Osteoarthritis

TOPLINE:

MRI-derived abdominal adipose tissue is linked to chronic musculoskeletal pain in multiple sites. The association is stronger in women, suggesting sex differences in fat distribution and hormones.

METHODOLOGY:

• Researchers used data from the UK Biobank, a large population-based cohort study, to investigate the associations between MRI-measured abdominal adipose tissue and chronic musculoskeletal pain.
• A total of 32,409 participants (50.8% women; mean age, 55.0 ± 7.4 years) were included in the analysis, with abdominal MRI scans performed at two imaging visits.
• Pain in the neck/shoulder, back, hip, knee, or “all over the body” was assessed, and participants were categorized based on the number of chronic pain sites.
• Mixed-effects ordinal, multinomial, and logistic regression models were used to analyze the associations between visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and their ratio with chronic pain.

TAKEAWAY:

• According to the authors, there was a dose-response association between VAT, SAT, and their ratio with the number of chronic pain sites in both women and men.
• Higher levels of abdominal adipose tissue were associated with greater odds of reporting chronic pain in both sexes, with effect estimates being relatively larger in women.
• The researchers found that the VAT/SAT ratio was associated with the number of chronic pain sites and chronic pain in both sexes, reflecting differences in fat distribution and hormones.
• The study suggested that excessive abdominal adipose tissue may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain.

IN PRACTICE:

“Abdominal adipose tissue was associated with chronic musculoskeletal pain, suggesting that excessive and ectopic fat depositions may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain,” wrote the authors of the study.

SOURCE:

This study was led by Zemene Demelash Kifle, University of Tasmania Menzies Institute for Medical Research in Hobart, Australia. It was published online in Regional Anesthesia & Pain Medicine.

LIMITATIONS: 

The study’s limitations included the use of a pain questionnaire that did not assess pain severity, which limited the ability to examine the relationship between fat measures and pain severity. Additionally, MRI was conducted on only two occasions, which may have not captured patterns and fluctuations in chronic pain sites. The relatively small size of the imaging sample, compared with the original baseline sample limited the generalizability of the findings. The predominant White ethnicity of participants also limited the generalizability to diverse populations.

DISCLOSURES:

The study was supported by grants from the Australian National Health and Medical Research Council (NHMRC). Mr. Kifle disclosed receiving grants from the Australian NHMRC. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

MRI-derived abdominal adipose tissue is linked to chronic musculoskeletal pain in multiple sites. The association is stronger in women, suggesting sex differences in fat distribution and hormones.

METHODOLOGY:

• Researchers used data from the UK Biobank, a large population-based cohort study, to investigate the associations between MRI-measured abdominal adipose tissue and chronic musculoskeletal pain.
• A total of 32,409 participants (50.8% women; mean age, 55.0 ± 7.4 years) were included in the analysis, with abdominal MRI scans performed at two imaging visits.
• Pain in the neck/shoulder, back, hip, knee, or “all over the body” was assessed, and participants were categorized based on the number of chronic pain sites.
• Mixed-effects ordinal, multinomial, and logistic regression models were used to analyze the associations between visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and their ratio with chronic pain.

TAKEAWAY:

• According to the authors, there was a dose-response association between VAT, SAT, and their ratio with the number of chronic pain sites in both women and men.
• Higher levels of abdominal adipose tissue were associated with greater odds of reporting chronic pain in both sexes, with effect estimates being relatively larger in women.
• The researchers found that the VAT/SAT ratio was associated with the number of chronic pain sites and chronic pain in both sexes, reflecting differences in fat distribution and hormones.
• The study suggested that excessive abdominal adipose tissue may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain.

IN PRACTICE:

“Abdominal adipose tissue was associated with chronic musculoskeletal pain, suggesting that excessive and ectopic fat depositions may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain,” wrote the authors of the study.

SOURCE:

This study was led by Zemene Demelash Kifle, University of Tasmania Menzies Institute for Medical Research in Hobart, Australia. It was published online in Regional Anesthesia & Pain Medicine.

LIMITATIONS: 

The study’s limitations included the use of a pain questionnaire that did not assess pain severity, which limited the ability to examine the relationship between fat measures and pain severity. Additionally, MRI was conducted on only two occasions, which may have not captured patterns and fluctuations in chronic pain sites. The relatively small size of the imaging sample, compared with the original baseline sample limited the generalizability of the findings. The predominant White ethnicity of participants also limited the generalizability to diverse populations.

DISCLOSURES:

The study was supported by grants from the Australian National Health and Medical Research Council (NHMRC). Mr. Kifle disclosed receiving grants from the Australian NHMRC. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

MRI-derived abdominal adipose tissue is linked to chronic musculoskeletal pain in multiple sites. The association is stronger in women, suggesting sex differences in fat distribution and hormones.

METHODOLOGY:

• Researchers used data from the UK Biobank, a large population-based cohort study, to investigate the associations between MRI-measured abdominal adipose tissue and chronic musculoskeletal pain.
• A total of 32,409 participants (50.8% women; mean age, 55.0 ± 7.4 years) were included in the analysis, with abdominal MRI scans performed at two imaging visits.
• Pain in the neck/shoulder, back, hip, knee, or “all over the body” was assessed, and participants were categorized based on the number of chronic pain sites.
• Mixed-effects ordinal, multinomial, and logistic regression models were used to analyze the associations between visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and their ratio with chronic pain.

TAKEAWAY:

• According to the authors, there was a dose-response association between VAT, SAT, and their ratio with the number of chronic pain sites in both women and men.
• Higher levels of abdominal adipose tissue were associated with greater odds of reporting chronic pain in both sexes, with effect estimates being relatively larger in women.
• The researchers found that the VAT/SAT ratio was associated with the number of chronic pain sites and chronic pain in both sexes, reflecting differences in fat distribution and hormones.
• The study suggested that excessive abdominal adipose tissue may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain.

IN PRACTICE:

“Abdominal adipose tissue was associated with chronic musculoskeletal pain, suggesting that excessive and ectopic fat depositions may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain,” wrote the authors of the study.

SOURCE:

This study was led by Zemene Demelash Kifle, University of Tasmania Menzies Institute for Medical Research in Hobart, Australia. It was published online in Regional Anesthesia & Pain Medicine.

LIMITATIONS: 

The study’s limitations included the use of a pain questionnaire that did not assess pain severity, which limited the ability to examine the relationship between fat measures and pain severity. Additionally, MRI was conducted on only two occasions, which may have not captured patterns and fluctuations in chronic pain sites. The relatively small size of the imaging sample, compared with the original baseline sample limited the generalizability of the findings. The predominant White ethnicity of participants also limited the generalizability to diverse populations.

DISCLOSURES:

The study was supported by grants from the Australian National Health and Medical Research Council (NHMRC). Mr. Kifle disclosed receiving grants from the Australian NHMRC. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Ultrasonography reveals tendon involvement in nearly 70% of the patients with hand osteoarthritis (OA), with no significant impact on hand function or pain. Tendon damage was more frequent in the flexor tendons, while tenosynovitis was more common in the extensor tendons.

METHODOLOGY:

• Tendon damage is commonly associated with radiographic damage in rheumatoid arthritis and is a typical finding in psoriatic arthritis; however, data on tendon involvement in hand OA are scarce.
• Researchers assessed tendon involvement, its impact on pain and hand function, and its association with radiographic features in hand OA.
• They conducted a cross-sectional, monocenter observational study including 86 patients with hand OA (mean age, 65.9 years; 87.2% women) and 23 age- and sex-matched control individuals without bony enlargement and hand pain at a tertiary center of rheumatic and musculoskeletal disease in Vienna.
• Clinical examination and ultrasonography were used to assess the extensor and flexor tendons of both hands for tenosynovitis and tendon damage.
• Participants completed the Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) questionnaire and the Moberg pickup test for the assessment of hand function, stiffness, and pain.

TAKEAWAY:

• Ultrasonography identified tendon involvement in a higher proportion of patients with hand OA than in control individuals (69.8% vs 8.7%; P < .01).
• In patients with hand OA, the flexor tendons were more commonly affected by tendon damage than the extensor tendons (2.1% vs 0.9%; P = .03), whereas tenosynovitis was more prevalent in the extensor tendons than in the flexor tendons (8.0% vs 0.6%; P < .001).
• No significant association was found between tendon involvement and hand function or self-reported pain.
• The sensitivity and specificity of clinical evaluation in identifying tendon involvement were 14.5% and 83.8%, respectively.

IN PRACTICE:

“Physicians treating patients with hand OA should keep the high prevalence of tendon involvement in mind,” the authors wrote. “In case of clinical suspicion, a sonographic examination should be performed. If tenosynovitis or tendon damage is detected, treatment may be tailored accordingly.”

SOURCE:

The study, led by Irina Gessl, MD, Department of Internal Medicine III, Medical University of Vienna in Austria, was published online on August 7, 2024, in Rheumatology.

LIMITATIONS: 

The study lacked a standardized clinical examination and a preferred method for detecting tenosynovitis and tendon damage. The lack of a separate evaluation of clinical tenderness in individual joints may have hindered a more comprehensive assessment of pain. The M-SACRAH questionnaire is validated for assessing the overall hand function in patients with hand OA and rheumatoid arthritis but not tendon involvement.

DISCLOSURES:

The Medical Scientific Fund of the Mayor of the City of Vienna supported the study. Some authors reported receiving personal fees, grants, royalties, or licenses and being part of speakers bureau for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE: 

Ultrasonography reveals tendon involvement in nearly 70% of the patients with hand osteoarthritis (OA), with no significant impact on hand function or pain. Tendon damage was more frequent in the flexor tendons, while tenosynovitis was more common in the extensor tendons.

METHODOLOGY:

• Tendon damage is commonly associated with radiographic damage in rheumatoid arthritis and is a typical finding in psoriatic arthritis; however, data on tendon involvement in hand OA are scarce.
• Researchers assessed tendon involvement, its impact on pain and hand function, and its association with radiographic features in hand OA.
• They conducted a cross-sectional, monocenter observational study including 86 patients with hand OA (mean age, 65.9 years; 87.2% women) and 23 age- and sex-matched control individuals without bony enlargement and hand pain at a tertiary center of rheumatic and musculoskeletal disease in Vienna.
• Clinical examination and ultrasonography were used to assess the extensor and flexor tendons of both hands for tenosynovitis and tendon damage.
• Participants completed the Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) questionnaire and the Moberg pickup test for the assessment of hand function, stiffness, and pain.

TAKEAWAY:

• Ultrasonography identified tendon involvement in a higher proportion of patients with hand OA than in control individuals (69.8% vs 8.7%; P < .01).
• In patients with hand OA, the flexor tendons were more commonly affected by tendon damage than the extensor tendons (2.1% vs 0.9%; P = .03), whereas tenosynovitis was more prevalent in the extensor tendons than in the flexor tendons (8.0% vs 0.6%; P < .001).
• No significant association was found between tendon involvement and hand function or self-reported pain.
• The sensitivity and specificity of clinical evaluation in identifying tendon involvement were 14.5% and 83.8%, respectively.

IN PRACTICE:

“Physicians treating patients with hand OA should keep the high prevalence of tendon involvement in mind,” the authors wrote. “In case of clinical suspicion, a sonographic examination should be performed. If tenosynovitis or tendon damage is detected, treatment may be tailored accordingly.”

SOURCE:

The study, led by Irina Gessl, MD, Department of Internal Medicine III, Medical University of Vienna in Austria, was published online on August 7, 2024, in Rheumatology.

LIMITATIONS: 

The study lacked a standardized clinical examination and a preferred method for detecting tenosynovitis and tendon damage. The lack of a separate evaluation of clinical tenderness in individual joints may have hindered a more comprehensive assessment of pain. The M-SACRAH questionnaire is validated for assessing the overall hand function in patients with hand OA and rheumatoid arthritis but not tendon involvement.

DISCLOSURES:

The Medical Scientific Fund of the Mayor of the City of Vienna supported the study. Some authors reported receiving personal fees, grants, royalties, or licenses and being part of speakers bureau for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE: 

Ultrasonography reveals tendon involvement in nearly 70% of the patients with hand osteoarthritis (OA), with no significant impact on hand function or pain. Tendon damage was more frequent in the flexor tendons, while tenosynovitis was more common in the extensor tendons.

METHODOLOGY:

• Tendon damage is commonly associated with radiographic damage in rheumatoid arthritis and is a typical finding in psoriatic arthritis; however, data on tendon involvement in hand OA are scarce.
• Researchers assessed tendon involvement, its impact on pain and hand function, and its association with radiographic features in hand OA.
• They conducted a cross-sectional, monocenter observational study including 86 patients with hand OA (mean age, 65.9 years; 87.2% women) and 23 age- and sex-matched control individuals without bony enlargement and hand pain at a tertiary center of rheumatic and musculoskeletal disease in Vienna.
• Clinical examination and ultrasonography were used to assess the extensor and flexor tendons of both hands for tenosynovitis and tendon damage.
• Participants completed the Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) questionnaire and the Moberg pickup test for the assessment of hand function, stiffness, and pain.

TAKEAWAY:

• Ultrasonography identified tendon involvement in a higher proportion of patients with hand OA than in control individuals (69.8% vs 8.7%; P < .01).
• In patients with hand OA, the flexor tendons were more commonly affected by tendon damage than the extensor tendons (2.1% vs 0.9%; P = .03), whereas tenosynovitis was more prevalent in the extensor tendons than in the flexor tendons (8.0% vs 0.6%; P < .001).
• No significant association was found between tendon involvement and hand function or self-reported pain.
• The sensitivity and specificity of clinical evaluation in identifying tendon involvement were 14.5% and 83.8%, respectively.

IN PRACTICE:

“Physicians treating patients with hand OA should keep the high prevalence of tendon involvement in mind,” the authors wrote. “In case of clinical suspicion, a sonographic examination should be performed. If tenosynovitis or tendon damage is detected, treatment may be tailored accordingly.”

SOURCE:

The study, led by Irina Gessl, MD, Department of Internal Medicine III, Medical University of Vienna in Austria, was published online on August 7, 2024, in Rheumatology.

LIMITATIONS: 

The study lacked a standardized clinical examination and a preferred method for detecting tenosynovitis and tendon damage. The lack of a separate evaluation of clinical tenderness in individual joints may have hindered a more comprehensive assessment of pain. The M-SACRAH questionnaire is validated for assessing the overall hand function in patients with hand OA and rheumatoid arthritis but not tendon involvement.

DISCLOSURES:

The Medical Scientific Fund of the Mayor of the City of Vienna supported the study. Some authors reported receiving personal fees, grants, royalties, or licenses and being part of speakers bureau for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

The antimetabolite and immunosuppressant methotrexate, taken orally and in addition to usual analgesia, alleviates pain in patients with knee osteoarthritis.

METHODOLOGY:

• Investigators conducted a phase 3 randomized controlled trial among 155 patients in the United Kingdom with painful radiographic knee osteoarthritis and an inadequate response to their current medication (PROMOTE trial).
• Patients were assigned to oral methotrexate once weekly (6-week escalation from 10 to 25 mg) or placebo for 12 months, added to usual analgesia.
• The main outcome was average knee pain at 6 months on a numerical rating scale from 0 to 10.

TAKEAWAY:

• At 6 months, mean scores for knee pain had decreased by 1.3 points in the methotrexate group and 0.6 points in the placebo group (difference by intention to treat, 0.79 points; P = .030).
• The former also saw greater benefit in terms of Western Ontario and McMaster Universities Osteoarthritis Index scores for stiffness (difference, 0.60 points; P = .045) and physical function (difference, 5.01 points; P = .008).
• Differences between groups were no longer significant at 12 months.
• Benefit of methotrexate appeared to be dose related.
• The groups were similar with respect to nausea and diarrhea; four serious adverse events (two per group) were deemed unrelated to study treatment.

IN PRACTICE:

“Further work is required to understand adequate methotrexate dosing, whether benefits are greater in those with elevated systemic inflammation levels, and to consider cost-effectiveness before introducing this therapy for a potentially large population,” the authors wrote.

SOURCE:

The study was led by Sarah R. Kingsbury, PhD, University of Leeds and National Institute for Health and Care Research Leeds Biomedical Research Centre, Leeds, England, and was published online in Annals of Internal Medicine.

LIMITATIONS:

Limitations included a decrease in methotrexate dose between 6 and 12 months, nonallowance of switching to subcutaneous drug for intolerance, and a lack of assessment of the effectiveness of blinding.

DISCLOSURES:

The study was funded by Versus Arthritis, a charity that supports people with arthritis. Some authors reported affiliations with Versus Arthritis and/or companies that develop drugs for arthritis.

A version of this article appeared on Medscape.com.

TOPLINE:

The antimetabolite and immunosuppressant methotrexate, taken orally and in addition to usual analgesia, alleviates pain in patients with knee osteoarthritis.

METHODOLOGY:

• Investigators conducted a phase 3 randomized controlled trial among 155 patients in the United Kingdom with painful radiographic knee osteoarthritis and an inadequate response to their current medication (PROMOTE trial).
• Patients were assigned to oral methotrexate once weekly (6-week escalation from 10 to 25 mg) or placebo for 12 months, added to usual analgesia.
• The main outcome was average knee pain at 6 months on a numerical rating scale from 0 to 10.

TAKEAWAY:

• At 6 months, mean scores for knee pain had decreased by 1.3 points in the methotrexate group and 0.6 points in the placebo group (difference by intention to treat, 0.79 points; P = .030).
• The former also saw greater benefit in terms of Western Ontario and McMaster Universities Osteoarthritis Index scores for stiffness (difference, 0.60 points; P = .045) and physical function (difference, 5.01 points; P = .008).
• Differences between groups were no longer significant at 12 months.
• Benefit of methotrexate appeared to be dose related.
• The groups were similar with respect to nausea and diarrhea; four serious adverse events (two per group) were deemed unrelated to study treatment.

IN PRACTICE:

“Further work is required to understand adequate methotrexate dosing, whether benefits are greater in those with elevated systemic inflammation levels, and to consider cost-effectiveness before introducing this therapy for a potentially large population,” the authors wrote.

SOURCE:

The study was led by Sarah R. Kingsbury, PhD, University of Leeds and National Institute for Health and Care Research Leeds Biomedical Research Centre, Leeds, England, and was published online in Annals of Internal Medicine.

LIMITATIONS:

Limitations included a decrease in methotrexate dose between 6 and 12 months, nonallowance of switching to subcutaneous drug for intolerance, and a lack of assessment of the effectiveness of blinding.

DISCLOSURES:

The study was funded by Versus Arthritis, a charity that supports people with arthritis. Some authors reported affiliations with Versus Arthritis and/or companies that develop drugs for arthritis.

A version of this article appeared on Medscape.com.

TOPLINE:

The antimetabolite and immunosuppressant methotrexate, taken orally and in addition to usual analgesia, alleviates pain in patients with knee osteoarthritis.

METHODOLOGY:

• Investigators conducted a phase 3 randomized controlled trial among 155 patients in the United Kingdom with painful radiographic knee osteoarthritis and an inadequate response to their current medication (PROMOTE trial).
• Patients were assigned to oral methotrexate once weekly (6-week escalation from 10 to 25 mg) or placebo for 12 months, added to usual analgesia.
• The main outcome was average knee pain at 6 months on a numerical rating scale from 0 to 10.

TAKEAWAY:

• At 6 months, mean scores for knee pain had decreased by 1.3 points in the methotrexate group and 0.6 points in the placebo group (difference by intention to treat, 0.79 points; P = .030).
• The former also saw greater benefit in terms of Western Ontario and McMaster Universities Osteoarthritis Index scores for stiffness (difference, 0.60 points; P = .045) and physical function (difference, 5.01 points; P = .008).
• Differences between groups were no longer significant at 12 months.
• Benefit of methotrexate appeared to be dose related.
• The groups were similar with respect to nausea and diarrhea; four serious adverse events (two per group) were deemed unrelated to study treatment.

IN PRACTICE:

“Further work is required to understand adequate methotrexate dosing, whether benefits are greater in those with elevated systemic inflammation levels, and to consider cost-effectiveness before introducing this therapy for a potentially large population,” the authors wrote.

SOURCE:

The study was led by Sarah R. Kingsbury, PhD, University of Leeds and National Institute for Health and Care Research Leeds Biomedical Research Centre, Leeds, England, and was published online in Annals of Internal Medicine.

LIMITATIONS:

Limitations included a decrease in methotrexate dose between 6 and 12 months, nonallowance of switching to subcutaneous drug for intolerance, and a lack of assessment of the effectiveness of blinding.

DISCLOSURES:

The study was funded by Versus Arthritis, a charity that supports people with arthritis. Some authors reported affiliations with Versus Arthritis and/or companies that develop drugs for arthritis.

A version of this article appeared on Medscape.com.

TOPLINE:

The estimated number of US adults who consumed at least one of the six most frequently reported hepatotoxic botanicals in the last 30 days is similar to the number of patients prescribed potentially hepatotoxic drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs) and simvastatin.

METHODOLOGY:

• Herbal and dietary supplements (HDS) are an increasingly common source of drug hepatotoxicity cases, but their prevalence and the reasons for their use among the general population are uncertain.
• This survey study evaluated nationally representative data from 9685 adults (mean age, 47.5 years; 51.8% women) enrolled in the National Health and Nutrition Examination Survey (NHANES) between January 2017 and March 2020.
• Participants reported their use of HDS and prescription drugs through personal interviews for a 30-day period prior to the survey date.
• Researchers compared the clinical features and baseline demographic characteristics of users of six potentially hepatotoxic botanicals (ie, turmeric, green tea, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha) with those of nonusers.
• The prevalence of use of these at-risk botanicals was compared with that of widely prescribed potentially hepatotoxic medications, including NSAIDs, simvastatin, and sertraline.

TAKEAWAY:

• In the cohort of 9685 participants, 4.7% of individuals reported consumption of at least one of the six potentially hepatotoxic botanicals in the past 30 days, with turmeric being the most common, followed by green tea.
• Extrapolating the survey data, researchers estimated that 15.6 million US adults use at least one of these six botanicals, which is comparable to the number of those prescribed potentially hepatotoxic drugs, including NSAIDs (14.8 million) and simvastatin (14.0 million). Sertraline use was lower (7.7 million).
• Most individuals used these botanicals without the recommendation of their healthcare provider.
• Those using botanicals were more likely to be older (adjusted odds ratio [aOR], 2.36; P = .04 for 40-59 years; aOR, 3.96; P = .001 for ≥ 60 years), to have some college education (aOR, 4.78; P < .001), and to have arthritis (aOR, 2.27; P < .001) than nonusers.
• The most common reasons for using any of these six potential hepatotoxic botanicals were to improve or maintain health or to prevent health problems or boost immunity.

IN PRACTICE:

“In light of the lack of regulatory oversight on the manufacturing and testing of botanical products, it is recommended that clinicians obtain a full medication and HDS use history when evaluating patients with unexplained symptoms or liver test abnormalities,” the authors wrote.

SOURCE:

The study, led by Alisa Likhitsup, MD, MPH, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, was published online in JAMA Network Open. 

LIMITATIONS:

The survey response rate was low at 43.9% for adults aged ≥ 20 years. As NHANES is a cross-sectional study, the causal relationship between consumption of the six botanicals of interest and the development of liver injury could not be determined. The use of HDS products and medications was self-reported in NHANES and not independently verified using source documents. 

DISCLOSURES:

This study did not report any source of funding. Two authors declared receiving grants from pharmaceutical companies outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

The estimated number of US adults who consumed at least one of the six most frequently reported hepatotoxic botanicals in the last 30 days is similar to the number of patients prescribed potentially hepatotoxic drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs) and simvastatin.

METHODOLOGY:

• Herbal and dietary supplements (HDS) are an increasingly common source of drug hepatotoxicity cases, but their prevalence and the reasons for their use among the general population are uncertain.
• This survey study evaluated nationally representative data from 9685 adults (mean age, 47.5 years; 51.8% women) enrolled in the National Health and Nutrition Examination Survey (NHANES) between January 2017 and March 2020.
• Participants reported their use of HDS and prescription drugs through personal interviews for a 30-day period prior to the survey date.
• Researchers compared the clinical features and baseline demographic characteristics of users of six potentially hepatotoxic botanicals (ie, turmeric, green tea, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha) with those of nonusers.
• The prevalence of use of these at-risk botanicals was compared with that of widely prescribed potentially hepatotoxic medications, including NSAIDs, simvastatin, and sertraline.

TAKEAWAY:

• In the cohort of 9685 participants, 4.7% of individuals reported consumption of at least one of the six potentially hepatotoxic botanicals in the past 30 days, with turmeric being the most common, followed by green tea.
• Extrapolating the survey data, researchers estimated that 15.6 million US adults use at least one of these six botanicals, which is comparable to the number of those prescribed potentially hepatotoxic drugs, including NSAIDs (14.8 million) and simvastatin (14.0 million). Sertraline use was lower (7.7 million).
• Most individuals used these botanicals without the recommendation of their healthcare provider.
• Those using botanicals were more likely to be older (adjusted odds ratio [aOR], 2.36; P = .04 for 40-59 years; aOR, 3.96; P = .001 for ≥ 60 years), to have some college education (aOR, 4.78; P < .001), and to have arthritis (aOR, 2.27; P < .001) than nonusers.
• The most common reasons for using any of these six potential hepatotoxic botanicals were to improve or maintain health or to prevent health problems or boost immunity.

IN PRACTICE:

“In light of the lack of regulatory oversight on the manufacturing and testing of botanical products, it is recommended that clinicians obtain a full medication and HDS use history when evaluating patients with unexplained symptoms or liver test abnormalities,” the authors wrote.

SOURCE:

The study, led by Alisa Likhitsup, MD, MPH, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, was published online in JAMA Network Open. 

LIMITATIONS:

The survey response rate was low at 43.9% for adults aged ≥ 20 years. As NHANES is a cross-sectional study, the causal relationship between consumption of the six botanicals of interest and the development of liver injury could not be determined. The use of HDS products and medications was self-reported in NHANES and not independently verified using source documents. 

DISCLOSURES:

This study did not report any source of funding. Two authors declared receiving grants from pharmaceutical companies outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

The estimated number of US adults who consumed at least one of the six most frequently reported hepatotoxic botanicals in the last 30 days is similar to the number of patients prescribed potentially hepatotoxic drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs) and simvastatin.

METHODOLOGY:

• Herbal and dietary supplements (HDS) are an increasingly common source of drug hepatotoxicity cases, but their prevalence and the reasons for their use among the general population are uncertain.
• This survey study evaluated nationally representative data from 9685 adults (mean age, 47.5 years; 51.8% women) enrolled in the National Health and Nutrition Examination Survey (NHANES) between January 2017 and March 2020.
• Participants reported their use of HDS and prescription drugs through personal interviews for a 30-day period prior to the survey date.
• Researchers compared the clinical features and baseline demographic characteristics of users of six potentially hepatotoxic botanicals (ie, turmeric, green tea, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha) with those of nonusers.
• The prevalence of use of these at-risk botanicals was compared with that of widely prescribed potentially hepatotoxic medications, including NSAIDs, simvastatin, and sertraline.

TAKEAWAY:

• In the cohort of 9685 participants, 4.7% of individuals reported consumption of at least one of the six potentially hepatotoxic botanicals in the past 30 days, with turmeric being the most common, followed by green tea.
• Extrapolating the survey data, researchers estimated that 15.6 million US adults use at least one of these six botanicals, which is comparable to the number of those prescribed potentially hepatotoxic drugs, including NSAIDs (14.8 million) and simvastatin (14.0 million). Sertraline use was lower (7.7 million).
• Most individuals used these botanicals without the recommendation of their healthcare provider.
• Those using botanicals were more likely to be older (adjusted odds ratio [aOR], 2.36; P = .04 for 40-59 years; aOR, 3.96; P = .001 for ≥ 60 years), to have some college education (aOR, 4.78; P < .001), and to have arthritis (aOR, 2.27; P < .001) than nonusers.
• The most common reasons for using any of these six potential hepatotoxic botanicals were to improve or maintain health or to prevent health problems or boost immunity.

IN PRACTICE:

“In light of the lack of regulatory oversight on the manufacturing and testing of botanical products, it is recommended that clinicians obtain a full medication and HDS use history when evaluating patients with unexplained symptoms or liver test abnormalities,” the authors wrote.

SOURCE:

The study, led by Alisa Likhitsup, MD, MPH, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, was published online in JAMA Network Open. 

LIMITATIONS:

The survey response rate was low at 43.9% for adults aged ≥ 20 years. As NHANES is a cross-sectional study, the causal relationship between consumption of the six botanicals of interest and the development of liver injury could not be determined. The use of HDS products and medications was self-reported in NHANES and not independently verified using source documents. 

DISCLOSURES:

This study did not report any source of funding. Two authors declared receiving grants from pharmaceutical companies outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

About 40% of patients with osteoarthritis (OA) and 36% with rheumatoid arthritis (RA) screened positive for anxiety, depression, and/or fibromyalgia as part of routine visits to an academic medical center, and these comorbidities were linked to poorer patient status measures, highlighting the need for routine screening in clinical practice. 

METHODOLOGY:

• This retrospective cross-sectional study analyzed the prevalence of anxiety, depression, and fibromyalgia in 366 patients with OA (mean age, 66.6 years) and 488 patients with RA (mean age, 56.9 years) who were in routine care at an academic center from 2011 to 2022.
• All participants were required to have complete Multidimensional Health Assessment Questionnaire (MDHAQ) data available for the analysis.
• The MDHAQ included indices to assess the overall patient status and screen for anxiety, depression, and fibromyalgia.
• The overall patient status was measured using the Routine Assessment of Patient Index Data 3 (RAPID3), which comprised the physical function, pain, and patient global scores.
• The prevalence of each comorbidity and its association with patient status was analyzed using unadjusted and age-adjusted odds ratios (ORs) and 95% CIs.

TAKEAWAY:

• Among the patients with OA, 40.4% were screened positive for at least one of the three indices indicating patient distress (anxiety, depression, and fibromyalgia). Among patients with RA, the proportion was 36.3%.
• Among the patients who screened positive for at least one index, about 20% screened positive for all three indices related to anxiety, depression, and fibromyalgia.
• In patients with OA, a poorer patient status (RAPID3, ≥ 12 vs < 12) increased the likelihood of anxiety (OR, 3.93; 95% CI, 2.24-7.23), depression (OR, 3.79; 95% CI, 2.01-7.73), and fibromyalgia (OR, 6.70; 95% CI, 3.36-14.99).
• Similarly, the odds of all three comorbidities increased in the patients with RA who had worsened patient status.

IN PRACTICE:

“Screening for [anxiety, depression, and/or fibromyalgia] can be incorporated feasibly into routine clinical care using a single MDHAQ to better inform health professionals concerning patient status, prognosis, and response to treatments,” the authors wrote.

SOURCE:

The study was led by Juan Schmukler, MD, Rush University Medical Center, Chicago, and was published online on July 16, 2024, in ACR Open Rheumatology. 

LIMITATIONS:

The analyses were cross-sectional, and whether anxiety, depression, and fibromyalgia had preceded or followed the onset of OA or RA was not known. Information on the clinical variables associated with anxiety, depression, and fibromyalgia, such as body mass index, medication history, and other comorbid conditions, was not available. All the patients were seen at a single rheumatology site, which may have limited the generalizability of the observations. 

DISCLOSURES:

This study did not disclose any sources of funding. One author disclosed receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author reported numerous financial relationships with companies in the medical industry, and another reported holding a copyright and trademark on MDHAQ and RAPID3. 

This article was created using several editorial tools, including AI, as a part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About 40% of patients with osteoarthritis (OA) and 36% with rheumatoid arthritis (RA) screened positive for anxiety, depression, and/or fibromyalgia as part of routine visits to an academic medical center, and these comorbidities were linked to poorer patient status measures, highlighting the need for routine screening in clinical practice. 

METHODOLOGY:

• This retrospective cross-sectional study analyzed the prevalence of anxiety, depression, and fibromyalgia in 366 patients with OA (mean age, 66.6 years) and 488 patients with RA (mean age, 56.9 years) who were in routine care at an academic center from 2011 to 2022.
• All participants were required to have complete Multidimensional Health Assessment Questionnaire (MDHAQ) data available for the analysis.
• The MDHAQ included indices to assess the overall patient status and screen for anxiety, depression, and fibromyalgia.
• The overall patient status was measured using the Routine Assessment of Patient Index Data 3 (RAPID3), which comprised the physical function, pain, and patient global scores.
• The prevalence of each comorbidity and its association with patient status was analyzed using unadjusted and age-adjusted odds ratios (ORs) and 95% CIs.

TAKEAWAY:

• Among the patients with OA, 40.4% were screened positive for at least one of the three indices indicating patient distress (anxiety, depression, and fibromyalgia). Among patients with RA, the proportion was 36.3%.
• Among the patients who screened positive for at least one index, about 20% screened positive for all three indices related to anxiety, depression, and fibromyalgia.
• In patients with OA, a poorer patient status (RAPID3, ≥ 12 vs < 12) increased the likelihood of anxiety (OR, 3.93; 95% CI, 2.24-7.23), depression (OR, 3.79; 95% CI, 2.01-7.73), and fibromyalgia (OR, 6.70; 95% CI, 3.36-14.99).
• Similarly, the odds of all three comorbidities increased in the patients with RA who had worsened patient status.

IN PRACTICE:

“Screening for [anxiety, depression, and/or fibromyalgia] can be incorporated feasibly into routine clinical care using a single MDHAQ to better inform health professionals concerning patient status, prognosis, and response to treatments,” the authors wrote.

SOURCE:

The study was led by Juan Schmukler, MD, Rush University Medical Center, Chicago, and was published online on July 16, 2024, in ACR Open Rheumatology. 

LIMITATIONS:

The analyses were cross-sectional, and whether anxiety, depression, and fibromyalgia had preceded or followed the onset of OA or RA was not known. Information on the clinical variables associated with anxiety, depression, and fibromyalgia, such as body mass index, medication history, and other comorbid conditions, was not available. All the patients were seen at a single rheumatology site, which may have limited the generalizability of the observations. 

DISCLOSURES:

This study did not disclose any sources of funding. One author disclosed receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author reported numerous financial relationships with companies in the medical industry, and another reported holding a copyright and trademark on MDHAQ and RAPID3. 

This article was created using several editorial tools, including AI, as a part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About 40% of patients with osteoarthritis (OA) and 36% with rheumatoid arthritis (RA) screened positive for anxiety, depression, and/or fibromyalgia as part of routine visits to an academic medical center, and these comorbidities were linked to poorer patient status measures, highlighting the need for routine screening in clinical practice. 

METHODOLOGY:

• This retrospective cross-sectional study analyzed the prevalence of anxiety, depression, and fibromyalgia in 366 patients with OA (mean age, 66.6 years) and 488 patients with RA (mean age, 56.9 years) who were in routine care at an academic center from 2011 to 2022.
• All participants were required to have complete Multidimensional Health Assessment Questionnaire (MDHAQ) data available for the analysis.
• The MDHAQ included indices to assess the overall patient status and screen for anxiety, depression, and fibromyalgia.
• The overall patient status was measured using the Routine Assessment of Patient Index Data 3 (RAPID3), which comprised the physical function, pain, and patient global scores.
• The prevalence of each comorbidity and its association with patient status was analyzed using unadjusted and age-adjusted odds ratios (ORs) and 95% CIs.

TAKEAWAY:

• Among the patients with OA, 40.4% were screened positive for at least one of the three indices indicating patient distress (anxiety, depression, and fibromyalgia). Among patients with RA, the proportion was 36.3%.
• Among the patients who screened positive for at least one index, about 20% screened positive for all three indices related to anxiety, depression, and fibromyalgia.
• In patients with OA, a poorer patient status (RAPID3, ≥ 12 vs < 12) increased the likelihood of anxiety (OR, 3.93; 95% CI, 2.24-7.23), depression (OR, 3.79; 95% CI, 2.01-7.73), and fibromyalgia (OR, 6.70; 95% CI, 3.36-14.99).
• Similarly, the odds of all three comorbidities increased in the patients with RA who had worsened patient status.

IN PRACTICE:

“Screening for [anxiety, depression, and/or fibromyalgia] can be incorporated feasibly into routine clinical care using a single MDHAQ to better inform health professionals concerning patient status, prognosis, and response to treatments,” the authors wrote.

SOURCE:

The study was led by Juan Schmukler, MD, Rush University Medical Center, Chicago, and was published online on July 16, 2024, in ACR Open Rheumatology. 

LIMITATIONS:

The analyses were cross-sectional, and whether anxiety, depression, and fibromyalgia had preceded or followed the onset of OA or RA was not known. Information on the clinical variables associated with anxiety, depression, and fibromyalgia, such as body mass index, medication history, and other comorbid conditions, was not available. All the patients were seen at a single rheumatology site, which may have limited the generalizability of the observations. 

DISCLOSURES:

This study did not disclose any sources of funding. One author disclosed receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author reported numerous financial relationships with companies in the medical industry, and another reported holding a copyright and trademark on MDHAQ and RAPID3. 

This article was created using several editorial tools, including AI, as a part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

People with knee osteoarthritis and symptoms for less than 1 year benefit more from exercise therapy than do those with longer symptom duration, especially when long-term outcomes are considered.

METHODOLOGY:

• Researchers conducted an individual participant data meta-analysis using data from the OA Trial Bank, including 1769 participants (mean age, 65.1 years; 66% women) with knee osteoarthritis from 10 randomized controlled trials.
• The participants were categorized on the basis of their symptom duration: ≤ 1 year, > 1 and ≤ 2 years, and > 2 years.
• This study included an exercise therapy group comprising land- and water-based therapeutic exercise interventions and a control group comprising no exercise or sham treatment.
• The primary outcomes were self-reported pain and physical function, standardized to a 0-100 scale, at short-term (closest to 3 months) and long-term (closest to 12 months) follow-ups.

TAKEAWAY:

• The overall pain and physical function associated with osteoarthritis improved in the exercise therapy group at both short- and long-term follow-ups compared with in the control group.
• Exercise therapy led to a greater improvement in short-term (mean difference [MD], −3.57; P = .028) and long-term (MD, −8.33; P < .001) pain among participants with a symptom duration ≤ 1 year vs > 1 year.
• Similarly, those with a symptom duration ≤ 2 years vs > 2 years who underwent exercise therapy showed greater benefits in terms of short-term (P = .001) and long-term (P < .001) pain.
• Exercise therapy improved long-term physical function in those with a symptom duration ≤ 1 year vs > 1 year (MD, −5.46; P = .005) and ≤ 2 years vs > 2 years (MD, −4.56; P = .001).

IN PRACTICE:

“Exercise should be encouraged as early as possible once symptoms emerge in the disease process to take advantage of its effects in potentially [slowing] disease progression within the suggested ‘window of opportunity,’ ” the authors wrote.

SOURCE:

The study was led by Marienke van Middelkoop, PhD, Erasmus MC Medical University, Rotterdam, the Netherlands. It was published online in Osteoarthritis and Cartilage.

LIMITATIONS:

The dataset of most studies included in the meta-analysis lacked information on the radiographic severity of osteoarthritis. The relatively short follow-up time hindered interpreting the impact of exercise on the long-term progression of osteoarthritis. The reliance on patient recall for recording symptom duration may have led to misclassification.

DISCLOSURES:

The Netherlands Organisation for Health Research and Development supported this study. Three authors received funding from the Dutch Arthritis Society for the program grant Center of Excellence “OA prevention and early treatment – OA Pearl.” One author declared receiving royalties for the UpToDate knee osteoarthritis clinical guidelines.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

People with knee osteoarthritis and symptoms for less than 1 year benefit more from exercise therapy than do those with longer symptom duration, especially when long-term outcomes are considered.

METHODOLOGY:

• Researchers conducted an individual participant data meta-analysis using data from the OA Trial Bank, including 1769 participants (mean age, 65.1 years; 66% women) with knee osteoarthritis from 10 randomized controlled trials.
• The participants were categorized on the basis of their symptom duration: ≤ 1 year, > 1 and ≤ 2 years, and > 2 years.
• This study included an exercise therapy group comprising land- and water-based therapeutic exercise interventions and a control group comprising no exercise or sham treatment.
• The primary outcomes were self-reported pain and physical function, standardized to a 0-100 scale, at short-term (closest to 3 months) and long-term (closest to 12 months) follow-ups.

TAKEAWAY:

• The overall pain and physical function associated with osteoarthritis improved in the exercise therapy group at both short- and long-term follow-ups compared with in the control group.
• Exercise therapy led to a greater improvement in short-term (mean difference [MD], −3.57; P = .028) and long-term (MD, −8.33; P < .001) pain among participants with a symptom duration ≤ 1 year vs > 1 year.
• Similarly, those with a symptom duration ≤ 2 years vs > 2 years who underwent exercise therapy showed greater benefits in terms of short-term (P = .001) and long-term (P < .001) pain.
• Exercise therapy improved long-term physical function in those with a symptom duration ≤ 1 year vs > 1 year (MD, −5.46; P = .005) and ≤ 2 years vs > 2 years (MD, −4.56; P = .001).

IN PRACTICE:

“Exercise should be encouraged as early as possible once symptoms emerge in the disease process to take advantage of its effects in potentially [slowing] disease progression within the suggested ‘window of opportunity,’ ” the authors wrote.

SOURCE:

The study was led by Marienke van Middelkoop, PhD, Erasmus MC Medical University, Rotterdam, the Netherlands. It was published online in Osteoarthritis and Cartilage.

LIMITATIONS:

The dataset of most studies included in the meta-analysis lacked information on the radiographic severity of osteoarthritis. The relatively short follow-up time hindered interpreting the impact of exercise on the long-term progression of osteoarthritis. The reliance on patient recall for recording symptom duration may have led to misclassification.

DISCLOSURES:

The Netherlands Organisation for Health Research and Development supported this study. Three authors received funding from the Dutch Arthritis Society for the program grant Center of Excellence “OA prevention and early treatment – OA Pearl.” One author declared receiving royalties for the UpToDate knee osteoarthritis clinical guidelines.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

People with knee osteoarthritis and symptoms for less than 1 year benefit more from exercise therapy than do those with longer symptom duration, especially when long-term outcomes are considered.

METHODOLOGY:

• Researchers conducted an individual participant data meta-analysis using data from the OA Trial Bank, including 1769 participants (mean age, 65.1 years; 66% women) with knee osteoarthritis from 10 randomized controlled trials.
• The participants were categorized on the basis of their symptom duration: ≤ 1 year, > 1 and ≤ 2 years, and > 2 years.
• This study included an exercise therapy group comprising land- and water-based therapeutic exercise interventions and a control group comprising no exercise or sham treatment.
• The primary outcomes were self-reported pain and physical function, standardized to a 0-100 scale, at short-term (closest to 3 months) and long-term (closest to 12 months) follow-ups.

TAKEAWAY:

• The overall pain and physical function associated with osteoarthritis improved in the exercise therapy group at both short- and long-term follow-ups compared with in the control group.
• Exercise therapy led to a greater improvement in short-term (mean difference [MD], −3.57; P = .028) and long-term (MD, −8.33; P < .001) pain among participants with a symptom duration ≤ 1 year vs > 1 year.
• Similarly, those with a symptom duration ≤ 2 years vs > 2 years who underwent exercise therapy showed greater benefits in terms of short-term (P = .001) and long-term (P < .001) pain.
• Exercise therapy improved long-term physical function in those with a symptom duration ≤ 1 year vs > 1 year (MD, −5.46; P = .005) and ≤ 2 years vs > 2 years (MD, −4.56; P = .001).

IN PRACTICE:

“Exercise should be encouraged as early as possible once symptoms emerge in the disease process to take advantage of its effects in potentially [slowing] disease progression within the suggested ‘window of opportunity,’ ” the authors wrote.

SOURCE:

The study was led by Marienke van Middelkoop, PhD, Erasmus MC Medical University, Rotterdam, the Netherlands. It was published online in Osteoarthritis and Cartilage.

LIMITATIONS:

The dataset of most studies included in the meta-analysis lacked information on the radiographic severity of osteoarthritis. The relatively short follow-up time hindered interpreting the impact of exercise on the long-term progression of osteoarthritis. The reliance on patient recall for recording symptom duration may have led to misclassification.

DISCLOSURES:

The Netherlands Organisation for Health Research and Development supported this study. Three authors received funding from the Dutch Arthritis Society for the program grant Center of Excellence “OA prevention and early treatment – OA Pearl.” One author declared receiving royalties for the UpToDate knee osteoarthritis clinical guidelines.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

WASHINGTON — Advancing treatment for what has been variably called chronic Lyme and posttreatment Lyme disease (PTLD) is under the eyes of a National Academies of Science, Engineering, and Medicine (NASEM) committee of experts for the first time — a year after the NASEM shone a spotlight on the need to accelerate research on chronic illnesses that follow known or suspected infections.

The committee will not make recommendations on specific approaches to diagnosis and treatment when it issues a report in early 2025 but will instead present “consensus findings” on treatment for chronic illness associated with Lyme disease, including recommendations for advancing treatment.

There have been only a few randomized controlled trials (RCTs) conducted on what the committee is calling Lyme Infection-Associated Chronic Illness (Lyme IACI) for now, and no National Institutes of Health (NIH)-funded RCTs in the past 20 years or so. It’s an area void of the US Food and Drug Administration–approved therapies, void of any consensus on the off-label use of medications, and without any current standard of care or proven mechanisms and pathophysiology, said John Aucott, MD, director of the Johns Hopkins Medicine Lyme Disease Clinical Research Center, Baltimore, one of the invited speakers at a public meeting held by the NASEM in Washington, DC.

“The best way to look at this illness is not from the silos of infectious disease or the silos of rheumatology; you have to look across disciplines,” Dr. Aucott, also associate professor of medicine in the Division of Rheumatology, told the committee. “The story doesn’t fit anything I trained for in my infectious disease fellowship. Even today, I’d posit that PTLD is like an island — it’s still not connected to a lot of the mainstream of medicine.”

Rhisa Parera, who wrote and directed a 2021 documentary, Your Labs Are Normal, was one of several invited speakers who amplified the patient voice. Starting around age 7, she had pain in her knees, spine, and hips and vivid nightmares. In high school, she developed gastrointestinal issues, and in college, she developed debilitating neurologic symptoms.

Depression was her eventual diagnosis after having seen “every specialist in the book,” she said. At age 29, she received a positive western blot test and a Lyme disease diagnosis, at which point “I was prescribed 4 weeks of doxycycline and left in the dark,” the 34-year-old Black patient told the committee. Her health improved only after she began working with an “LLMD,” or Lyme-literate medical doctor (a term used in the patient community), while she lived with her mother and did not work, she said.

“I don’t share my Lyme disease history with other doctors. It’s pointless when you have those who will laugh at you, say you’re fine if you were treated, or just deny the disease completely,” Ms. Parera said. “We need this to be taught in medical school. It’s a literal emergency.”
 

Incidence and Potential Mechanisms

Limited research has suggested that 10%-20% of patients with Lyme disease develop persistent symptoms after standard antibiotic treatment advised by the Infectious Diseases Society of America (IDSA), Dr. Aucott said. (On its web page on chronic symptoms, the Centers for Disease Control and Prevention presents a more conservative range of 5%-10%.)

His own prospective cohort study at Johns Hopkins, published in 2022, found that 13.7% of 234 patients with prior Lyme disease met symptom and functional impact criteria for PTLD, compared with 4.1% of 49 participants without a history of Lyme disease — a statistically significant difference that he said should “put to rest” the question of “is it real?”

PTLD is the research case definition proposed by the IDSA in 2006; it requires that patients have prior documented Lyme disease, no other specific comorbidities, and specific symptoms (fatigue, widespread musculoskeletal pain, and/or cognitive difficulties) causing significant functional impact at least 6 months from their initial diagnosis and treatment.

In the real world, however, where diagnostics for acute Lyme disease are often inaccurate, erythema migrans is often absent, and the symptomatology of Lyme IACI is variable (and where there is no approved laboratory test or objective biomarker for diagnosing Lyme IACI), PTLD represents only a subset of a broader, heterogeneous population with persistent symptoms.

The term “Lyme IACI,” pronounced “Lyme eye-ACK-ee” at the meeting, builds on conversations at the 2023 NASEM workshop on infection-associated chronic illnesses and “encompasses a variety of terms that are used,” including PTLD, PTLD syndrome, persistent Lyme disease, and chronic Lyme disease, according to committee documents. Symptoms are distinct from the known complications of Lyme disease, such as arthritis or carditis.

The findings from Dr. Aucott’s SLICE cohort likely represent “the best outcome,” he said. They’re “probably not generalizable to a community setting where we see lots of missed diagnoses and delayed diagnoses,” as well as other tick-borne coinfections.

One of the challenges in designing future trials, in fact, relates to enrollment criteria and whether to use strict inclusion and exclusion criteria associated with the IDSA definition or take a broader approach to trial enrollment, he and others said. “You want to enroll patients for whom there’s no controversy that they’ve had Lyme infection ... for a study people believe in,” Dr. Aucott said during a discussion period, noting that it’s typical to screen over 100 patients to find one enrollee. “But it’s a tension we’re having.”

Timothy Sellati, PhD, chief scientific officer of the Global Lyme Alliance, urged change. “It’s really important to try to figure out how to alter our thinking on identifying and diagnosing chronic Lyme patients because they need to be recruited into clinical trials,” he said during his presentation.

“We think the best way to do this is to [develop and] employ composite diagnostic testing” that looks at unique Borrelia signatures (eg, protein, DNA, RNA, or metabolites), genetic and/or epigenetic signatures, inflammation signatures, T-cell-independent antibody signatures, and other elements, Dr. Sellati said.

Researchers designing treatment trials also face unknowns, Dr. Aucott and others said, about the role of potential mechanisms of Lyme IACI, from persistent Borrelia burgdorferi (or Borrelia mayonii) infection or the persistence of bacterial remnants (eg, nucleic acids or peptidoglycans) to infection-triggered pathology such as persistent immune dysregulation, chronic inflammation, autoimmunity, microbiome alterations, and dysautonomia and other neural network alterations.

The NASEM’s spotlight on Lyme IACI follows its long COVID-driven push last year to advance a common research agenda in infection-associated chronic illnesses. Investigators see common symptoms and potential shared mechanisms between long COVID, Lyme IACI, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other complex chronic illnesses following infections.

At the Lyme IACI meeting, invited speakers described parts of the research landscape. Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke, for instance, described a recently published deep phenotyping study of 17 patients with ME/CFS that found decreased central catecholamine synthesis, circuit dysfunction of integrative brain regions, and immune profiling differences (eg, defects in B-cell maturation or T-cell exhaustion), compared with matched controls, that suggest the persistence of microbial antigens.

And John Leong, MD, PhD, of Tufts University, Boston, described his lab’s focus on understanding the microbe-host interactions that enable bloodstream dissemination and tissue invasion of B burgdorferi to take hold, increasing the risk for persistent symptoms. Other research at Tufts, he noted during a discussion period, has demonstrated the persistence of B burgdorferi to antibiotics in microtiter dishes. “Those organisms that survive are really difficult to eradicate in vitro,” Dr. Leong said.

Other physician investigators described research on nociplastic pain — a category of pain that can be triggered by infections, causing both amplified sensory processing and augmented central nervous system pain — and on whether reactivation of the Epstein-Barr virus could potentiate autoimmunity in the context of Borrelia infection.

Researchers are ready to test therapies while pathophysiology is unraveled — provided there is funding, Dr. Aucott said. The Clinical Trials Network for Lyme and Other Tick-Borne Diseases, coordinated by Brian Fallon, MD, of Columbia University, New York City, and funded several years ago by the Steven & Alexandra Cohen Foundation, has a slate of small pilot studies underway or being planned that address potential mechanisms (eg, studies of pulse intravenous ceftriaxone, tetracycline, transauricular vagus nerve stimulation, and mast cell modulation). And should full multisite trials be designed and funded, the network is ready with an infrastructure.
 

Need for Patient-Centered Outcomes

Persistent symptomatology is on the NIH’s radar screen. Efforts to understand causes were part of a strategic tick-borne disease research plan developed by the NIH in 2019. And in 2023, the National Institute of Allergy and Infectious Diseases (NIAID) funded seven projects addressing persistent symptoms that will run through 2028, C. Benjamin Beard, PhD, deputy division director of the CDC’s Division of Vector-Borne Disease, said at the NASEM committee meeting.

Patient advocates maintained that too much emphasis is placed on tick biology and pathophysiology. When Wendy Adams, research grant director and advisory board member of the Bay Area Lyme Foundation, and a colleague analyzed NIAID tick-borne disease funding from 2013 to 2021, they found that 75% of the funding went toward basic research, 15% to translational research, and “only 3% went to clinical research,” Ms. Adams told the committee.

Only 3% of the basic research budget was spent on coinfections, she said, and only 1% was spent on neurologic disease associated with tick-borne infections, both of which are survey-defined patient priorities. Moreover, “12% of the overall NIAID [tick-borne diseases] budget was spent on tick biology,” she said.

Research needs to involve community physicians who are utilizing the guidelines and approaches of the International Lyme and Associated Diseases Society to treat most patients with Lyme IACI, Ms. Adams said. “They have data to be mined,” she said, as does LymeDisease.org, which maintains a patient registry, MyLymeData, with over 18,000 patients. The organization has published two treatment studies, including one on antibiotic treatment response.

Lorraine Johnson, JD, MBA, CEO of LymeDisease.org and principal investigator of MyLymeData, stressed the importance of using patient-centered outcomes that incorporate minimal clinically important differences (MCIDs). “A change in the SF-36 score [without consideration of MCIDs] is not inherently important or meaningful to patients,” she said, referring to the SF-36 survey of health-related quality of life.

“This may seem like an esoteric issue, but two of the four clinical trials done [on retreatment of] persistent Lyme disease used the SF-36 as their outcome measure, and those studies, led by [Mark] Klempner, concluded that retreatment was not effective,” Ms. Johnson said. “Patients have been and continue to be harmed by [this research] because they’re told by physicians that antibiotics don’t work.”

A 2012 biostatistical review of these four RCTs — trials that helped inform the 2006 IDSA treatment guidelines — concluded that the Klempner studies “set the bar for treatment success too high,” Ms. Johnson said. Three of the four trials were likely underpowered to detect clinically meaningful treatment effects, the review also found.

The NASEM committee will hold additional public meetings and review a wide range of literature through this year. The formation of the committee was recommended by the US Department of Health and Human Services Tick-Borne Disease Working Group that was established by Congress in 2016 and concluded its work in 2022. The committee’s work is funded by the Cohen Foundation.
 

A version of this article appeared on Medscape.com.

WASHINGTON — Advancing treatment for what has been variably called chronic Lyme and posttreatment Lyme disease (PTLD) is under the eyes of a National Academies of Science, Engineering, and Medicine (NASEM) committee of experts for the first time — a year after the NASEM shone a spotlight on the need to accelerate research on chronic illnesses that follow known or suspected infections.

The committee will not make recommendations on specific approaches to diagnosis and treatment when it issues a report in early 2025 but will instead present “consensus findings” on treatment for chronic illness associated with Lyme disease, including recommendations for advancing treatment.

There have been only a few randomized controlled trials (RCTs) conducted on what the committee is calling Lyme Infection-Associated Chronic Illness (Lyme IACI) for now, and no National Institutes of Health (NIH)-funded RCTs in the past 20 years or so. It’s an area void of the US Food and Drug Administration–approved therapies, void of any consensus on the off-label use of medications, and without any current standard of care or proven mechanisms and pathophysiology, said John Aucott, MD, director of the Johns Hopkins Medicine Lyme Disease Clinical Research Center, Baltimore, one of the invited speakers at a public meeting held by the NASEM in Washington, DC.

“The best way to look at this illness is not from the silos of infectious disease or the silos of rheumatology; you have to look across disciplines,” Dr. Aucott, also associate professor of medicine in the Division of Rheumatology, told the committee. “The story doesn’t fit anything I trained for in my infectious disease fellowship. Even today, I’d posit that PTLD is like an island — it’s still not connected to a lot of the mainstream of medicine.”

Rhisa Parera, who wrote and directed a 2021 documentary, Your Labs Are Normal, was one of several invited speakers who amplified the patient voice. Starting around age 7, she had pain in her knees, spine, and hips and vivid nightmares. In high school, she developed gastrointestinal issues, and in college, she developed debilitating neurologic symptoms.

Depression was her eventual diagnosis after having seen “every specialist in the book,” she said. At age 29, she received a positive western blot test and a Lyme disease diagnosis, at which point “I was prescribed 4 weeks of doxycycline and left in the dark,” the 34-year-old Black patient told the committee. Her health improved only after she began working with an “LLMD,” or Lyme-literate medical doctor (a term used in the patient community), while she lived with her mother and did not work, she said.

“I don’t share my Lyme disease history with other doctors. It’s pointless when you have those who will laugh at you, say you’re fine if you were treated, or just deny the disease completely,” Ms. Parera said. “We need this to be taught in medical school. It’s a literal emergency.”
 

Incidence and Potential Mechanisms

Limited research has suggested that 10%-20% of patients with Lyme disease develop persistent symptoms after standard antibiotic treatment advised by the Infectious Diseases Society of America (IDSA), Dr. Aucott said. (On its web page on chronic symptoms, the Centers for Disease Control and Prevention presents a more conservative range of 5%-10%.)

His own prospective cohort study at Johns Hopkins, published in 2022, found that 13.7% of 234 patients with prior Lyme disease met symptom and functional impact criteria for PTLD, compared with 4.1% of 49 participants without a history of Lyme disease — a statistically significant difference that he said should “put to rest” the question of “is it real?”

PTLD is the research case definition proposed by the IDSA in 2006; it requires that patients have prior documented Lyme disease, no other specific comorbidities, and specific symptoms (fatigue, widespread musculoskeletal pain, and/or cognitive difficulties) causing significant functional impact at least 6 months from their initial diagnosis and treatment.

In the real world, however, where diagnostics for acute Lyme disease are often inaccurate, erythema migrans is often absent, and the symptomatology of Lyme IACI is variable (and where there is no approved laboratory test or objective biomarker for diagnosing Lyme IACI), PTLD represents only a subset of a broader, heterogeneous population with persistent symptoms.

The term “Lyme IACI,” pronounced “Lyme eye-ACK-ee” at the meeting, builds on conversations at the 2023 NASEM workshop on infection-associated chronic illnesses and “encompasses a variety of terms that are used,” including PTLD, PTLD syndrome, persistent Lyme disease, and chronic Lyme disease, according to committee documents. Symptoms are distinct from the known complications of Lyme disease, such as arthritis or carditis.

The findings from Dr. Aucott’s SLICE cohort likely represent “the best outcome,” he said. They’re “probably not generalizable to a community setting where we see lots of missed diagnoses and delayed diagnoses,” as well as other tick-borne coinfections.

One of the challenges in designing future trials, in fact, relates to enrollment criteria and whether to use strict inclusion and exclusion criteria associated with the IDSA definition or take a broader approach to trial enrollment, he and others said. “You want to enroll patients for whom there’s no controversy that they’ve had Lyme infection ... for a study people believe in,” Dr. Aucott said during a discussion period, noting that it’s typical to screen over 100 patients to find one enrollee. “But it’s a tension we’re having.”

Timothy Sellati, PhD, chief scientific officer of the Global Lyme Alliance, urged change. “It’s really important to try to figure out how to alter our thinking on identifying and diagnosing chronic Lyme patients because they need to be recruited into clinical trials,” he said during his presentation.

“We think the best way to do this is to [develop and] employ composite diagnostic testing” that looks at unique Borrelia signatures (eg, protein, DNA, RNA, or metabolites), genetic and/or epigenetic signatures, inflammation signatures, T-cell-independent antibody signatures, and other elements, Dr. Sellati said.

Researchers designing treatment trials also face unknowns, Dr. Aucott and others said, about the role of potential mechanisms of Lyme IACI, from persistent Borrelia burgdorferi (or Borrelia mayonii) infection or the persistence of bacterial remnants (eg, nucleic acids or peptidoglycans) to infection-triggered pathology such as persistent immune dysregulation, chronic inflammation, autoimmunity, microbiome alterations, and dysautonomia and other neural network alterations.

The NASEM’s spotlight on Lyme IACI follows its long COVID-driven push last year to advance a common research agenda in infection-associated chronic illnesses. Investigators see common symptoms and potential shared mechanisms between long COVID, Lyme IACI, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other complex chronic illnesses following infections.

At the Lyme IACI meeting, invited speakers described parts of the research landscape. Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke, for instance, described a recently published deep phenotyping study of 17 patients with ME/CFS that found decreased central catecholamine synthesis, circuit dysfunction of integrative brain regions, and immune profiling differences (eg, defects in B-cell maturation or T-cell exhaustion), compared with matched controls, that suggest the persistence of microbial antigens.

And John Leong, MD, PhD, of Tufts University, Boston, described his lab’s focus on understanding the microbe-host interactions that enable bloodstream dissemination and tissue invasion of B burgdorferi to take hold, increasing the risk for persistent symptoms. Other research at Tufts, he noted during a discussion period, has demonstrated the persistence of B burgdorferi to antibiotics in microtiter dishes. “Those organisms that survive are really difficult to eradicate in vitro,” Dr. Leong said.

Other physician investigators described research on nociplastic pain — a category of pain that can be triggered by infections, causing both amplified sensory processing and augmented central nervous system pain — and on whether reactivation of the Epstein-Barr virus could potentiate autoimmunity in the context of Borrelia infection.

Researchers are ready to test therapies while pathophysiology is unraveled — provided there is funding, Dr. Aucott said. The Clinical Trials Network for Lyme and Other Tick-Borne Diseases, coordinated by Brian Fallon, MD, of Columbia University, New York City, and funded several years ago by the Steven & Alexandra Cohen Foundation, has a slate of small pilot studies underway or being planned that address potential mechanisms (eg, studies of pulse intravenous ceftriaxone, tetracycline, transauricular vagus nerve stimulation, and mast cell modulation). And should full multisite trials be designed and funded, the network is ready with an infrastructure.
 

Need for Patient-Centered Outcomes

Persistent symptomatology is on the NIH’s radar screen. Efforts to understand causes were part of a strategic tick-borne disease research plan developed by the NIH in 2019. And in 2023, the National Institute of Allergy and Infectious Diseases (NIAID) funded seven projects addressing persistent symptoms that will run through 2028, C. Benjamin Beard, PhD, deputy division director of the CDC’s Division of Vector-Borne Disease, said at the NASEM committee meeting.

Patient advocates maintained that too much emphasis is placed on tick biology and pathophysiology. When Wendy Adams, research grant director and advisory board member of the Bay Area Lyme Foundation, and a colleague analyzed NIAID tick-borne disease funding from 2013 to 2021, they found that 75% of the funding went toward basic research, 15% to translational research, and “only 3% went to clinical research,” Ms. Adams told the committee.

Only 3% of the basic research budget was spent on coinfections, she said, and only 1% was spent on neurologic disease associated with tick-borne infections, both of which are survey-defined patient priorities. Moreover, “12% of the overall NIAID [tick-borne diseases] budget was spent on tick biology,” she said.

Research needs to involve community physicians who are utilizing the guidelines and approaches of the International Lyme and Associated Diseases Society to treat most patients with Lyme IACI, Ms. Adams said. “They have data to be mined,” she said, as does LymeDisease.org, which maintains a patient registry, MyLymeData, with over 18,000 patients. The organization has published two treatment studies, including one on antibiotic treatment response.

Lorraine Johnson, JD, MBA, CEO of LymeDisease.org and principal investigator of MyLymeData, stressed the importance of using patient-centered outcomes that incorporate minimal clinically important differences (MCIDs). “A change in the SF-36 score [without consideration of MCIDs] is not inherently important or meaningful to patients,” she said, referring to the SF-36 survey of health-related quality of life.

“This may seem like an esoteric issue, but two of the four clinical trials done [on retreatment of] persistent Lyme disease used the SF-36 as their outcome measure, and those studies, led by [Mark] Klempner, concluded that retreatment was not effective,” Ms. Johnson said. “Patients have been and continue to be harmed by [this research] because they’re told by physicians that antibiotics don’t work.”

A 2012 biostatistical review of these four RCTs — trials that helped inform the 2006 IDSA treatment guidelines — concluded that the Klempner studies “set the bar for treatment success too high,” Ms. Johnson said. Three of the four trials were likely underpowered to detect clinically meaningful treatment effects, the review also found.

The NASEM committee will hold additional public meetings and review a wide range of literature through this year. The formation of the committee was recommended by the US Department of Health and Human Services Tick-Borne Disease Working Group that was established by Congress in 2016 and concluded its work in 2022. The committee’s work is funded by the Cohen Foundation.
 

A version of this article appeared on Medscape.com.

WASHINGTON — Advancing treatment for what has been variably called chronic Lyme and posttreatment Lyme disease (PTLD) is under the eyes of a National Academies of Science, Engineering, and Medicine (NASEM) committee of experts for the first time — a year after the NASEM shone a spotlight on the need to accelerate research on chronic illnesses that follow known or suspected infections.

The committee will not make recommendations on specific approaches to diagnosis and treatment when it issues a report in early 2025 but will instead present “consensus findings” on treatment for chronic illness associated with Lyme disease, including recommendations for advancing treatment.

There have been only a few randomized controlled trials (RCTs) conducted on what the committee is calling Lyme Infection-Associated Chronic Illness (Lyme IACI) for now, and no National Institutes of Health (NIH)-funded RCTs in the past 20 years or so. It’s an area void of the US Food and Drug Administration–approved therapies, void of any consensus on the off-label use of medications, and without any current standard of care or proven mechanisms and pathophysiology, said John Aucott, MD, director of the Johns Hopkins Medicine Lyme Disease Clinical Research Center, Baltimore, one of the invited speakers at a public meeting held by the NASEM in Washington, DC.

“The best way to look at this illness is not from the silos of infectious disease or the silos of rheumatology; you have to look across disciplines,” Dr. Aucott, also associate professor of medicine in the Division of Rheumatology, told the committee. “The story doesn’t fit anything I trained for in my infectious disease fellowship. Even today, I’d posit that PTLD is like an island — it’s still not connected to a lot of the mainstream of medicine.”

Rhisa Parera, who wrote and directed a 2021 documentary, Your Labs Are Normal, was one of several invited speakers who amplified the patient voice. Starting around age 7, she had pain in her knees, spine, and hips and vivid nightmares. In high school, she developed gastrointestinal issues, and in college, she developed debilitating neurologic symptoms.

Depression was her eventual diagnosis after having seen “every specialist in the book,” she said. At age 29, she received a positive western blot test and a Lyme disease diagnosis, at which point “I was prescribed 4 weeks of doxycycline and left in the dark,” the 34-year-old Black patient told the committee. Her health improved only after she began working with an “LLMD,” or Lyme-literate medical doctor (a term used in the patient community), while she lived with her mother and did not work, she said.

“I don’t share my Lyme disease history with other doctors. It’s pointless when you have those who will laugh at you, say you’re fine if you were treated, or just deny the disease completely,” Ms. Parera said. “We need this to be taught in medical school. It’s a literal emergency.”
 

Incidence and Potential Mechanisms

Limited research has suggested that 10%-20% of patients with Lyme disease develop persistent symptoms after standard antibiotic treatment advised by the Infectious Diseases Society of America (IDSA), Dr. Aucott said. (On its web page on chronic symptoms, the Centers for Disease Control and Prevention presents a more conservative range of 5%-10%.)

His own prospective cohort study at Johns Hopkins, published in 2022, found that 13.7% of 234 patients with prior Lyme disease met symptom and functional impact criteria for PTLD, compared with 4.1% of 49 participants without a history of Lyme disease — a statistically significant difference that he said should “put to rest” the question of “is it real?”

PTLD is the research case definition proposed by the IDSA in 2006; it requires that patients have prior documented Lyme disease, no other specific comorbidities, and specific symptoms (fatigue, widespread musculoskeletal pain, and/or cognitive difficulties) causing significant functional impact at least 6 months from their initial diagnosis and treatment.

In the real world, however, where diagnostics for acute Lyme disease are often inaccurate, erythema migrans is often absent, and the symptomatology of Lyme IACI is variable (and where there is no approved laboratory test or objective biomarker for diagnosing Lyme IACI), PTLD represents only a subset of a broader, heterogeneous population with persistent symptoms.

The term “Lyme IACI,” pronounced “Lyme eye-ACK-ee” at the meeting, builds on conversations at the 2023 NASEM workshop on infection-associated chronic illnesses and “encompasses a variety of terms that are used,” including PTLD, PTLD syndrome, persistent Lyme disease, and chronic Lyme disease, according to committee documents. Symptoms are distinct from the known complications of Lyme disease, such as arthritis or carditis.

The findings from Dr. Aucott’s SLICE cohort likely represent “the best outcome,” he said. They’re “probably not generalizable to a community setting where we see lots of missed diagnoses and delayed diagnoses,” as well as other tick-borne coinfections.

One of the challenges in designing future trials, in fact, relates to enrollment criteria and whether to use strict inclusion and exclusion criteria associated with the IDSA definition or take a broader approach to trial enrollment, he and others said. “You want to enroll patients for whom there’s no controversy that they’ve had Lyme infection ... for a study people believe in,” Dr. Aucott said during a discussion period, noting that it’s typical to screen over 100 patients to find one enrollee. “But it’s a tension we’re having.”

Timothy Sellati, PhD, chief scientific officer of the Global Lyme Alliance, urged change. “It’s really important to try to figure out how to alter our thinking on identifying and diagnosing chronic Lyme patients because they need to be recruited into clinical trials,” he said during his presentation.

“We think the best way to do this is to [develop and] employ composite diagnostic testing” that looks at unique Borrelia signatures (eg, protein, DNA, RNA, or metabolites), genetic and/or epigenetic signatures, inflammation signatures, T-cell-independent antibody signatures, and other elements, Dr. Sellati said.

Researchers designing treatment trials also face unknowns, Dr. Aucott and others said, about the role of potential mechanisms of Lyme IACI, from persistent Borrelia burgdorferi (or Borrelia mayonii) infection or the persistence of bacterial remnants (eg, nucleic acids or peptidoglycans) to infection-triggered pathology such as persistent immune dysregulation, chronic inflammation, autoimmunity, microbiome alterations, and dysautonomia and other neural network alterations.

The NASEM’s spotlight on Lyme IACI follows its long COVID-driven push last year to advance a common research agenda in infection-associated chronic illnesses. Investigators see common symptoms and potential shared mechanisms between long COVID, Lyme IACI, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other complex chronic illnesses following infections.

At the Lyme IACI meeting, invited speakers described parts of the research landscape. Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke, for instance, described a recently published deep phenotyping study of 17 patients with ME/CFS that found decreased central catecholamine synthesis, circuit dysfunction of integrative brain regions, and immune profiling differences (eg, defects in B-cell maturation or T-cell exhaustion), compared with matched controls, that suggest the persistence of microbial antigens.

And John Leong, MD, PhD, of Tufts University, Boston, described his lab’s focus on understanding the microbe-host interactions that enable bloodstream dissemination and tissue invasion of B burgdorferi to take hold, increasing the risk for persistent symptoms. Other research at Tufts, he noted during a discussion period, has demonstrated the persistence of B burgdorferi to antibiotics in microtiter dishes. “Those organisms that survive are really difficult to eradicate in vitro,” Dr. Leong said.

Other physician investigators described research on nociplastic pain — a category of pain that can be triggered by infections, causing both amplified sensory processing and augmented central nervous system pain — and on whether reactivation of the Epstein-Barr virus could potentiate autoimmunity in the context of Borrelia infection.

Researchers are ready to test therapies while pathophysiology is unraveled — provided there is funding, Dr. Aucott said. The Clinical Trials Network for Lyme and Other Tick-Borne Diseases, coordinated by Brian Fallon, MD, of Columbia University, New York City, and funded several years ago by the Steven & Alexandra Cohen Foundation, has a slate of small pilot studies underway or being planned that address potential mechanisms (eg, studies of pulse intravenous ceftriaxone, tetracycline, transauricular vagus nerve stimulation, and mast cell modulation). And should full multisite trials be designed and funded, the network is ready with an infrastructure.
 

Need for Patient-Centered Outcomes

Persistent symptomatology is on the NIH’s radar screen. Efforts to understand causes were part of a strategic tick-borne disease research plan developed by the NIH in 2019. And in 2023, the National Institute of Allergy and Infectious Diseases (NIAID) funded seven projects addressing persistent symptoms that will run through 2028, C. Benjamin Beard, PhD, deputy division director of the CDC’s Division of Vector-Borne Disease, said at the NASEM committee meeting.

Patient advocates maintained that too much emphasis is placed on tick biology and pathophysiology. When Wendy Adams, research grant director and advisory board member of the Bay Area Lyme Foundation, and a colleague analyzed NIAID tick-borne disease funding from 2013 to 2021, they found that 75% of the funding went toward basic research, 15% to translational research, and “only 3% went to clinical research,” Ms. Adams told the committee.

Only 3% of the basic research budget was spent on coinfections, she said, and only 1% was spent on neurologic disease associated with tick-borne infections, both of which are survey-defined patient priorities. Moreover, “12% of the overall NIAID [tick-borne diseases] budget was spent on tick biology,” she said.

Research needs to involve community physicians who are utilizing the guidelines and approaches of the International Lyme and Associated Diseases Society to treat most patients with Lyme IACI, Ms. Adams said. “They have data to be mined,” she said, as does LymeDisease.org, which maintains a patient registry, MyLymeData, with over 18,000 patients. The organization has published two treatment studies, including one on antibiotic treatment response.

Lorraine Johnson, JD, MBA, CEO of LymeDisease.org and principal investigator of MyLymeData, stressed the importance of using patient-centered outcomes that incorporate minimal clinically important differences (MCIDs). “A change in the SF-36 score [without consideration of MCIDs] is not inherently important or meaningful to patients,” she said, referring to the SF-36 survey of health-related quality of life.

“This may seem like an esoteric issue, but two of the four clinical trials done [on retreatment of] persistent Lyme disease used the SF-36 as their outcome measure, and those studies, led by [Mark] Klempner, concluded that retreatment was not effective,” Ms. Johnson said. “Patients have been and continue to be harmed by [this research] because they’re told by physicians that antibiotics don’t work.”

A 2012 biostatistical review of these four RCTs — trials that helped inform the 2006 IDSA treatment guidelines — concluded that the Klempner studies “set the bar for treatment success too high,” Ms. Johnson said. Three of the four trials were likely underpowered to detect clinically meaningful treatment effects, the review also found.

The NASEM committee will hold additional public meetings and review a wide range of literature through this year. The formation of the committee was recommended by the US Department of Health and Human Services Tick-Borne Disease Working Group that was established by Congress in 2016 and concluded its work in 2022. The committee’s work is funded by the Cohen Foundation.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

• Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
• To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
• They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
• In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
• The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

• At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
• For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
• Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
• In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

• Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
• To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
• They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
• In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
• The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

• At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
• For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
• Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
• In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

• Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
• To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
• They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
• In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
• The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

• At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
• For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
• Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
• In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

VIENNA — The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

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

An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.

Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.

In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.

The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.

The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.

The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).

Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.

The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.

More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
 

Preventive Interventions Need More Real-World Research

“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.

Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.

“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.

They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.

However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.

The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.

An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.

Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.

In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.

The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.

The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.

The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).

Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.

The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.

More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
 

Preventive Interventions Need More Real-World Research

“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.

Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.

“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.

They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.

However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.

The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.

An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.

Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.

In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.

The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.

The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.

The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).

Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.

The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.

More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
 

Preventive Interventions Need More Real-World Research

“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.

Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.

“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.

They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.

However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.

The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.