risankizumab and “no new safety signals,” Dr. Blauvelt said at the meeting.

(At baseline, patients had a mean disease duration of 21 years, a mean affected BSA of 21, and a mean PASI of 18.5. Seven had prior treatment with biologic medications, though not in the prior 4 months and not with risankizumab.)

In lieu of a cure, which is still possible in the next 10 years, he said, patients are eager for longer-term remission and the ability to break away from established regular dosing. After publication of a phase 1 study of risankizumab, in which a notable number of patients experienced complete skin clearance up to 1 year following a single high dose, “we started getting numerous calls in our [clinical trials] office from patients who said ‘I want to be on that drug that you give once a year,’ ” Dr. Blauvelt said. (The high dosing was not investigated any further in phase 2 and 3 research, he added.)

While the “knockout” study adopts a “hit hard” approach, it is also possible that a strategy to hit both hard and early after disease onset may induce long-term remission and/or cure of the disease. “I’m talking about using the best things first. There are hints that if we treat early, maybe we can keep [psoriasis] from becoming a chronic disease, keep it from ‘setting up shop’ if you will,” he said, noting that the “hit hard, hit early” concept is not unique to dermatology.

During a discussion period, Dr. Blauvelt said that in a future iteration of the “knockout” study, he would like to evaluate risankizumab in patients with disease duration under 12 months. It may also be valuable to look not only at Trm cells, but more broadly at other elements of the tissue architecture before and after treatment.

Among other strategies for achieving long-term remission and/or cure is the expansion of regulatory T cells, which work to “control inappropriate immune responses” and calm inflammation. Defects in the number and function of regulatory T cells are associated with psoriasis and other autoimmune diseases, and it appears in early research from other investigators that low-dose IL-2 can induce the expansion of regulatory T cells and improve psoriasis. “Keep tuned,” Dr. Blauvelt said.

Dr. Blauvelt disclosed ties with numerous pharmaceutical companies. Dr. Ritchlin had no disclosures.

TOPLINE:

The prevalence of reported diagnosed arthritis in the United States is highest overall in older adults with comorbid chronic conditions.

METHODOLOGY:

• Researchers reviewed data from the National Health Interview Survey (NHIS) from 2019 to 2021 to update the prevalence of self-reported arthritis in the United States.
• The sample sizes for the 2019, 2020, and 2021 NHIS were 31,997, 21,153, and 29,482, with survey response rates of 59.1%, 48.9%, and 50.9%, respectively.
• The unadjusted and age-standardized prevalence estimates were calculated for adults aged 18 years and older and based on self-reported health and demographic data.

TAKEAWAY:

• Overall, arthritis was diagnosed in 53.2 million adults aged 18 years and older in the United States; of these, 88.3% were aged 45 years and older and 48.3% were 65 years and older.
• Age-standardized prevalence of arthritis was higher in women vs men and among veterans vs nonveterans (20.9% vs 16.3% and 24.2% vs 18.5%, respectively).
• When categorized by race, age-standardized prevalence of arthritis was higher among non-Hispanic White individuals, compared with Hispanic or Latino individuals or non-Hispanic Asian individuals (20.1%, 14.7%, and 10.3%, respectively).
• The prevalence of arthritis also was higher among individuals with self-reported diagnosis of chronic conditions including dementia, chronic obstructive pulmonary disease, stroke, heart disease, diabetes, and cancer than in those without these conditions; approximately half of adults aged 65 years and older with arthritis reported at least one of these conditions.

IN PRACTICE:

“These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other community-based, arthritis-appropriate, evidence-based interventions,” the authors write.

SOURCE:

The study was led by Elizabeth A. Fallon, PhD, of the Centers for Disease Control and Prevention, Atlanta, Georgia. The data were published online in the CDC’s Morbidity and Mortality Weekly Report.  

LIMITATIONS:

The cross-sectional design prevented conclusions of causality between individual characteristics and arthritis diagnosis; other limitations included the reliance on self-reports, possible response bias, and the inability to calculate prevalence of arthritis subtypes. 

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

TOPLINE:

The prevalence of reported diagnosed arthritis in the United States is highest overall in older adults with comorbid chronic conditions.

METHODOLOGY:

• Researchers reviewed data from the National Health Interview Survey (NHIS) from 2019 to 2021 to update the prevalence of self-reported arthritis in the United States.
• The sample sizes for the 2019, 2020, and 2021 NHIS were 31,997, 21,153, and 29,482, with survey response rates of 59.1%, 48.9%, and 50.9%, respectively.
• The unadjusted and age-standardized prevalence estimates were calculated for adults aged 18 years and older and based on self-reported health and demographic data.

TAKEAWAY:

• Overall, arthritis was diagnosed in 53.2 million adults aged 18 years and older in the United States; of these, 88.3% were aged 45 years and older and 48.3% were 65 years and older.
• Age-standardized prevalence of arthritis was higher in women vs men and among veterans vs nonveterans (20.9% vs 16.3% and 24.2% vs 18.5%, respectively).
• When categorized by race, age-standardized prevalence of arthritis was higher among non-Hispanic White individuals, compared with Hispanic or Latino individuals or non-Hispanic Asian individuals (20.1%, 14.7%, and 10.3%, respectively).
• The prevalence of arthritis also was higher among individuals with self-reported diagnosis of chronic conditions including dementia, chronic obstructive pulmonary disease, stroke, heart disease, diabetes, and cancer than in those without these conditions; approximately half of adults aged 65 years and older with arthritis reported at least one of these conditions.

IN PRACTICE:

“These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other community-based, arthritis-appropriate, evidence-based interventions,” the authors write.

SOURCE:

The study was led by Elizabeth A. Fallon, PhD, of the Centers for Disease Control and Prevention, Atlanta, Georgia. The data were published online in the CDC’s Morbidity and Mortality Weekly Report.  

LIMITATIONS:

The cross-sectional design prevented conclusions of causality between individual characteristics and arthritis diagnosis; other limitations included the reliance on self-reports, possible response bias, and the inability to calculate prevalence of arthritis subtypes. 

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

TOPLINE:

The prevalence of reported diagnosed arthritis in the United States is highest overall in older adults with comorbid chronic conditions.

METHODOLOGY:

• Researchers reviewed data from the National Health Interview Survey (NHIS) from 2019 to 2021 to update the prevalence of self-reported arthritis in the United States.
• The sample sizes for the 2019, 2020, and 2021 NHIS were 31,997, 21,153, and 29,482, with survey response rates of 59.1%, 48.9%, and 50.9%, respectively.
• The unadjusted and age-standardized prevalence estimates were calculated for adults aged 18 years and older and based on self-reported health and demographic data.

TAKEAWAY:

• Overall, arthritis was diagnosed in 53.2 million adults aged 18 years and older in the United States; of these, 88.3% were aged 45 years and older and 48.3% were 65 years and older.
• Age-standardized prevalence of arthritis was higher in women vs men and among veterans vs nonveterans (20.9% vs 16.3% and 24.2% vs 18.5%, respectively).
• When categorized by race, age-standardized prevalence of arthritis was higher among non-Hispanic White individuals, compared with Hispanic or Latino individuals or non-Hispanic Asian individuals (20.1%, 14.7%, and 10.3%, respectively).
• The prevalence of arthritis also was higher among individuals with self-reported diagnosis of chronic conditions including dementia, chronic obstructive pulmonary disease, stroke, heart disease, diabetes, and cancer than in those without these conditions; approximately half of adults aged 65 years and older with arthritis reported at least one of these conditions.

IN PRACTICE:

“These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other community-based, arthritis-appropriate, evidence-based interventions,” the authors write.

SOURCE:

The study was led by Elizabeth A. Fallon, PhD, of the Centers for Disease Control and Prevention, Atlanta, Georgia. The data were published online in the CDC’s Morbidity and Mortality Weekly Report.  

LIMITATIONS:

The cross-sectional design prevented conclusions of causality between individual characteristics and arthritis diagnosis; other limitations included the reliance on self-reports, possible response bias, and the inability to calculate prevalence of arthritis subtypes. 

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

HAMBURG, GERMANY – Testosterone replacement therapy was associated with significant reductions in hemoglobin A1c at 1 and 2 years among men with type 2 diabetes, a multinational audit shows.

“If you have a patient with type 2 diabetes, sexual dysfunction, or fatigue, please consider checking their testosterone level. And if they fulfill criteria for testosterone deficiency and have had their [prostate-specific antigen] checked, consider a trial of treatment and follow them,” study lead author T. Hugh Jones, MD, consultant physician and endocrinologist at Barnsley (England) Hospital NHS Foundation Trust advised, speaking with this news organization.

Dr. Jones also urges clinicians worldwide to enter their patients’ data into the ABCD Testosterone Audit, which aims to identify long-term outcomes and predictors of response to testosterone replacement therapy.

Dr. Jones, who is also professor of andrology at the University of Sheffield, presented the preliminary data analysis at the annual meeting of the European Association for the Study of Diabetes.

Thus far, a total of 428 men with type 2 diabetes and hypogonadism are entered into the audit, from 34 centers in eight countries: the United Kingdom, Germany, Canada, Brazil, South Africa, New Zealand, Malaysia, and Vietnam. Among 121 of the men at 12 months, there was a drop in A1c from a baseline level of 71.27 mmol/mol (8.7%) to 61.26 mmol/mol (7.8%). Among 104 men at 24 months, the drop was from 71.4 mmol/mol (8.7%) to 55.97 mmol/mol (7.3%). Both decreases were significant (P < .001).

Prior data from Dr. Jones’ group showed that about 40% of men with type 2 diabetes have symptomatic testosterone deficiency. Testosterone deficiency is also associated with adverse effects on cardiovascular risk factors, bone health, muscle strength, sexual function, and psychological well-being, yet it is often overlooked, Dr. Jones noted.

“It’s not typically measured in routine clinical practice. ... Deficiency is very common, but a lot of practitioners don’t treat it and don’t ask about it. But in fact, treatment has very significant benefits for patients. ... We know from sildenafil (Viagra) studies that 60%of people who didn’t respond were testosterone deficient. After being given testosterone, they converted to Viagra responders,” he noted.

Regarding safety concerns, the recent findings from the TRAVERSE study, in which about 70% of participants had type 2 diabetes, demonstrated no increased cardiovascular risk. There was also no association with prostate cancer, although it’s important to monitor prostate-specific antigen in patients for the first year on testosterone replacement, Dr. Jones said.

Asked to comment, endocrinologist Bradley D. Anawalt, MD, chief of medicine at the University of Washington Medical Center, Seattle, told this news organization, “This ‘worldwide survey’ confirms many studies from around the world over the past 20 years. ... [T]he association is due to ‘reverse causation,’ in that diabetes type 2 and obesity lower testosterone concentrations. Weight loss of 5%-10% may raise testosterone concentrations in men with high body mass indices, large waist circumferences, and low blood testosterone concentrations.”

At the same time, Dr. Anawalt pointed to data suggesting that “[t]reatment of androgen deficiency may facilitate lifestyle measures in men with high [body mass indexes] and high risk of type 2 diabetes to prevent, or more likely delay, the development of type 2 diabetes.”

However, both Dr. Jones and Dr. Anawalt emphasized that testosterone therapy would not be expected to affect blood glucose levels or any other cardiometabolic parameters in men who are not testosterone deficient, regardless of diabetes status.

“It’s important when you give testosterone to replace it to the normal level. Adequate treatment gives the greatest benefit,”Dr. Jones said.

As more centers contribute data to the ABCD audit, Jones anticipates collecting clinical practice data on a variety of clinical parameters, including complications, total insulin dose, kidney function, and eventually cardiovascular outcomes.

In the meantime, he said, giving testosterone replacement to men with deficiency can be very rewarding for many reasons. “People feel better. Individual patients come back and say ‘thank you doctor, you’ve given me my life back.’ It’s not often you get that. And the compliance is excellent.”

Dr. Jones is a speaker for, advisory board member for, and/or travel grant recipient of Besins Healthcare, Grantss, Grunenthal, and Simple Pharma. Dr. Anawalt has no disclosures.

A version of this article first appeared on Medscape.com.

HAMBURG, GERMANY – Testosterone replacement therapy was associated with significant reductions in hemoglobin A1c at 1 and 2 years among men with type 2 diabetes, a multinational audit shows.

“If you have a patient with type 2 diabetes, sexual dysfunction, or fatigue, please consider checking their testosterone level. And if they fulfill criteria for testosterone deficiency and have had their [prostate-specific antigen] checked, consider a trial of treatment and follow them,” study lead author T. Hugh Jones, MD, consultant physician and endocrinologist at Barnsley (England) Hospital NHS Foundation Trust advised, speaking with this news organization.

Dr. Jones also urges clinicians worldwide to enter their patients’ data into the ABCD Testosterone Audit, which aims to identify long-term outcomes and predictors of response to testosterone replacement therapy.

Dr. Jones, who is also professor of andrology at the University of Sheffield, presented the preliminary data analysis at the annual meeting of the European Association for the Study of Diabetes.

Thus far, a total of 428 men with type 2 diabetes and hypogonadism are entered into the audit, from 34 centers in eight countries: the United Kingdom, Germany, Canada, Brazil, South Africa, New Zealand, Malaysia, and Vietnam. Among 121 of the men at 12 months, there was a drop in A1c from a baseline level of 71.27 mmol/mol (8.7%) to 61.26 mmol/mol (7.8%). Among 104 men at 24 months, the drop was from 71.4 mmol/mol (8.7%) to 55.97 mmol/mol (7.3%). Both decreases were significant (P < .001).

Prior data from Dr. Jones’ group showed that about 40% of men with type 2 diabetes have symptomatic testosterone deficiency. Testosterone deficiency is also associated with adverse effects on cardiovascular risk factors, bone health, muscle strength, sexual function, and psychological well-being, yet it is often overlooked, Dr. Jones noted.

“It’s not typically measured in routine clinical practice. ... Deficiency is very common, but a lot of practitioners don’t treat it and don’t ask about it. But in fact, treatment has very significant benefits for patients. ... We know from sildenafil (Viagra) studies that 60%of people who didn’t respond were testosterone deficient. After being given testosterone, they converted to Viagra responders,” he noted.

Regarding safety concerns, the recent findings from the TRAVERSE study, in which about 70% of participants had type 2 diabetes, demonstrated no increased cardiovascular risk. There was also no association with prostate cancer, although it’s important to monitor prostate-specific antigen in patients for the first year on testosterone replacement, Dr. Jones said.

Asked to comment, endocrinologist Bradley D. Anawalt, MD, chief of medicine at the University of Washington Medical Center, Seattle, told this news organization, “This ‘worldwide survey’ confirms many studies from around the world over the past 20 years. ... [T]he association is due to ‘reverse causation,’ in that diabetes type 2 and obesity lower testosterone concentrations. Weight loss of 5%-10% may raise testosterone concentrations in men with high body mass indices, large waist circumferences, and low blood testosterone concentrations.”

At the same time, Dr. Anawalt pointed to data suggesting that “[t]reatment of androgen deficiency may facilitate lifestyle measures in men with high [body mass indexes] and high risk of type 2 diabetes to prevent, or more likely delay, the development of type 2 diabetes.”

However, both Dr. Jones and Dr. Anawalt emphasized that testosterone therapy would not be expected to affect blood glucose levels or any other cardiometabolic parameters in men who are not testosterone deficient, regardless of diabetes status.

“It’s important when you give testosterone to replace it to the normal level. Adequate treatment gives the greatest benefit,”Dr. Jones said.

As more centers contribute data to the ABCD audit, Jones anticipates collecting clinical practice data on a variety of clinical parameters, including complications, total insulin dose, kidney function, and eventually cardiovascular outcomes.

In the meantime, he said, giving testosterone replacement to men with deficiency can be very rewarding for many reasons. “People feel better. Individual patients come back and say ‘thank you doctor, you’ve given me my life back.’ It’s not often you get that. And the compliance is excellent.”

Dr. Jones is a speaker for, advisory board member for, and/or travel grant recipient of Besins Healthcare, Grantss, Grunenthal, and Simple Pharma. Dr. Anawalt has no disclosures.

A version of this article first appeared on Medscape.com.

HAMBURG, GERMANY – Testosterone replacement therapy was associated with significant reductions in hemoglobin A1c at 1 and 2 years among men with type 2 diabetes, a multinational audit shows.

“If you have a patient with type 2 diabetes, sexual dysfunction, or fatigue, please consider checking their testosterone level. And if they fulfill criteria for testosterone deficiency and have had their [prostate-specific antigen] checked, consider a trial of treatment and follow them,” study lead author T. Hugh Jones, MD, consultant physician and endocrinologist at Barnsley (England) Hospital NHS Foundation Trust advised, speaking with this news organization.

Dr. Jones also urges clinicians worldwide to enter their patients’ data into the ABCD Testosterone Audit, which aims to identify long-term outcomes and predictors of response to testosterone replacement therapy.

Dr. Jones, who is also professor of andrology at the University of Sheffield, presented the preliminary data analysis at the annual meeting of the European Association for the Study of Diabetes.

Thus far, a total of 428 men with type 2 diabetes and hypogonadism are entered into the audit, from 34 centers in eight countries: the United Kingdom, Germany, Canada, Brazil, South Africa, New Zealand, Malaysia, and Vietnam. Among 121 of the men at 12 months, there was a drop in A1c from a baseline level of 71.27 mmol/mol (8.7%) to 61.26 mmol/mol (7.8%). Among 104 men at 24 months, the drop was from 71.4 mmol/mol (8.7%) to 55.97 mmol/mol (7.3%). Both decreases were significant (P < .001).

Prior data from Dr. Jones’ group showed that about 40% of men with type 2 diabetes have symptomatic testosterone deficiency. Testosterone deficiency is also associated with adverse effects on cardiovascular risk factors, bone health, muscle strength, sexual function, and psychological well-being, yet it is often overlooked, Dr. Jones noted.

“It’s not typically measured in routine clinical practice. ... Deficiency is very common, but a lot of practitioners don’t treat it and don’t ask about it. But in fact, treatment has very significant benefits for patients. ... We know from sildenafil (Viagra) studies that 60%of people who didn’t respond were testosterone deficient. After being given testosterone, they converted to Viagra responders,” he noted.

Regarding safety concerns, the recent findings from the TRAVERSE study, in which about 70% of participants had type 2 diabetes, demonstrated no increased cardiovascular risk. There was also no association with prostate cancer, although it’s important to monitor prostate-specific antigen in patients for the first year on testosterone replacement, Dr. Jones said.

Asked to comment, endocrinologist Bradley D. Anawalt, MD, chief of medicine at the University of Washington Medical Center, Seattle, told this news organization, “This ‘worldwide survey’ confirms many studies from around the world over the past 20 years. ... [T]he association is due to ‘reverse causation,’ in that diabetes type 2 and obesity lower testosterone concentrations. Weight loss of 5%-10% may raise testosterone concentrations in men with high body mass indices, large waist circumferences, and low blood testosterone concentrations.”

At the same time, Dr. Anawalt pointed to data suggesting that “[t]reatment of androgen deficiency may facilitate lifestyle measures in men with high [body mass indexes] and high risk of type 2 diabetes to prevent, or more likely delay, the development of type 2 diabetes.”

However, both Dr. Jones and Dr. Anawalt emphasized that testosterone therapy would not be expected to affect blood glucose levels or any other cardiometabolic parameters in men who are not testosterone deficient, regardless of diabetes status.

“It’s important when you give testosterone to replace it to the normal level. Adequate treatment gives the greatest benefit,”Dr. Jones said.

As more centers contribute data to the ABCD audit, Jones anticipates collecting clinical practice data on a variety of clinical parameters, including complications, total insulin dose, kidney function, and eventually cardiovascular outcomes.

In the meantime, he said, giving testosterone replacement to men with deficiency can be very rewarding for many reasons. “People feel better. Individual patients come back and say ‘thank you doctor, you’ve given me my life back.’ It’s not often you get that. And the compliance is excellent.”

Dr. Jones is a speaker for, advisory board member for, and/or travel grant recipient of Besins Healthcare, Grantss, Grunenthal, and Simple Pharma. Dr. Anawalt has no disclosures.

A version of this article first appeared on Medscape.com.

A process your body uses to stay warm in cool weather could one day lead to new therapies for obesity.

Scientists have, for the first time, mapped the precise nerve pathways that activate brown fat, or brown adipose tissue (BAT), a specialized fat that generates heat. Low temperatures kick brown fat into gear, helping the body keep its temperature and burning calories in the process.

“It has long been speculated that activating this type of fat may be useful in treating obesity and related metabolic conditions,” said Preethi Srikanthan, MD, an endocrinologist and professor of medicine who oversaw the research at the UCLA School of Medicine. “The challenge has been finding a way of selectively stimulating [it].”

Brown fat is different from the fat typically linked to obesity: the kind that accumulates around the belly, hips, and thighs. That’s white fat. White fat stores energy; brown fat burns it. That’s because brown fat cells have more mitochondria, a part of the cell that generates energy. 

After dissecting the necks of eight human cadavers, Dr. Srikanthan and her team traced the sympathetic nerve branches in the fat pad above the collarbone – where the largest depot of brown fat in adults is stored. They stained the nerves, took samples, and viewed them under a microscope. 

They found that nerves from brown fat traveled to the third and fourth cranial nerves of the brain, bundles of nerve fibers that control blinking and some eye movements.

In a previous case study, damage to these nerves appeared to block a chemical tracer from reaching brown fat. The evidence suggests that changing this nerve supply could alter brown fat activity, potentially leading to new treatments for obesity and metabolic diseases like type 2 diabetes, Dr. Srikanthan said.
 

A possible mechanism for Ozempic?

Brown fat has already been linked to at least one breakthrough in obesity treatment. Some evidence suggests that popular medications like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro) may affect brown fat activity. These belong to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists. They work by mimicking the hormone GLP-1, which is released in the gut and brain in response to eating glucose (sugary foods or drinks).

“GLP-1 agonists have been shown to increase [brown fat] activity in rodents and humans, but likely indirectly, via activation of specific regions in the brain,” explained Varman Samuel, MD, PhD, an associate professor of medicine at the Yale School of Medicine, New Haven, Conn., and chief of endocrinology for the VA Connecticut Healthcare System. 

The scientific literature is divided on this, but there is enough evidence to support further inquiry, Dr. Srikanthan said. Her team has begun a study to examine that link.
 

Opening the door to future obesity treatments

But their discovery means other new treatments could be on the horizon. 

Previous research had shown that the sympathetic nervous system drives brown fat activity. But now that the UCLA scientists have revealed the exact nerves connecting brown fat to the sympathetic nervous system, we could find ways to stimulate those pathways to activate brown fat – without stimulating the many organs (such as the heart and stomach) also connected to this vast network of nerves, Dr. Srikanthan said. 

Methods for doing that could include medication, electrical stimulation, or heat therapy, according to the study. 

Still, there is reason to temper expectations. “[Brown fat] depots, while highly metabolically active, are quite small,” Dr. Samuel said. “So, the overall contribution to whole-body energy balance in humans will likely be small.”

On the other hand, that prediction doesn’t account for what we don’t know. 

“We’re learning more about how tissues communicate with each other, beyond the release of hormones or metabolites,” Dr. Samuel said. Activating brown fat could trigger “signals that help coordinate whole-body energy metabolism.”

A version of this article first appeared on WebMD.com.

A process your body uses to stay warm in cool weather could one day lead to new therapies for obesity.

Scientists have, for the first time, mapped the precise nerve pathways that activate brown fat, or brown adipose tissue (BAT), a specialized fat that generates heat. Low temperatures kick brown fat into gear, helping the body keep its temperature and burning calories in the process.

“It has long been speculated that activating this type of fat may be useful in treating obesity and related metabolic conditions,” said Preethi Srikanthan, MD, an endocrinologist and professor of medicine who oversaw the research at the UCLA School of Medicine. “The challenge has been finding a way of selectively stimulating [it].”

Brown fat is different from the fat typically linked to obesity: the kind that accumulates around the belly, hips, and thighs. That’s white fat. White fat stores energy; brown fat burns it. That’s because brown fat cells have more mitochondria, a part of the cell that generates energy. 

After dissecting the necks of eight human cadavers, Dr. Srikanthan and her team traced the sympathetic nerve branches in the fat pad above the collarbone – where the largest depot of brown fat in adults is stored. They stained the nerves, took samples, and viewed them under a microscope. 

They found that nerves from brown fat traveled to the third and fourth cranial nerves of the brain, bundles of nerve fibers that control blinking and some eye movements.

In a previous case study, damage to these nerves appeared to block a chemical tracer from reaching brown fat. The evidence suggests that changing this nerve supply could alter brown fat activity, potentially leading to new treatments for obesity and metabolic diseases like type 2 diabetes, Dr. Srikanthan said.
 

A possible mechanism for Ozempic?

Brown fat has already been linked to at least one breakthrough in obesity treatment. Some evidence suggests that popular medications like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro) may affect brown fat activity. These belong to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists. They work by mimicking the hormone GLP-1, which is released in the gut and brain in response to eating glucose (sugary foods or drinks).

“GLP-1 agonists have been shown to increase [brown fat] activity in rodents and humans, but likely indirectly, via activation of specific regions in the brain,” explained Varman Samuel, MD, PhD, an associate professor of medicine at the Yale School of Medicine, New Haven, Conn., and chief of endocrinology for the VA Connecticut Healthcare System. 

The scientific literature is divided on this, but there is enough evidence to support further inquiry, Dr. Srikanthan said. Her team has begun a study to examine that link.
 

Opening the door to future obesity treatments

But their discovery means other new treatments could be on the horizon. 

Previous research had shown that the sympathetic nervous system drives brown fat activity. But now that the UCLA scientists have revealed the exact nerves connecting brown fat to the sympathetic nervous system, we could find ways to stimulate those pathways to activate brown fat – without stimulating the many organs (such as the heart and stomach) also connected to this vast network of nerves, Dr. Srikanthan said. 

Methods for doing that could include medication, electrical stimulation, or heat therapy, according to the study. 

Still, there is reason to temper expectations. “[Brown fat] depots, while highly metabolically active, are quite small,” Dr. Samuel said. “So, the overall contribution to whole-body energy balance in humans will likely be small.”

On the other hand, that prediction doesn’t account for what we don’t know. 

“We’re learning more about how tissues communicate with each other, beyond the release of hormones or metabolites,” Dr. Samuel said. Activating brown fat could trigger “signals that help coordinate whole-body energy metabolism.”

A version of this article first appeared on WebMD.com.

A process your body uses to stay warm in cool weather could one day lead to new therapies for obesity.

Scientists have, for the first time, mapped the precise nerve pathways that activate brown fat, or brown adipose tissue (BAT), a specialized fat that generates heat. Low temperatures kick brown fat into gear, helping the body keep its temperature and burning calories in the process.

“It has long been speculated that activating this type of fat may be useful in treating obesity and related metabolic conditions,” said Preethi Srikanthan, MD, an endocrinologist and professor of medicine who oversaw the research at the UCLA School of Medicine. “The challenge has been finding a way of selectively stimulating [it].”

Brown fat is different from the fat typically linked to obesity: the kind that accumulates around the belly, hips, and thighs. That’s white fat. White fat stores energy; brown fat burns it. That’s because brown fat cells have more mitochondria, a part of the cell that generates energy. 

After dissecting the necks of eight human cadavers, Dr. Srikanthan and her team traced the sympathetic nerve branches in the fat pad above the collarbone – where the largest depot of brown fat in adults is stored. They stained the nerves, took samples, and viewed them under a microscope. 

They found that nerves from brown fat traveled to the third and fourth cranial nerves of the brain, bundles of nerve fibers that control blinking and some eye movements.

In a previous case study, damage to these nerves appeared to block a chemical tracer from reaching brown fat. The evidence suggests that changing this nerve supply could alter brown fat activity, potentially leading to new treatments for obesity and metabolic diseases like type 2 diabetes, Dr. Srikanthan said.
 

A possible mechanism for Ozempic?

Brown fat has already been linked to at least one breakthrough in obesity treatment. Some evidence suggests that popular medications like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro) may affect brown fat activity. These belong to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists. They work by mimicking the hormone GLP-1, which is released in the gut and brain in response to eating glucose (sugary foods or drinks).

“GLP-1 agonists have been shown to increase [brown fat] activity in rodents and humans, but likely indirectly, via activation of specific regions in the brain,” explained Varman Samuel, MD, PhD, an associate professor of medicine at the Yale School of Medicine, New Haven, Conn., and chief of endocrinology for the VA Connecticut Healthcare System. 

The scientific literature is divided on this, but there is enough evidence to support further inquiry, Dr. Srikanthan said. Her team has begun a study to examine that link.
 

Opening the door to future obesity treatments

But their discovery means other new treatments could be on the horizon. 

Previous research had shown that the sympathetic nervous system drives brown fat activity. But now that the UCLA scientists have revealed the exact nerves connecting brown fat to the sympathetic nervous system, we could find ways to stimulate those pathways to activate brown fat – without stimulating the many organs (such as the heart and stomach) also connected to this vast network of nerves, Dr. Srikanthan said. 

Methods for doing that could include medication, electrical stimulation, or heat therapy, according to the study. 

Still, there is reason to temper expectations. “[Brown fat] depots, while highly metabolically active, are quite small,” Dr. Samuel said. “So, the overall contribution to whole-body energy balance in humans will likely be small.”

On the other hand, that prediction doesn’t account for what we don’t know. 

“We’re learning more about how tissues communicate with each other, beyond the release of hormones or metabolites,” Dr. Samuel said. Activating brown fat could trigger “signals that help coordinate whole-body energy metabolism.”

A version of this article first appeared on WebMD.com.

VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.

The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.

As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.

“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.

Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.

The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.

Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m². Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.

The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).

The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.

Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.

Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”

Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.

The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.

As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.

“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.

Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.

The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.

Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m². Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.

The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).

The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.

Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.

Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”

Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.

The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.

As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.

“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.

Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.

The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.

Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m². Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.

The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).

The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.

Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.

Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”

Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The prospect of remission of type 2 diabetes (T2D) has captured the hearts and minds of many patients with T2D and health care professionals, including myself.

I have changed my narrative when supporting my patients with T2D. I used to say that T2D is a progressive condition, but considering seminal recent evidence like the DiRECT trial, I now say that T2D can be a progressive condition. Through significant weight loss, patients can reverse it and achieve remission of T2D. This has given my patients hope that their T2D is no longer an inexorable condition. And hope, of course, is a powerful enabler of change.

However, the million-dollar question is whether remission of T2D can be maintained in the long term in the real-world setting of primary care, which is chiefly where T2D is managed.

I therefore relished the opportunity to attend a debate on this topic at the annual meeting of the European Association for the Study of Diabetes in Hamburg, Germany, between Roy Taylor, MD, principal investigator for the DiRECT study and professor of medicine and metabolism at the University of Newcastle, England, and Kamlesh Khunti, MD, PhD, professor of primary care diabetes at the University of Leicester, England.
 

Remarkable weight loss

Dr. Taylor powerfully recapitulated the initial results of the DiRECT study. T2D remission was achieved in 46% of participants who underwent a low-energy formula diet (around 850 calories daily) for 3-5 months. After 2 years’ follow-up, an impressive 36% of participants were still in remission. Dr. Taylor then discussed unpublished 5-year extension follow-up data of the DiRECT study. Average weight loss in the remaining intervention group was 6.1 kg. I echo Taylor’s sentiment that this finding is remarkable in the context of a dietary study.

Overall, 13% of participants were still in remission, and this cohort maintained an average weight loss of 8.9 kg. Dr. Taylor concluded that lasting remission of T2D is indeed feasible in a primary care setting.

Yet he acknowledged that although remission appears feasible in the longer term, it was not necessarily easy, or indeed possible, for everyone. He used a wonderful analogy about climbing Mount Everest: It is feasible, but not everyone can or wants to climb it. And even if you try, you might not reach the top.

This analogy perfectly encapsulates the challenges I have observed when my patients have striven for T2D remission. In my opinion, intensive weight management with a low-energy formula diet is not a panacea for T2D but another tool in our toolbox to offer patients.

He also described some “jaw-dropping” results regarding incidence of cancer: There were no cases of cancer in the intervention group during the 5-year period, but there were eight cases of cancer in the control group. The latter figure is consistent with published data for cancer incidence in patients with T2D and the body mass index (BMI) inclusion criteria for the DiRECT study (a BMI of 27-45 kg/m²). Obesity is an established risk factor for 13 types of cancer, and excess body fat entails an approximately 17% increased risk for cancer-specific mortality. This indeed is a powerful motivator to facilitate meaningful lifestyle change.

In primary care, we also need to be aware that most weight regain usually occurs secondary to a life event (for example, financial, family, or illness). We should reiterate to our patients that weight regain is not a failure; it is just part of life. Once the life event has passed, rapid weight loss can be attempted again. In the “rescue plans” that were integral to the DiRECT study, participants were offered further periods of total diet replacement, depending on quantity of weight gain. In fact, 50% of participants in DiRECT required rescue therapy, and their outcomes, reassuringly, were the same as the other 50%.

Dr. Taylor also quoted data from the ReTUNE study suggesting that weight regain was less of an issue for those with initial BMI of 21-27, and there is “more bang for your buck” in approaching remission of T2D in patients with lower BMI. The fact that people with normal or near-normal BMI can also reverse their T2D was also a game changer for my clinical practice; the concept of an individual or personal fat threshold that results in T2D offers a pragmatic explanation to patients with T2D who are frustrated by the lack of improvements in cardiometabolic parameters despite significant weight loss.

Finally, Dr. Taylor acknowledged the breadth of the definition of T2D remission: A1c < 48 mmol/mol at least 2 months off all antidiabetic medication. This definition includes A1c values within the “prediabetes” range: 42-47 mmol/mol.

He cited 10-year cardiovascular risk data driven by hypertension and dyslipidemia before significant weight loss and compared it with 10-year cardiovascular risk data after significant weight loss. Cardiovascular risk profile was more favorable after weight loss, compared with controls with prediabetes without weight loss, even though some of the intervention group who lost significant weight still had an A1c of 42-47 mmol/mol. Dr. Taylor suggested that we not label these individuals who have lost significant weight as having prediabetes. Instead “postdiabetes” should be preferred, because these patients had more favorable cardiovascular profiles.

This is a very important take-home message for primary care: prediabetes is more than just dysglycemia.
 

New terminology proposed

Dr. Khunti outlined a recent large, systematic review that concluded that the definition of T2D remission encompassed substantial heterogeneity. This heterogeneity complicates the interpretation of previous research on T2D remission and complicates the implementation of remission pathways into routine clinical practice. Furthermore, Dr. Khunti highlighted a recent consensus report on the definition and interpretation of remission in T2D that explicitly stated that the underlying pathophysiology of T2D is rarely normalized completely by interventions, thus reducing the possibility of lasting remission.

Dr. Khunti also challenged the cardiovascular benefits seen after T2D remission. Recent Danish registry data were presented, demonstrating a twofold increased risk for major adverse cardiovascular events over 5 years in individuals who achieved remission of T2D, but not on glucose-lowering drug therapy.

Adherence to strict dietary interventions in the longer term was also addressed. Diet-induced weight loss causes changes in circulating hormones such as ghrelin, glucose-dependent insulinotropic polypeptide (GIP), and leptin, which mediate appetite and drive hunger and an increased preference for energy-dense foods (that is, high-fat or sugary foods), all of which encourage weight regain. Dr. Khunti suggested that other interventions, such as glucagon-like peptide 1 (GLP-1) receptor agonists or bariatric surgery, specifically target some of these hormonal responses.

The challenges in recruitment and retention for lifestyle studies were also discussed; they reflect the challenges of behavioral programs in primary care. The DiRECT study had 20% participation of screened candidates and an attrition rate approaching 30%. The seminal Diabetes Prevention Program study and Finnish Diabetes Prevention Study had similar results. At a population level, individuals do not appear to want to participate in behavioral programs.

Dr. Khunti also warned that the review of annual care processes for diabetes is declining for patients who had achieved remission, possibly because of a false sense of reassurance among health care professionals. It is essential that all those in remission remain under at least annual follow-up, because there is still a risk for future microvascular and macrovascular complications, especially in the event of weight regain.

Dr. Khunti concluded by proposing new terminology for remission: remission of hyperglycemia or euglycemia, aiming for A1c < 48 mmol/mol with or without glucose-lowering therapy. I do agree with this; it reflects the zeitgeist of cardiorenal protective diabetes therapies and is analogous to rheumatoid arthritis, where remission is defined as no disease activity while on therapy. But one size does not fit all.

Sir William Osler’s words provide a fitting conclusion: “If it were not for the great variability among individuals, medicine might as well be a science and not an art.”

Dr. Fernando has disclosed that he has received speakers’ fees from Eli Lilly and Novo Nordisk.

Dr. Fernando is a general practitioner near Edinburgh, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education.

A version of this article first appeared on Medscape.com.

The prospect of remission of type 2 diabetes (T2D) has captured the hearts and minds of many patients with T2D and health care professionals, including myself.

I have changed my narrative when supporting my patients with T2D. I used to say that T2D is a progressive condition, but considering seminal recent evidence like the DiRECT trial, I now say that T2D can be a progressive condition. Through significant weight loss, patients can reverse it and achieve remission of T2D. This has given my patients hope that their T2D is no longer an inexorable condition. And hope, of course, is a powerful enabler of change.

However, the million-dollar question is whether remission of T2D can be maintained in the long term in the real-world setting of primary care, which is chiefly where T2D is managed.

I therefore relished the opportunity to attend a debate on this topic at the annual meeting of the European Association for the Study of Diabetes in Hamburg, Germany, between Roy Taylor, MD, principal investigator for the DiRECT study and professor of medicine and metabolism at the University of Newcastle, England, and Kamlesh Khunti, MD, PhD, professor of primary care diabetes at the University of Leicester, England.
 

Remarkable weight loss

Dr. Taylor powerfully recapitulated the initial results of the DiRECT study. T2D remission was achieved in 46% of participants who underwent a low-energy formula diet (around 850 calories daily) for 3-5 months. After 2 years’ follow-up, an impressive 36% of participants were still in remission. Dr. Taylor then discussed unpublished 5-year extension follow-up data of the DiRECT study. Average weight loss in the remaining intervention group was 6.1 kg. I echo Taylor’s sentiment that this finding is remarkable in the context of a dietary study.

Overall, 13% of participants were still in remission, and this cohort maintained an average weight loss of 8.9 kg. Dr. Taylor concluded that lasting remission of T2D is indeed feasible in a primary care setting.

Yet he acknowledged that although remission appears feasible in the longer term, it was not necessarily easy, or indeed possible, for everyone. He used a wonderful analogy about climbing Mount Everest: It is feasible, but not everyone can or wants to climb it. And even if you try, you might not reach the top.

This analogy perfectly encapsulates the challenges I have observed when my patients have striven for T2D remission. In my opinion, intensive weight management with a low-energy formula diet is not a panacea for T2D but another tool in our toolbox to offer patients.

He also described some “jaw-dropping” results regarding incidence of cancer: There were no cases of cancer in the intervention group during the 5-year period, but there were eight cases of cancer in the control group. The latter figure is consistent with published data for cancer incidence in patients with T2D and the body mass index (BMI) inclusion criteria for the DiRECT study (a BMI of 27-45 kg/m²). Obesity is an established risk factor for 13 types of cancer, and excess body fat entails an approximately 17% increased risk for cancer-specific mortality. This indeed is a powerful motivator to facilitate meaningful lifestyle change.

In primary care, we also need to be aware that most weight regain usually occurs secondary to a life event (for example, financial, family, or illness). We should reiterate to our patients that weight regain is not a failure; it is just part of life. Once the life event has passed, rapid weight loss can be attempted again. In the “rescue plans” that were integral to the DiRECT study, participants were offered further periods of total diet replacement, depending on quantity of weight gain. In fact, 50% of participants in DiRECT required rescue therapy, and their outcomes, reassuringly, were the same as the other 50%.

Dr. Taylor also quoted data from the ReTUNE study suggesting that weight regain was less of an issue for those with initial BMI of 21-27, and there is “more bang for your buck” in approaching remission of T2D in patients with lower BMI. The fact that people with normal or near-normal BMI can also reverse their T2D was also a game changer for my clinical practice; the concept of an individual or personal fat threshold that results in T2D offers a pragmatic explanation to patients with T2D who are frustrated by the lack of improvements in cardiometabolic parameters despite significant weight loss.

Finally, Dr. Taylor acknowledged the breadth of the definition of T2D remission: A1c < 48 mmol/mol at least 2 months off all antidiabetic medication. This definition includes A1c values within the “prediabetes” range: 42-47 mmol/mol.

He cited 10-year cardiovascular risk data driven by hypertension and dyslipidemia before significant weight loss and compared it with 10-year cardiovascular risk data after significant weight loss. Cardiovascular risk profile was more favorable after weight loss, compared with controls with prediabetes without weight loss, even though some of the intervention group who lost significant weight still had an A1c of 42-47 mmol/mol. Dr. Taylor suggested that we not label these individuals who have lost significant weight as having prediabetes. Instead “postdiabetes” should be preferred, because these patients had more favorable cardiovascular profiles.

This is a very important take-home message for primary care: prediabetes is more than just dysglycemia.
 

New terminology proposed

Dr. Khunti outlined a recent large, systematic review that concluded that the definition of T2D remission encompassed substantial heterogeneity. This heterogeneity complicates the interpretation of previous research on T2D remission and complicates the implementation of remission pathways into routine clinical practice. Furthermore, Dr. Khunti highlighted a recent consensus report on the definition and interpretation of remission in T2D that explicitly stated that the underlying pathophysiology of T2D is rarely normalized completely by interventions, thus reducing the possibility of lasting remission.

Dr. Khunti also challenged the cardiovascular benefits seen after T2D remission. Recent Danish registry data were presented, demonstrating a twofold increased risk for major adverse cardiovascular events over 5 years in individuals who achieved remission of T2D, but not on glucose-lowering drug therapy.

Adherence to strict dietary interventions in the longer term was also addressed. Diet-induced weight loss causes changes in circulating hormones such as ghrelin, glucose-dependent insulinotropic polypeptide (GIP), and leptin, which mediate appetite and drive hunger and an increased preference for energy-dense foods (that is, high-fat or sugary foods), all of which encourage weight regain. Dr. Khunti suggested that other interventions, such as glucagon-like peptide 1 (GLP-1) receptor agonists or bariatric surgery, specifically target some of these hormonal responses.

The challenges in recruitment and retention for lifestyle studies were also discussed; they reflect the challenges of behavioral programs in primary care. The DiRECT study had 20% participation of screened candidates and an attrition rate approaching 30%. The seminal Diabetes Prevention Program study and Finnish Diabetes Prevention Study had similar results. At a population level, individuals do not appear to want to participate in behavioral programs.

Dr. Khunti also warned that the review of annual care processes for diabetes is declining for patients who had achieved remission, possibly because of a false sense of reassurance among health care professionals. It is essential that all those in remission remain under at least annual follow-up, because there is still a risk for future microvascular and macrovascular complications, especially in the event of weight regain.

Dr. Khunti concluded by proposing new terminology for remission: remission of hyperglycemia or euglycemia, aiming for A1c < 48 mmol/mol with or without glucose-lowering therapy. I do agree with this; it reflects the zeitgeist of cardiorenal protective diabetes therapies and is analogous to rheumatoid arthritis, where remission is defined as no disease activity while on therapy. But one size does not fit all.

Sir William Osler’s words provide a fitting conclusion: “If it were not for the great variability among individuals, medicine might as well be a science and not an art.”

Dr. Fernando has disclosed that he has received speakers’ fees from Eli Lilly and Novo Nordisk.

Dr. Fernando is a general practitioner near Edinburgh, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education.

A version of this article first appeared on Medscape.com.

The prospect of remission of type 2 diabetes (T2D) has captured the hearts and minds of many patients with T2D and health care professionals, including myself.

I have changed my narrative when supporting my patients with T2D. I used to say that T2D is a progressive condition, but considering seminal recent evidence like the DiRECT trial, I now say that T2D can be a progressive condition. Through significant weight loss, patients can reverse it and achieve remission of T2D. This has given my patients hope that their T2D is no longer an inexorable condition. And hope, of course, is a powerful enabler of change.

However, the million-dollar question is whether remission of T2D can be maintained in the long term in the real-world setting of primary care, which is chiefly where T2D is managed.

I therefore relished the opportunity to attend a debate on this topic at the annual meeting of the European Association for the Study of Diabetes in Hamburg, Germany, between Roy Taylor, MD, principal investigator for the DiRECT study and professor of medicine and metabolism at the University of Newcastle, England, and Kamlesh Khunti, MD, PhD, professor of primary care diabetes at the University of Leicester, England.
 

Remarkable weight loss

Dr. Taylor powerfully recapitulated the initial results of the DiRECT study. T2D remission was achieved in 46% of participants who underwent a low-energy formula diet (around 850 calories daily) for 3-5 months. After 2 years’ follow-up, an impressive 36% of participants were still in remission. Dr. Taylor then discussed unpublished 5-year extension follow-up data of the DiRECT study. Average weight loss in the remaining intervention group was 6.1 kg. I echo Taylor’s sentiment that this finding is remarkable in the context of a dietary study.

Overall, 13% of participants were still in remission, and this cohort maintained an average weight loss of 8.9 kg. Dr. Taylor concluded that lasting remission of T2D is indeed feasible in a primary care setting.

Yet he acknowledged that although remission appears feasible in the longer term, it was not necessarily easy, or indeed possible, for everyone. He used a wonderful analogy about climbing Mount Everest: It is feasible, but not everyone can or wants to climb it. And even if you try, you might not reach the top.

This analogy perfectly encapsulates the challenges I have observed when my patients have striven for T2D remission. In my opinion, intensive weight management with a low-energy formula diet is not a panacea for T2D but another tool in our toolbox to offer patients.

He also described some “jaw-dropping” results regarding incidence of cancer: There were no cases of cancer in the intervention group during the 5-year period, but there were eight cases of cancer in the control group. The latter figure is consistent with published data for cancer incidence in patients with T2D and the body mass index (BMI) inclusion criteria for the DiRECT study (a BMI of 27-45 kg/m²). Obesity is an established risk factor for 13 types of cancer, and excess body fat entails an approximately 17% increased risk for cancer-specific mortality. This indeed is a powerful motivator to facilitate meaningful lifestyle change.

In primary care, we also need to be aware that most weight regain usually occurs secondary to a life event (for example, financial, family, or illness). We should reiterate to our patients that weight regain is not a failure; it is just part of life. Once the life event has passed, rapid weight loss can be attempted again. In the “rescue plans” that were integral to the DiRECT study, participants were offered further periods of total diet replacement, depending on quantity of weight gain. In fact, 50% of participants in DiRECT required rescue therapy, and their outcomes, reassuringly, were the same as the other 50%.

Dr. Taylor also quoted data from the ReTUNE study suggesting that weight regain was less of an issue for those with initial BMI of 21-27, and there is “more bang for your buck” in approaching remission of T2D in patients with lower BMI. The fact that people with normal or near-normal BMI can also reverse their T2D was also a game changer for my clinical practice; the concept of an individual or personal fat threshold that results in T2D offers a pragmatic explanation to patients with T2D who are frustrated by the lack of improvements in cardiometabolic parameters despite significant weight loss.

Finally, Dr. Taylor acknowledged the breadth of the definition of T2D remission: A1c < 48 mmol/mol at least 2 months off all antidiabetic medication. This definition includes A1c values within the “prediabetes” range: 42-47 mmol/mol.

He cited 10-year cardiovascular risk data driven by hypertension and dyslipidemia before significant weight loss and compared it with 10-year cardiovascular risk data after significant weight loss. Cardiovascular risk profile was more favorable after weight loss, compared with controls with prediabetes without weight loss, even though some of the intervention group who lost significant weight still had an A1c of 42-47 mmol/mol. Dr. Taylor suggested that we not label these individuals who have lost significant weight as having prediabetes. Instead “postdiabetes” should be preferred, because these patients had more favorable cardiovascular profiles.

This is a very important take-home message for primary care: prediabetes is more than just dysglycemia.
 

New terminology proposed

Dr. Khunti outlined a recent large, systematic review that concluded that the definition of T2D remission encompassed substantial heterogeneity. This heterogeneity complicates the interpretation of previous research on T2D remission and complicates the implementation of remission pathways into routine clinical practice. Furthermore, Dr. Khunti highlighted a recent consensus report on the definition and interpretation of remission in T2D that explicitly stated that the underlying pathophysiology of T2D is rarely normalized completely by interventions, thus reducing the possibility of lasting remission.

Dr. Khunti also challenged the cardiovascular benefits seen after T2D remission. Recent Danish registry data were presented, demonstrating a twofold increased risk for major adverse cardiovascular events over 5 years in individuals who achieved remission of T2D, but not on glucose-lowering drug therapy.

Adherence to strict dietary interventions in the longer term was also addressed. Diet-induced weight loss causes changes in circulating hormones such as ghrelin, glucose-dependent insulinotropic polypeptide (GIP), and leptin, which mediate appetite and drive hunger and an increased preference for energy-dense foods (that is, high-fat or sugary foods), all of which encourage weight regain. Dr. Khunti suggested that other interventions, such as glucagon-like peptide 1 (GLP-1) receptor agonists or bariatric surgery, specifically target some of these hormonal responses.

The challenges in recruitment and retention for lifestyle studies were also discussed; they reflect the challenges of behavioral programs in primary care. The DiRECT study had 20% participation of screened candidates and an attrition rate approaching 30%. The seminal Diabetes Prevention Program study and Finnish Diabetes Prevention Study had similar results. At a population level, individuals do not appear to want to participate in behavioral programs.

Dr. Khunti also warned that the review of annual care processes for diabetes is declining for patients who had achieved remission, possibly because of a false sense of reassurance among health care professionals. It is essential that all those in remission remain under at least annual follow-up, because there is still a risk for future microvascular and macrovascular complications, especially in the event of weight regain.

Dr. Khunti concluded by proposing new terminology for remission: remission of hyperglycemia or euglycemia, aiming for A1c < 48 mmol/mol with or without glucose-lowering therapy. I do agree with this; it reflects the zeitgeist of cardiorenal protective diabetes therapies and is analogous to rheumatoid arthritis, where remission is defined as no disease activity while on therapy. But one size does not fit all.

Sir William Osler’s words provide a fitting conclusion: “If it were not for the great variability among individuals, medicine might as well be a science and not an art.”

Dr. Fernando has disclosed that he has received speakers’ fees from Eli Lilly and Novo Nordisk.

Dr. Fernando is a general practitioner near Edinburgh, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education.

A version of this article first appeared on Medscape.com.

Can busy primary care offices continue to care for patients with diabetes? No one would argue that it is involved and takes effort, and health care providers are bankrupt when it comes to sparing additional time for this chronic disease. With roughly 37 million people living with diabetes and 96 million with prediabetes or early type 2 diabetes, and just over 8,000 practicing endocrinologists in the United States, we all need to make time especially in primary care to provide insight and holistic care. With limited time and budget, how do we do this?

First, decide to be involved in caring for patients with diabetes. Diabetes is best managed by interprofessional care teams, so you’re not going it alone. These teams may include physicians; pharmacists; physician assistants; advanced practice nurses; registered nurses; certified diabetes care and education specialists (CDCES); dietitians; and other professionals such as social workers, behavioral health professionals, medical assistants, and community health workers. Know which professionals are available to serve on your team, either within your clinic or as a consultant, and reach out to them to share the care and ease the burden. Remember to refer to these professionals to reinforce the diabetes intervention message to the patient.

Second, incorporate “diabetes only” appointments into your schedule, allowing time to focus on current comprehensive diabetes treatment goals, barriers/inertia for care. Remember to have short-interval follow-up as needed to keep that patient engaged to achieve their targets. Instruct your office staff to create diabetes appointment templates and reminders to patients to bring diabetes-related technologies, medication lists, and diabetes questions to the appointment. When I implemented this change, my patients welcomed the focus on their diabetes health, and they knew we were prioritizing this disease that they have for a lifetime. These appointments did not take away from their other conditions; rather, they often reminded me to stay focused on their diabetes and associated coconditions. 

Taking the time to establish efficient workflows before implementing diabetes care saves countless hours later and immediately maximizes health care provider–patient interactions. Assign specific staff duties and expectations related to diabetes appointments, such as downloading diabetes technology, medication reconciliation, laboratory data, point-of-care hemoglobin A1c, basic foot exam, and patient goals for diabetes care. This allows the prescriber to focus on the glycemic, cardiologic, renal, and metabolic goals and overcome the therapeutic inertia that plagues us all.

Incorporating diabetes-related technology into clinical practice can be a significant time-saver but requires initial onboarding. Set aside a few hours to create a technology clinic flow, and designate at least one team member to be responsible for obtaining patient data before, during, or after encounters. If possible, obtaining data ahead of the visit will enhance efficiency, allowing for meaningful discussion of blood glucose and lifestyle patterns. Diabetes technology reveals the gaps in care and enhances our ability to identify the areas where glycemic intervention is needed. In addition, it reveals the impact of food choices, activity level, stress, and medication adherence to the person living with diabetes. 

Finally, be proactive about therapeutic inertia. This is defined as a prescribers’ failure to intensify or deintensify a patient’s treatment when appropriate to do so. Causes of therapeutic inertia can be placed at the primary care physician level, including time constraints or inexperience in treating diabetes; the patient level, such as concerns about side effects or new treatment regimens; or a systemic level, such as availability of medications or their costs. Be real with yourself: We all have inertia and can identify areas to overcome. Never let inertia be traced back to you.

Not all inertia lives with the health care provider. Patients bring apprehension and concerns, have questions, and just want to share the frustrations associated with living their best life with the disease. Don’t assume that you know what your patients’ treatment barriers are; ask them. If you don’t have an answer, then note it and come up with one by the next follow-up. Remember that this is a chronic disease – a marathon, not a sprint. You don’t have to solve everything at one appointment; rather, keep the momentum going.

Let’s put this into clinical practice. For the next patient with diabetes who comes into your office, discuss with them your intention to prioritize their diabetes by having an appointment set aside to specifically focus on their individual goals and targets for their disease. Have the patient list any barriers and treatment goals they would like to review; flag your schedule to indicate it is a diabetes-only visit; and orient your staff to reconcile diabetes medications and record the patient’s last eye exam, urine albumin-to-creatinine ratio, A1c result, and blood glucose data. During this encounter, identify the patient’s personal targets for control, examine their feet, and review or order necessary laboratory metrics. Explore the patient-reported barriers and make inroads to remove or alleviate these. Advance treatment intervention, and schedule follow-up: every 4-6 weeks if the A1c is > 9%, every 2 months if it’s 7% to < 9%, and every 3-6 months if it’s < 7%. Utilize team diabetes care, such as CDCES referrals, dietitians, online resources, and community members, to help reinforce care and enhance engagement. 

We need to take steps in our clinical practice to make the necessary space to accommodate this pervasive disease affecting nearly one-third of our population. Take a moment to look up and determine what needs to be in place so that you can take care of the people in your practice with diabetes. Laying the groundwork for implementing diabetes-only appointments can be time-consuming, but establishing consistent procedures, developing efficient workflows, and clearly defining roles and responsibilities is well worth the effort. This solid foundation equips the office, health care providers, and staff to care for persons with diabetes and will be invaluable to ensure that time for this care is available in the day-to-day clinical practice.

A version of this article first appeared on Medscape.com.

Can busy primary care offices continue to care for patients with diabetes? No one would argue that it is involved and takes effort, and health care providers are bankrupt when it comes to sparing additional time for this chronic disease. With roughly 37 million people living with diabetes and 96 million with prediabetes or early type 2 diabetes, and just over 8,000 practicing endocrinologists in the United States, we all need to make time especially in primary care to provide insight and holistic care. With limited time and budget, how do we do this?

First, decide to be involved in caring for patients with diabetes. Diabetes is best managed by interprofessional care teams, so you’re not going it alone. These teams may include physicians; pharmacists; physician assistants; advanced practice nurses; registered nurses; certified diabetes care and education specialists (CDCES); dietitians; and other professionals such as social workers, behavioral health professionals, medical assistants, and community health workers. Know which professionals are available to serve on your team, either within your clinic or as a consultant, and reach out to them to share the care and ease the burden. Remember to refer to these professionals to reinforce the diabetes intervention message to the patient.

Second, incorporate “diabetes only” appointments into your schedule, allowing time to focus on current comprehensive diabetes treatment goals, barriers/inertia for care. Remember to have short-interval follow-up as needed to keep that patient engaged to achieve their targets. Instruct your office staff to create diabetes appointment templates and reminders to patients to bring diabetes-related technologies, medication lists, and diabetes questions to the appointment. When I implemented this change, my patients welcomed the focus on their diabetes health, and they knew we were prioritizing this disease that they have for a lifetime. These appointments did not take away from their other conditions; rather, they often reminded me to stay focused on their diabetes and associated coconditions. 

Taking the time to establish efficient workflows before implementing diabetes care saves countless hours later and immediately maximizes health care provider–patient interactions. Assign specific staff duties and expectations related to diabetes appointments, such as downloading diabetes technology, medication reconciliation, laboratory data, point-of-care hemoglobin A1c, basic foot exam, and patient goals for diabetes care. This allows the prescriber to focus on the glycemic, cardiologic, renal, and metabolic goals and overcome the therapeutic inertia that plagues us all.

Incorporating diabetes-related technology into clinical practice can be a significant time-saver but requires initial onboarding. Set aside a few hours to create a technology clinic flow, and designate at least one team member to be responsible for obtaining patient data before, during, or after encounters. If possible, obtaining data ahead of the visit will enhance efficiency, allowing for meaningful discussion of blood glucose and lifestyle patterns. Diabetes technology reveals the gaps in care and enhances our ability to identify the areas where glycemic intervention is needed. In addition, it reveals the impact of food choices, activity level, stress, and medication adherence to the person living with diabetes. 

Finally, be proactive about therapeutic inertia. This is defined as a prescribers’ failure to intensify or deintensify a patient’s treatment when appropriate to do so. Causes of therapeutic inertia can be placed at the primary care physician level, including time constraints or inexperience in treating diabetes; the patient level, such as concerns about side effects or new treatment regimens; or a systemic level, such as availability of medications or their costs. Be real with yourself: We all have inertia and can identify areas to overcome. Never let inertia be traced back to you.

Not all inertia lives with the health care provider. Patients bring apprehension and concerns, have questions, and just want to share the frustrations associated with living their best life with the disease. Don’t assume that you know what your patients’ treatment barriers are; ask them. If you don’t have an answer, then note it and come up with one by the next follow-up. Remember that this is a chronic disease – a marathon, not a sprint. You don’t have to solve everything at one appointment; rather, keep the momentum going.

Let’s put this into clinical practice. For the next patient with diabetes who comes into your office, discuss with them your intention to prioritize their diabetes by having an appointment set aside to specifically focus on their individual goals and targets for their disease. Have the patient list any barriers and treatment goals they would like to review; flag your schedule to indicate it is a diabetes-only visit; and orient your staff to reconcile diabetes medications and record the patient’s last eye exam, urine albumin-to-creatinine ratio, A1c result, and blood glucose data. During this encounter, identify the patient’s personal targets for control, examine their feet, and review or order necessary laboratory metrics. Explore the patient-reported barriers and make inroads to remove or alleviate these. Advance treatment intervention, and schedule follow-up: every 4-6 weeks if the A1c is > 9%, every 2 months if it’s 7% to < 9%, and every 3-6 months if it’s < 7%. Utilize team diabetes care, such as CDCES referrals, dietitians, online resources, and community members, to help reinforce care and enhance engagement. 

We need to take steps in our clinical practice to make the necessary space to accommodate this pervasive disease affecting nearly one-third of our population. Take a moment to look up and determine what needs to be in place so that you can take care of the people in your practice with diabetes. Laying the groundwork for implementing diabetes-only appointments can be time-consuming, but establishing consistent procedures, developing efficient workflows, and clearly defining roles and responsibilities is well worth the effort. This solid foundation equips the office, health care providers, and staff to care for persons with diabetes and will be invaluable to ensure that time for this care is available in the day-to-day clinical practice.

A version of this article first appeared on Medscape.com.

Can busy primary care offices continue to care for patients with diabetes? No one would argue that it is involved and takes effort, and health care providers are bankrupt when it comes to sparing additional time for this chronic disease. With roughly 37 million people living with diabetes and 96 million with prediabetes or early type 2 diabetes, and just over 8,000 practicing endocrinologists in the United States, we all need to make time especially in primary care to provide insight and holistic care. With limited time and budget, how do we do this?

First, decide to be involved in caring for patients with diabetes. Diabetes is best managed by interprofessional care teams, so you’re not going it alone. These teams may include physicians; pharmacists; physician assistants; advanced practice nurses; registered nurses; certified diabetes care and education specialists (CDCES); dietitians; and other professionals such as social workers, behavioral health professionals, medical assistants, and community health workers. Know which professionals are available to serve on your team, either within your clinic or as a consultant, and reach out to them to share the care and ease the burden. Remember to refer to these professionals to reinforce the diabetes intervention message to the patient.

Second, incorporate “diabetes only” appointments into your schedule, allowing time to focus on current comprehensive diabetes treatment goals, barriers/inertia for care. Remember to have short-interval follow-up as needed to keep that patient engaged to achieve their targets. Instruct your office staff to create diabetes appointment templates and reminders to patients to bring diabetes-related technologies, medication lists, and diabetes questions to the appointment. When I implemented this change, my patients welcomed the focus on their diabetes health, and they knew we were prioritizing this disease that they have for a lifetime. These appointments did not take away from their other conditions; rather, they often reminded me to stay focused on their diabetes and associated coconditions. 

Taking the time to establish efficient workflows before implementing diabetes care saves countless hours later and immediately maximizes health care provider–patient interactions. Assign specific staff duties and expectations related to diabetes appointments, such as downloading diabetes technology, medication reconciliation, laboratory data, point-of-care hemoglobin A1c, basic foot exam, and patient goals for diabetes care. This allows the prescriber to focus on the glycemic, cardiologic, renal, and metabolic goals and overcome the therapeutic inertia that plagues us all.

Incorporating diabetes-related technology into clinical practice can be a significant time-saver but requires initial onboarding. Set aside a few hours to create a technology clinic flow, and designate at least one team member to be responsible for obtaining patient data before, during, or after encounters. If possible, obtaining data ahead of the visit will enhance efficiency, allowing for meaningful discussion of blood glucose and lifestyle patterns. Diabetes technology reveals the gaps in care and enhances our ability to identify the areas where glycemic intervention is needed. In addition, it reveals the impact of food choices, activity level, stress, and medication adherence to the person living with diabetes. 

Finally, be proactive about therapeutic inertia. This is defined as a prescribers’ failure to intensify or deintensify a patient’s treatment when appropriate to do so. Causes of therapeutic inertia can be placed at the primary care physician level, including time constraints or inexperience in treating diabetes; the patient level, such as concerns about side effects or new treatment regimens; or a systemic level, such as availability of medications or their costs. Be real with yourself: We all have inertia and can identify areas to overcome. Never let inertia be traced back to you.

Not all inertia lives with the health care provider. Patients bring apprehension and concerns, have questions, and just want to share the frustrations associated with living their best life with the disease. Don’t assume that you know what your patients’ treatment barriers are; ask them. If you don’t have an answer, then note it and come up with one by the next follow-up. Remember that this is a chronic disease – a marathon, not a sprint. You don’t have to solve everything at one appointment; rather, keep the momentum going.

Let’s put this into clinical practice. For the next patient with diabetes who comes into your office, discuss with them your intention to prioritize their diabetes by having an appointment set aside to specifically focus on their individual goals and targets for their disease. Have the patient list any barriers and treatment goals they would like to review; flag your schedule to indicate it is a diabetes-only visit; and orient your staff to reconcile diabetes medications and record the patient’s last eye exam, urine albumin-to-creatinine ratio, A1c result, and blood glucose data. During this encounter, identify the patient’s personal targets for control, examine their feet, and review or order necessary laboratory metrics. Explore the patient-reported barriers and make inroads to remove or alleviate these. Advance treatment intervention, and schedule follow-up: every 4-6 weeks if the A1c is > 9%, every 2 months if it’s 7% to < 9%, and every 3-6 months if it’s < 7%. Utilize team diabetes care, such as CDCES referrals, dietitians, online resources, and community members, to help reinforce care and enhance engagement. 

We need to take steps in our clinical practice to make the necessary space to accommodate this pervasive disease affecting nearly one-third of our population. Take a moment to look up and determine what needs to be in place so that you can take care of the people in your practice with diabetes. Laying the groundwork for implementing diabetes-only appointments can be time-consuming, but establishing consistent procedures, developing efficient workflows, and clearly defining roles and responsibilities is well worth the effort. This solid foundation equips the office, health care providers, and staff to care for persons with diabetes and will be invaluable to ensure that time for this care is available in the day-to-day clinical practice.

A version of this article first appeared on Medscape.com.

The issue of earlier classification of medical conditions – known as “diagnosis creep” – is leading to many patients becoming eligible for treatments at earlier stages in their disease course, without those treatments having been validated in those particular groups.

This concern has been highlighted recently in the atrial fibrillation (AF) field, with the recent change in the definition of hypertension in the United States at lower levels of blood pressure causing a lot more patients to become eligible for oral anticoagulation at an earlier stage in their AF course.

U.S. researchers analyzed data from 316,388 patients with AF from the National Cardiovascular Data Registry Practice Innovation and Clinical Excellence outpatient quality improvement registry, and found that at 36 months’ follow-up, 83.5% of patients met the new 130/80 mm Hg definition of hypertension, while only 53.3% met the previous 140/90 mm Hg definition.

The diagnosis of hypertension gives 1 point in the CHA2DS2-VASc score, which is used to determine risk in AF patients, those with scores of 2 or more being eligible for oral anticoagulation.

The researchers report that in patients with an index CHA2DS2-VASc score of 1 (before the hypertension diagnosis), at 36 months, 83% fulfilled the 130/80 mm Hg definition of hypertension while the 140/90 mm Hg definition was met by only 50%, giving a large increase in the number of patients who could qualify for oral anticoagulation therapy.

“While the definition of hypertension has changed in response to landmark clinical trials, CHA2DS2-VASc was validated using an older hypertension definition, with limited ambulatory blood pressure monitoring and higher blood pressure goals for treatment,” the authors state.

“Now, patients with AF will meet the CHA2DS2-VASc threshold for oral anticoagulation earlier in their disease course. However, it is not known if patients with scores of 1 or 2 using the new hypertension definition have sufficient stroke risk to offset the bleeding risk of oral anticoagulation and will receive net clinical benefit,” they point out.

This study was published online as a research letter in JAMA Network Open.

Senior author of the report, Mintu Turakhia, MD, Stanford (Calif.) University/iRhythm Technologies Inc., said AF is a good example of how “diagnosis creep” may lead to patients receiving inappropriate treatment.

“Risk scores derived when risk variables were described in one way are starting to be applied based on a diagnosis made in a totally different way,” he said in an interview. “Diagnosis creep is a problem everywhere in medicine. The goal of this study was to quantify what this means for the new definition of hypertension in the context of risk scoring AF patients for anticoagulation treatment. We are calling attention to this issue so clinicians are aware of possible implications.”

Dr. Turakhia explained that the CHA2DS2-VASc score was formulated based on claims data so there was a record of hypertension on the clinical encounter. That hypertension diagnosis would have been based on the old definition of 140/90 mm Hg.

“But now we apply a label of hypertension in the office every time someone has a measurement of elevated blood pressure – treated or untreated – and the blood pressure threshold for a hypertension diagnosis has changed to 130/80 mm Hg,” he said. “We are asking what this means for risk stratification scores such as CHA2DS2-VASc, and how do we quantify what that means for anticoagulation eligibility?”

He said that while identifying hypertension at lower blood pressures may be beneficial with regard to starting antihypertensive treatment earlier with a consequent reduction in cardiovascular outcomes, when this also affects risk scores that determine treatment for other conditions, as is the case for AF, the case is not so clear.

Dr. Turakhia pointed out that with AF, there are additional factors causing diagnosis creep, including earlier detection of AF and identification of shorter episodes due to the use of higher sensitivity tools to detect abnormal rhythms.

“What about the patient who has been identified as having AF based on just a few seconds found on monitoring and who is aged 65 (so just over the age threshold for 1 point on the CHA2DS2-VASc score)?” he asked. “Now we’re going to throw in hypertension with a blood pressure measurement just over 130/80 mm Hg, and they will be eligible for anticoagulation.”

Dr. Turakhia noted that in addition to earlier classification of hypertension, other conditions contributing to the CHA2DS2-VASc score are also being detected earlier, including diabetes and reduced ejection fractions that are considered heart failure.

“I worry about the sum of the parts. We don’t know if the risk score performs equally well when we’re using these different thresholds. We have to be careful that we are not exposing patients to the bleeding risks of anticoagulation unnecessarily. There is a clear issue here,” he said.
 

What should clinicians do?

In a comment, Gregory Lip, MD, chair of cardiovascular medicine at the University of Liverpool, England, who helped develop the CHA2DS2-VASc score, said clinicians needed to think more broadly when considering hypertension as a risk factor for the score.

He points out that if a patient had a history of hypertension but is now controlled to below 130/80 mm Hg, they would still be considered to be at risk per the CHA2DS2-VASc score.

And for patients without a history of hypertension, and who have a current blood pressure measurement of around 130/80 mm Hg, Dr. Lip advises that it would be premature to diagnose hypertension immediately.

“Hypertension is not a yes/no diagnosis. If you look at the relationship between blood pressure and risk of stroke, it is like a continual dose-response. It doesn’t mean that at 129/79 there is no stroke risk but that at 130/80 there is a stroke risk. It’s not like that,” he said.

“I wouldn’t make a diagnosis on a one-off blood pressure measurement. I would want to monitor that patient and get them to do home measurements,” he commented. “If someone constantly has levels around that 130/80 mm Hg, I don’t necessarily rush in with a definite diagnosis of hypertension and start drug treatment. I would look at lifestyle first. And in such patients, I wouldn’t give them the 1 point for hypertension on the CHA2DS2-VASc score.”

Dr. Lip points out that a hypertension diagnosis is not just about blood pressure numbers. “We have to assess the patients much more completely before giving them a diagnosis and consider factors such as whether there is evidence of hypertension-related end-organ damage, and if lifestyle issues have been addressed.”
 

Are new risk scores needed?

Dr. Turakhia agreed that clinicians need to look at the bigger picture, but he also suggested that new risk scores may need to be developed.

“All of us in the medical community need to think about whether we should be recalibrating risk prediction with more contemporary evidence – based on our ability to detect disease now,” he commented.

“This could even be a different risk score altogether, possibly incorporating a wider range of parameters or perhaps incorporating machine learning. That’s really the question we need to be asking ourselves,” Dr. Turakhia added.

Dr. Lip noted that there are many stroke risk factors and only those that are most common and have been well validated go into clinical risk scores such as CHA2DS2-VASc.

“These risks scores are by design simplifications, and only have modest predictive value for identifying patients at high risk of stroke. You can always improve on clinical risk scores by adding in other variables,” he said. “There are some risk scores in AF with 26 variables. But the practical application of these more complex scores can be difficult in clinical practice. These risks scores are meant to be simple so that they can be used by busy clinicians in the outpatient clinic or on a ward round. It is not easy to input 26 different variables.”

He also noted that many guidelines are now veering away from categorizing patients at high, medium, or low risk of stroke, which he refers to as “artificial” classifications. “There is now more of a default position that patients should receive stroke prevention normally with a DOAC [direct oral anticoagulant] unless they are low risk.”

Dr. Turakhia agreed that it is imperative to look at the bigger picture when identifying AF patients for anticoagulation. “We have to be careful not to take things at face value. It is more important than ever to use clinical judgment to avoid overtreatment in borderline situations,” he concluded.

This study was supported by the American College of Cardiology Foundation’s National Cardiovascular Data Registry. Dr. Turakhia reported employment from iRhythm Technologies; equity from AliveCor, Connect America, Evidently, and Forward; grants from U.S. Food and Drug Administration, American Heart Association, Bayer, Sanofi, Gilead, and Bristol Myers Squibb; and personal fees from Pfizer and JAMA Cardiology (prior associate editor) outside the submitted work. Dr. Lip has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The issue of earlier classification of medical conditions – known as “diagnosis creep” – is leading to many patients becoming eligible for treatments at earlier stages in their disease course, without those treatments having been validated in those particular groups.

This concern has been highlighted recently in the atrial fibrillation (AF) field, with the recent change in the definition of hypertension in the United States at lower levels of blood pressure causing a lot more patients to become eligible for oral anticoagulation at an earlier stage in their AF course.

U.S. researchers analyzed data from 316,388 patients with AF from the National Cardiovascular Data Registry Practice Innovation and Clinical Excellence outpatient quality improvement registry, and found that at 36 months’ follow-up, 83.5% of patients met the new 130/80 mm Hg definition of hypertension, while only 53.3% met the previous 140/90 mm Hg definition.

The diagnosis of hypertension gives 1 point in the CHA2DS2-VASc score, which is used to determine risk in AF patients, those with scores of 2 or more being eligible for oral anticoagulation.

The researchers report that in patients with an index CHA2DS2-VASc score of 1 (before the hypertension diagnosis), at 36 months, 83% fulfilled the 130/80 mm Hg definition of hypertension while the 140/90 mm Hg definition was met by only 50%, giving a large increase in the number of patients who could qualify for oral anticoagulation therapy.

“While the definition of hypertension has changed in response to landmark clinical trials, CHA2DS2-VASc was validated using an older hypertension definition, with limited ambulatory blood pressure monitoring and higher blood pressure goals for treatment,” the authors state.

“Now, patients with AF will meet the CHA2DS2-VASc threshold for oral anticoagulation earlier in their disease course. However, it is not known if patients with scores of 1 or 2 using the new hypertension definition have sufficient stroke risk to offset the bleeding risk of oral anticoagulation and will receive net clinical benefit,” they point out.

This study was published online as a research letter in JAMA Network Open.

Senior author of the report, Mintu Turakhia, MD, Stanford (Calif.) University/iRhythm Technologies Inc., said AF is a good example of how “diagnosis creep” may lead to patients receiving inappropriate treatment.

“Risk scores derived when risk variables were described in one way are starting to be applied based on a diagnosis made in a totally different way,” he said in an interview. “Diagnosis creep is a problem everywhere in medicine. The goal of this study was to quantify what this means for the new definition of hypertension in the context of risk scoring AF patients for anticoagulation treatment. We are calling attention to this issue so clinicians are aware of possible implications.”

Dr. Turakhia explained that the CHA2DS2-VASc score was formulated based on claims data so there was a record of hypertension on the clinical encounter. That hypertension diagnosis would have been based on the old definition of 140/90 mm Hg.

“But now we apply a label of hypertension in the office every time someone has a measurement of elevated blood pressure – treated or untreated – and the blood pressure threshold for a hypertension diagnosis has changed to 130/80 mm Hg,” he said. “We are asking what this means for risk stratification scores such as CHA2DS2-VASc, and how do we quantify what that means for anticoagulation eligibility?”

He said that while identifying hypertension at lower blood pressures may be beneficial with regard to starting antihypertensive treatment earlier with a consequent reduction in cardiovascular outcomes, when this also affects risk scores that determine treatment for other conditions, as is the case for AF, the case is not so clear.

Dr. Turakhia pointed out that with AF, there are additional factors causing diagnosis creep, including earlier detection of AF and identification of shorter episodes due to the use of higher sensitivity tools to detect abnormal rhythms.

“What about the patient who has been identified as having AF based on just a few seconds found on monitoring and who is aged 65 (so just over the age threshold for 1 point on the CHA2DS2-VASc score)?” he asked. “Now we’re going to throw in hypertension with a blood pressure measurement just over 130/80 mm Hg, and they will be eligible for anticoagulation.”

Dr. Turakhia noted that in addition to earlier classification of hypertension, other conditions contributing to the CHA2DS2-VASc score are also being detected earlier, including diabetes and reduced ejection fractions that are considered heart failure.

“I worry about the sum of the parts. We don’t know if the risk score performs equally well when we’re using these different thresholds. We have to be careful that we are not exposing patients to the bleeding risks of anticoagulation unnecessarily. There is a clear issue here,” he said.
 

What should clinicians do?

In a comment, Gregory Lip, MD, chair of cardiovascular medicine at the University of Liverpool, England, who helped develop the CHA2DS2-VASc score, said clinicians needed to think more broadly when considering hypertension as a risk factor for the score.

He points out that if a patient had a history of hypertension but is now controlled to below 130/80 mm Hg, they would still be considered to be at risk per the CHA2DS2-VASc score.

And for patients without a history of hypertension, and who have a current blood pressure measurement of around 130/80 mm Hg, Dr. Lip advises that it would be premature to diagnose hypertension immediately.

“Hypertension is not a yes/no diagnosis. If you look at the relationship between blood pressure and risk of stroke, it is like a continual dose-response. It doesn’t mean that at 129/79 there is no stroke risk but that at 130/80 there is a stroke risk. It’s not like that,” he said.

“I wouldn’t make a diagnosis on a one-off blood pressure measurement. I would want to monitor that patient and get them to do home measurements,” he commented. “If someone constantly has levels around that 130/80 mm Hg, I don’t necessarily rush in with a definite diagnosis of hypertension and start drug treatment. I would look at lifestyle first. And in such patients, I wouldn’t give them the 1 point for hypertension on the CHA2DS2-VASc score.”

Dr. Lip points out that a hypertension diagnosis is not just about blood pressure numbers. “We have to assess the patients much more completely before giving them a diagnosis and consider factors such as whether there is evidence of hypertension-related end-organ damage, and if lifestyle issues have been addressed.”
 

Are new risk scores needed?

Dr. Turakhia agreed that clinicians need to look at the bigger picture, but he also suggested that new risk scores may need to be developed.

“All of us in the medical community need to think about whether we should be recalibrating risk prediction with more contemporary evidence – based on our ability to detect disease now,” he commented.

“This could even be a different risk score altogether, possibly incorporating a wider range of parameters or perhaps incorporating machine learning. That’s really the question we need to be asking ourselves,” Dr. Turakhia added.

Dr. Lip noted that there are many stroke risk factors and only those that are most common and have been well validated go into clinical risk scores such as CHA2DS2-VASc.

“These risks scores are by design simplifications, and only have modest predictive value for identifying patients at high risk of stroke. You can always improve on clinical risk scores by adding in other variables,” he said. “There are some risk scores in AF with 26 variables. But the practical application of these more complex scores can be difficult in clinical practice. These risks scores are meant to be simple so that they can be used by busy clinicians in the outpatient clinic or on a ward round. It is not easy to input 26 different variables.”

He also noted that many guidelines are now veering away from categorizing patients at high, medium, or low risk of stroke, which he refers to as “artificial” classifications. “There is now more of a default position that patients should receive stroke prevention normally with a DOAC [direct oral anticoagulant] unless they are low risk.”

Dr. Turakhia agreed that it is imperative to look at the bigger picture when identifying AF patients for anticoagulation. “We have to be careful not to take things at face value. It is more important than ever to use clinical judgment to avoid overtreatment in borderline situations,” he concluded.

This study was supported by the American College of Cardiology Foundation’s National Cardiovascular Data Registry. Dr. Turakhia reported employment from iRhythm Technologies; equity from AliveCor, Connect America, Evidently, and Forward; grants from U.S. Food and Drug Administration, American Heart Association, Bayer, Sanofi, Gilead, and Bristol Myers Squibb; and personal fees from Pfizer and JAMA Cardiology (prior associate editor) outside the submitted work. Dr. Lip has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The issue of earlier classification of medical conditions – known as “diagnosis creep” – is leading to many patients becoming eligible for treatments at earlier stages in their disease course, without those treatments having been validated in those particular groups.

This concern has been highlighted recently in the atrial fibrillation (AF) field, with the recent change in the definition of hypertension in the United States at lower levels of blood pressure causing a lot more patients to become eligible for oral anticoagulation at an earlier stage in their AF course.

U.S. researchers analyzed data from 316,388 patients with AF from the National Cardiovascular Data Registry Practice Innovation and Clinical Excellence outpatient quality improvement registry, and found that at 36 months’ follow-up, 83.5% of patients met the new 130/80 mm Hg definition of hypertension, while only 53.3% met the previous 140/90 mm Hg definition.

The diagnosis of hypertension gives 1 point in the CHA2DS2-VASc score, which is used to determine risk in AF patients, those with scores of 2 or more being eligible for oral anticoagulation.

The researchers report that in patients with an index CHA2DS2-VASc score of 1 (before the hypertension diagnosis), at 36 months, 83% fulfilled the 130/80 mm Hg definition of hypertension while the 140/90 mm Hg definition was met by only 50%, giving a large increase in the number of patients who could qualify for oral anticoagulation therapy.

“While the definition of hypertension has changed in response to landmark clinical trials, CHA2DS2-VASc was validated using an older hypertension definition, with limited ambulatory blood pressure monitoring and higher blood pressure goals for treatment,” the authors state.

“Now, patients with AF will meet the CHA2DS2-VASc threshold for oral anticoagulation earlier in their disease course. However, it is not known if patients with scores of 1 or 2 using the new hypertension definition have sufficient stroke risk to offset the bleeding risk of oral anticoagulation and will receive net clinical benefit,” they point out.

This study was published online as a research letter in JAMA Network Open.

Senior author of the report, Mintu Turakhia, MD, Stanford (Calif.) University/iRhythm Technologies Inc., said AF is a good example of how “diagnosis creep” may lead to patients receiving inappropriate treatment.

“Risk scores derived when risk variables were described in one way are starting to be applied based on a diagnosis made in a totally different way,” he said in an interview. “Diagnosis creep is a problem everywhere in medicine. The goal of this study was to quantify what this means for the new definition of hypertension in the context of risk scoring AF patients for anticoagulation treatment. We are calling attention to this issue so clinicians are aware of possible implications.”

Dr. Turakhia explained that the CHA2DS2-VASc score was formulated based on claims data so there was a record of hypertension on the clinical encounter. That hypertension diagnosis would have been based on the old definition of 140/90 mm Hg.

“But now we apply a label of hypertension in the office every time someone has a measurement of elevated blood pressure – treated or untreated – and the blood pressure threshold for a hypertension diagnosis has changed to 130/80 mm Hg,” he said. “We are asking what this means for risk stratification scores such as CHA2DS2-VASc, and how do we quantify what that means for anticoagulation eligibility?”

He said that while identifying hypertension at lower blood pressures may be beneficial with regard to starting antihypertensive treatment earlier with a consequent reduction in cardiovascular outcomes, when this also affects risk scores that determine treatment for other conditions, as is the case for AF, the case is not so clear.

Dr. Turakhia pointed out that with AF, there are additional factors causing diagnosis creep, including earlier detection of AF and identification of shorter episodes due to the use of higher sensitivity tools to detect abnormal rhythms.

“What about the patient who has been identified as having AF based on just a few seconds found on monitoring and who is aged 65 (so just over the age threshold for 1 point on the CHA2DS2-VASc score)?” he asked. “Now we’re going to throw in hypertension with a blood pressure measurement just over 130/80 mm Hg, and they will be eligible for anticoagulation.”

Dr. Turakhia noted that in addition to earlier classification of hypertension, other conditions contributing to the CHA2DS2-VASc score are also being detected earlier, including diabetes and reduced ejection fractions that are considered heart failure.

“I worry about the sum of the parts. We don’t know if the risk score performs equally well when we’re using these different thresholds. We have to be careful that we are not exposing patients to the bleeding risks of anticoagulation unnecessarily. There is a clear issue here,” he said.
 

What should clinicians do?

In a comment, Gregory Lip, MD, chair of cardiovascular medicine at the University of Liverpool, England, who helped develop the CHA2DS2-VASc score, said clinicians needed to think more broadly when considering hypertension as a risk factor for the score.

He points out that if a patient had a history of hypertension but is now controlled to below 130/80 mm Hg, they would still be considered to be at risk per the CHA2DS2-VASc score.

And for patients without a history of hypertension, and who have a current blood pressure measurement of around 130/80 mm Hg, Dr. Lip advises that it would be premature to diagnose hypertension immediately.

“Hypertension is not a yes/no diagnosis. If you look at the relationship between blood pressure and risk of stroke, it is like a continual dose-response. It doesn’t mean that at 129/79 there is no stroke risk but that at 130/80 there is a stroke risk. It’s not like that,” he said.

“I wouldn’t make a diagnosis on a one-off blood pressure measurement. I would want to monitor that patient and get them to do home measurements,” he commented. “If someone constantly has levels around that 130/80 mm Hg, I don’t necessarily rush in with a definite diagnosis of hypertension and start drug treatment. I would look at lifestyle first. And in such patients, I wouldn’t give them the 1 point for hypertension on the CHA2DS2-VASc score.”

Dr. Lip points out that a hypertension diagnosis is not just about blood pressure numbers. “We have to assess the patients much more completely before giving them a diagnosis and consider factors such as whether there is evidence of hypertension-related end-organ damage, and if lifestyle issues have been addressed.”
 

Are new risk scores needed?

Dr. Turakhia agreed that clinicians need to look at the bigger picture, but he also suggested that new risk scores may need to be developed.

“All of us in the medical community need to think about whether we should be recalibrating risk prediction with more contemporary evidence – based on our ability to detect disease now,” he commented.

“This could even be a different risk score altogether, possibly incorporating a wider range of parameters or perhaps incorporating machine learning. That’s really the question we need to be asking ourselves,” Dr. Turakhia added.

Dr. Lip noted that there are many stroke risk factors and only those that are most common and have been well validated go into clinical risk scores such as CHA2DS2-VASc.

“These risks scores are by design simplifications, and only have modest predictive value for identifying patients at high risk of stroke. You can always improve on clinical risk scores by adding in other variables,” he said. “There are some risk scores in AF with 26 variables. But the practical application of these more complex scores can be difficult in clinical practice. These risks scores are meant to be simple so that they can be used by busy clinicians in the outpatient clinic or on a ward round. It is not easy to input 26 different variables.”

He also noted that many guidelines are now veering away from categorizing patients at high, medium, or low risk of stroke, which he refers to as “artificial” classifications. “There is now more of a default position that patients should receive stroke prevention normally with a DOAC [direct oral anticoagulant] unless they are low risk.”

Dr. Turakhia agreed that it is imperative to look at the bigger picture when identifying AF patients for anticoagulation. “We have to be careful not to take things at face value. It is more important than ever to use clinical judgment to avoid overtreatment in borderline situations,” he concluded.

This study was supported by the American College of Cardiology Foundation’s National Cardiovascular Data Registry. Dr. Turakhia reported employment from iRhythm Technologies; equity from AliveCor, Connect America, Evidently, and Forward; grants from U.S. Food and Drug Administration, American Heart Association, Bayer, Sanofi, Gilead, and Bristol Myers Squibb; and personal fees from Pfizer and JAMA Cardiology (prior associate editor) outside the submitted work. Dr. Lip has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.