User login
Think methotrexate for granulomatous mastitis
MAUI, HAWAII – Methotrexate is the most effective therapy for granulomatous mastitis, according to Anna Postolova, MD, a rheumatology fellow at Stanford (Calif.) University.
Granulomatous mastitis is a rare inflammatory disease of the breast of uncertain but possibly autoimmune etiology. The most common treatments – antibiotics, prednisone, and incision and drainage – are often ineffective and have a roughly 50% recurrence rate. That’s why Stanford rheumatologists began using methotrexate more than a decade ago with impressive results, she explained at the 2018 Rheumatology Winter Clinical Symposium.
Dr. Postolova presented a retrospective series of 19 women referred to Stanford for recurrent or refractory granulomatous mastitis. At diagnosis, they averaged 33.5 years of age with a 6-month history of symptoms prior to diagnosis. Of the 19 women, 11 were Hispanic, and only 2 were Caucasian. A total of 17 women were multiparous, with an average of two children, and 3 women were breastfeeding at symptom onset.
The women were placed on methotrexate at 15 mg/week. At 3 months, 17 of the 19 patients showed improvement, but none had disease resolution. At that point the dose was raised to 20 mg/week. After 3 months at the higher dose, 16 of 18 patients were improved and 4 had experienced resolution of their granulomatous mastitis. After 9 months on methotrexate – 6 at the higher dose – the granulomatous mastitis showed continued improvement in 13 of 15 women and resolution in 8. One woman experienced recurrent disease at 9 months of follow-up after her methotrexate was withheld because of liver test abnormalities and lack of birth control; however, she went into remission upon restarting therapy.
By 12 months, 12 of 15 women, or 80%, had experienced disease resolution. Their methotrexate was then slowly tapered over the course of 18-24 months without disease recurrence.
On the other hand, two women who had previously shown improvement were experiencing mild recurrences at the 12-month mark. They were switched to subcutaneous methotrexate. One responded favorably to the change, and the other had not yet returned for follow-up.
Dr. Postolova reported having no financial conflicts of interest regarding her presentation.
MAUI, HAWAII – Methotrexate is the most effective therapy for granulomatous mastitis, according to Anna Postolova, MD, a rheumatology fellow at Stanford (Calif.) University.
Granulomatous mastitis is a rare inflammatory disease of the breast of uncertain but possibly autoimmune etiology. The most common treatments – antibiotics, prednisone, and incision and drainage – are often ineffective and have a roughly 50% recurrence rate. That’s why Stanford rheumatologists began using methotrexate more than a decade ago with impressive results, she explained at the 2018 Rheumatology Winter Clinical Symposium.
Dr. Postolova presented a retrospective series of 19 women referred to Stanford for recurrent or refractory granulomatous mastitis. At diagnosis, they averaged 33.5 years of age with a 6-month history of symptoms prior to diagnosis. Of the 19 women, 11 were Hispanic, and only 2 were Caucasian. A total of 17 women were multiparous, with an average of two children, and 3 women were breastfeeding at symptom onset.
The women were placed on methotrexate at 15 mg/week. At 3 months, 17 of the 19 patients showed improvement, but none had disease resolution. At that point the dose was raised to 20 mg/week. After 3 months at the higher dose, 16 of 18 patients were improved and 4 had experienced resolution of their granulomatous mastitis. After 9 months on methotrexate – 6 at the higher dose – the granulomatous mastitis showed continued improvement in 13 of 15 women and resolution in 8. One woman experienced recurrent disease at 9 months of follow-up after her methotrexate was withheld because of liver test abnormalities and lack of birth control; however, she went into remission upon restarting therapy.
By 12 months, 12 of 15 women, or 80%, had experienced disease resolution. Their methotrexate was then slowly tapered over the course of 18-24 months without disease recurrence.
On the other hand, two women who had previously shown improvement were experiencing mild recurrences at the 12-month mark. They were switched to subcutaneous methotrexate. One responded favorably to the change, and the other had not yet returned for follow-up.
Dr. Postolova reported having no financial conflicts of interest regarding her presentation.
MAUI, HAWAII – Methotrexate is the most effective therapy for granulomatous mastitis, according to Anna Postolova, MD, a rheumatology fellow at Stanford (Calif.) University.
Granulomatous mastitis is a rare inflammatory disease of the breast of uncertain but possibly autoimmune etiology. The most common treatments – antibiotics, prednisone, and incision and drainage – are often ineffective and have a roughly 50% recurrence rate. That’s why Stanford rheumatologists began using methotrexate more than a decade ago with impressive results, she explained at the 2018 Rheumatology Winter Clinical Symposium.
Dr. Postolova presented a retrospective series of 19 women referred to Stanford for recurrent or refractory granulomatous mastitis. At diagnosis, they averaged 33.5 years of age with a 6-month history of symptoms prior to diagnosis. Of the 19 women, 11 were Hispanic, and only 2 were Caucasian. A total of 17 women were multiparous, with an average of two children, and 3 women were breastfeeding at symptom onset.
The women were placed on methotrexate at 15 mg/week. At 3 months, 17 of the 19 patients showed improvement, but none had disease resolution. At that point the dose was raised to 20 mg/week. After 3 months at the higher dose, 16 of 18 patients were improved and 4 had experienced resolution of their granulomatous mastitis. After 9 months on methotrexate – 6 at the higher dose – the granulomatous mastitis showed continued improvement in 13 of 15 women and resolution in 8. One woman experienced recurrent disease at 9 months of follow-up after her methotrexate was withheld because of liver test abnormalities and lack of birth control; however, she went into remission upon restarting therapy.
By 12 months, 12 of 15 women, or 80%, had experienced disease resolution. Their methotrexate was then slowly tapered over the course of 18-24 months without disease recurrence.
On the other hand, two women who had previously shown improvement were experiencing mild recurrences at the 12-month mark. They were switched to subcutaneous methotrexate. One responded favorably to the change, and the other had not yet returned for follow-up.
Dr. Postolova reported having no financial conflicts of interest regarding her presentation.
EXPERT ANALYSIS FROM RWCS 2018
Key clinical point:
Major finding: At 3 months, 17 of 19 patients showed improvement on methotrexate at 15 mg/week, and at 12 months, 12 of 15 had experienced disease resolution on 20 mg/week.
Study details: A single-center retrospective review of 19 patients with granulomatous mastitis.
Disclosures: The presenter reported having no financial conflicts of interest regarding her presentation.
Maternal biologic therapy does not affect infant vaccine responses
MAUI, HAWAII – The infants of inflammatory bowel disease patients on biologic therapy during pregnancy and breastfeeding do not have a diminished response rate to the inactivated vaccines routinely given during the first 6 months of life, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“Those babies are going to have detectable levels of drug on board, but they respond to vaccines just as well as infants born to mothers with IBD who were not on biologic therapy. The rates are the same, albeit lower than in the general population,” according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
Previous reports from the national registry have established that continuation of biologics in IBD patients throughout pregnancy and breastfeeding to maintain disease control poses no increased risks to the fetus in terms of rates of congenital anomalies, spontaneous abortion, intrauterine growth restriction, low birth weight, or longer-term developmental delay, compared with unexposed babies whose mothers have IBD.
Dr. Ananthakrishnan’s analysis focused on response rates to tetanus and Haemophilus influenzae B vaccines in the infants of 179 PIANO patients. Sixty-five percent of the IBD patients were on various biologic agents during pregnancy, 8% were on a thiopurine, 21% were on combination therapy, and 6% weren’t exposed to any IBD medications. Serologic studies showed that there was no difference across the four groups in terms of infant rates of protective titers in response to the vaccines. However, the 69%-84% rates of protective titers in the four groups fell short of the 90%-plus rate expected in the general population.
Live virus vaccines are contraindicated in the first 6 months of life in infants exposed to maternal biologics in utero. The only live virus vaccine given during that time frame in the United States is rotavirus, administered at months 2 and 3. Dr. Mahadevan and others recommend skipping that vaccine in babies exposed in utero to any IBD biologic other than certolizumab pegol (Cimzia), which uniquely doesn’t cross the placenta.
“That being said, infants born to 71 of our PIANO participants on anti-TNF therapy in pregnancy inadvertently got the rotavirus vaccine, and they were all just fine, even with very high drug levels,” the gastroenterologist said.
The live virus varicella and MMR vaccines can safely be given as scheduled at 1 year of age. By that time the biologics are long gone from the child.
Dr. Mahadevan reported receiving research funding from the Crohn’s and Colitis Foundation of America, which sponsors the PIANO registry. She also has financial relationships with several pharmaceutical companies.
MAUI, HAWAII – The infants of inflammatory bowel disease patients on biologic therapy during pregnancy and breastfeeding do not have a diminished response rate to the inactivated vaccines routinely given during the first 6 months of life, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“Those babies are going to have detectable levels of drug on board, but they respond to vaccines just as well as infants born to mothers with IBD who were not on biologic therapy. The rates are the same, albeit lower than in the general population,” according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
Previous reports from the national registry have established that continuation of biologics in IBD patients throughout pregnancy and breastfeeding to maintain disease control poses no increased risks to the fetus in terms of rates of congenital anomalies, spontaneous abortion, intrauterine growth restriction, low birth weight, or longer-term developmental delay, compared with unexposed babies whose mothers have IBD.
Dr. Ananthakrishnan’s analysis focused on response rates to tetanus and Haemophilus influenzae B vaccines in the infants of 179 PIANO patients. Sixty-five percent of the IBD patients were on various biologic agents during pregnancy, 8% were on a thiopurine, 21% were on combination therapy, and 6% weren’t exposed to any IBD medications. Serologic studies showed that there was no difference across the four groups in terms of infant rates of protective titers in response to the vaccines. However, the 69%-84% rates of protective titers in the four groups fell short of the 90%-plus rate expected in the general population.
Live virus vaccines are contraindicated in the first 6 months of life in infants exposed to maternal biologics in utero. The only live virus vaccine given during that time frame in the United States is rotavirus, administered at months 2 and 3. Dr. Mahadevan and others recommend skipping that vaccine in babies exposed in utero to any IBD biologic other than certolizumab pegol (Cimzia), which uniquely doesn’t cross the placenta.
“That being said, infants born to 71 of our PIANO participants on anti-TNF therapy in pregnancy inadvertently got the rotavirus vaccine, and they were all just fine, even with very high drug levels,” the gastroenterologist said.
The live virus varicella and MMR vaccines can safely be given as scheduled at 1 year of age. By that time the biologics are long gone from the child.
Dr. Mahadevan reported receiving research funding from the Crohn’s and Colitis Foundation of America, which sponsors the PIANO registry. She also has financial relationships with several pharmaceutical companies.
MAUI, HAWAII – The infants of inflammatory bowel disease patients on biologic therapy during pregnancy and breastfeeding do not have a diminished response rate to the inactivated vaccines routinely given during the first 6 months of life, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“Those babies are going to have detectable levels of drug on board, but they respond to vaccines just as well as infants born to mothers with IBD who were not on biologic therapy. The rates are the same, albeit lower than in the general population,” according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
Previous reports from the national registry have established that continuation of biologics in IBD patients throughout pregnancy and breastfeeding to maintain disease control poses no increased risks to the fetus in terms of rates of congenital anomalies, spontaneous abortion, intrauterine growth restriction, low birth weight, or longer-term developmental delay, compared with unexposed babies whose mothers have IBD.
Dr. Ananthakrishnan’s analysis focused on response rates to tetanus and Haemophilus influenzae B vaccines in the infants of 179 PIANO patients. Sixty-five percent of the IBD patients were on various biologic agents during pregnancy, 8% were on a thiopurine, 21% were on combination therapy, and 6% weren’t exposed to any IBD medications. Serologic studies showed that there was no difference across the four groups in terms of infant rates of protective titers in response to the vaccines. However, the 69%-84% rates of protective titers in the four groups fell short of the 90%-plus rate expected in the general population.
Live virus vaccines are contraindicated in the first 6 months of life in infants exposed to maternal biologics in utero. The only live virus vaccine given during that time frame in the United States is rotavirus, administered at months 2 and 3. Dr. Mahadevan and others recommend skipping that vaccine in babies exposed in utero to any IBD biologic other than certolizumab pegol (Cimzia), which uniquely doesn’t cross the placenta.
“That being said, infants born to 71 of our PIANO participants on anti-TNF therapy in pregnancy inadvertently got the rotavirus vaccine, and they were all just fine, even with very high drug levels,” the gastroenterologist said.
The live virus varicella and MMR vaccines can safely be given as scheduled at 1 year of age. By that time the biologics are long gone from the child.
Dr. Mahadevan reported receiving research funding from the Crohn’s and Colitis Foundation of America, which sponsors the PIANO registry. She also has financial relationships with several pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2018
2017 was a big year for psoriatic arthritis
MAUI, HAWAII – 2017 was a banner year in the field of psoriatic arthritis, marked by a huge bump in the number of publications on the topic along with the approval of three additional drugs, Arthur Kavanaugh, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“There is a tremendous amount of excitement now in the field of psoriatic arthritis,” observed Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego.
Together with his colleague Eric M. Ruderman, MD, Dr. Kavanaugh highlighted the three new drug approvals for psoriatic arthritis in 2017 – abatacept(Orencia), tofacitinib(Xeljanz), and ixekizumab(Taltz) – and also discussed important recent studies of several drugs already available.
Abatacept
In the pivotal double-blind, phase 3 trial involving 424 psoriatic arthritis patients, roughly 60% with prior exposure to a tumor necrosis factor inhibitor and 60% on concomitant methotrexate, the proportion of patients with at least 20% improvement in the American College of Rheumatology criteria (ACR20) was 39.4% in patients on the selective T-cell costimulation modulator, compared with 22.3% among placebo-treated controls. The benefit on psoriasis lesions was modest, and there was no significant difference between the two study arms in terms of Health Assessment Questionnaire-Disability Index response rates (Ann Rheum Dis. 2017 Sep;76[9]:1550-8).
“I think we could say the effect is modest,” Dr. Kavanaugh said. “The challenge to us still is to identify patients who are going to have a good response, likely the patients with more joint than skin symptoms.”
An attractive feature of the drug is that its safety profile is well known as a result of its extensive track record in treating RA, he added.
Tofacitinib
On the basis of the phase 3 OPAL Beyond (N Engl J Med. 2017 Oct 19;377[16]:1525-36) and OPAL Broaden (N Engl J Med. 2017 Oct 19;377[16]:1537-50) clinical trials, the dose approved by the Food and Drug Administration for psoriatic arthritis was 5 mg b.i.d.. There was a higher ACR20 response rate with 10 mg than 5 mg b.i.d. in OPAL Broaden, but not in OPAL Beyond. And since there was a suggestion of a higher adverse event rate with the 10-mg b.i.d. dosing without unequivocal evidence of superior efficacy, the Food and Drug Administration – which always puts safety first – went with 5 mg b.i.d., Dr. Ruderman explained.
Ixekizumab
In the phase 3, double-blind SPIRIT-P1 trial, featuring 417 biologic-naive psoriatic arthritis patients, the ACR20 response rate at week 24 was 62.1% with the interleukin-17A antagonist at 80 mg given subcutaneously every 2 weeks and 57.9% when dosed every 4 weeks, compared with 57.4% with adalimumab(Humira) at 40 mg every 2 weeks and 30.2% with placebo (Ann Rheum Dis. 2017 Jan;76[1]:79-87). The FDA-approved regimen was a 160-mg loading dose of ixekizumab, followed by 80 mg every 4 weeks.
Dr. Kavanaugh noted that an international team of investigators has identified beta-defensin 2 as an easily measurable biomarker of interleukin-17A–driven skin pathology after evaluating 170 proteins expressed in blood, psoriasis lesions, and nonlesional skin. It was a small study, with eight psoriasis patients and eight healthy controls studied before and after receiving secukinumab(Cosentyx), a monoclonal antibody directed against interleukin-17A (J Allergy Clin Immunol. 2017 Mar;139[3]:923-932.e8). But it’s a study with big potential implications.
“This natural antibiotic compound we make that’s in the skin might be a marker of responsiveness to anti–interleukin-17 therapy. It could help in deciding which patients get which drugs. This needs further study, especially now that we’re using anti–interleukin-17 drugs more now,” the rheumatologist said.
The year 2017 also brought important new studies of several drugs already available for psoriatic arthritis.
Intravenous golimumab (Simponi Aria)
Dr. Kavanaugh was first author of the GO-VIBRANT study, a phase 3, double-blind clinical trial in which 480 biologic-naive psoriatic arthritis patients were randomized to a 30-minute infusion of IV golimumab at 2 mg/kg or placebo at weeks 0, 4, 12, and 20.
The primary endpoint, an ACR20 response at week 14, was achieved in 75.1% of patients on the tumor necrosis factor inhibitor versus 21.8% on placebo. An ACR50 response occurred in 43.6% of patients on IV golimumab, compared with 6.3% on placebo, and a Psoriasis and Area Severity Index 75 skin response was achieved in 59.2% on IV golimumab and 13.6% of controls. At week 24, the IV golimumab group demonstrated significantly less radiographic progression as measured by the total modified Sharp/van der Heijde score. The drug was well tolerated, with no opportunistic infections or tuberculosis, and the infusion reaction rate was below 2% (Arthritis Rheumatol. 2017 Nov;69[11]:2151-61).
Secukinumab
In a recent update of the 606-patient FUTURE 1 trial, secukinumab resulted in clinically meaningful improvement in key patient-reported outcomes at week 24, including global assessment of disease activity, which decreased by a mean of 20.6 and 20 points in patients on 150 and 75 mg, respectively, every 4 weeks, compared with a 7.4-point drop in placebo-treated controls.
Psoriatic arthritis quality of life scores improved by 3.5 and 3.2 points in the two secukinumab arms, compared with 0.4 points in controls. Dermatology Life Quality Index scores improved by 8.8 and 7.9 points, versus 0.7 in controls. Patients on the interleukin-17A inhibitor also showed significantly greater improvement in self-assessments measuring pain and fatigue (Ann Rheum Dis. 2017 Jan;76[1]:203-7).
Apremilast (Otezla)
At the 2018 meeting of the American Academy of Dermatology, Dr. Kavanaugh presented 5-year outcomes of the open-label extension of the 504-patient, phase 3 PALACE-1 trial. In an as-observed analysis, patients on apremilast 30 mg b.i.d. up to week 260 had a 71.7% ACR20 response rate, a 48.6% ACR50 response rate, and a 28.4% ACR70 response. Eighty percent of patients on the oral phosphodiesterase-4 (PDE-4) inhibitor had a dactylitis count of 0, and 54.5% had a Maastricht Ankylosing Spondylitis Enthesitis Score of 0.
In a report from the 219-patient, phase 3B ACTIVE trial, investigators showed that biologic-naive patients randomized to apremilast at 30 mg b.i.d. had a significantly greater ACR20 response as early as week 2, which was the first assessment. At that point, the ACR20 rate was 16.4% with apremilast, compared with 6.4% in placebo-treated controls. The apremilast group also demonstrated significant early improvements in patient-reported outcomes, including the Health Assessment Questionnaire-Disability Index, morning stiffness, and enthesitis severity.
The primary outcome, the ACR20 rate at week 16, was 38.2% with active treatment versus 20.2% in controls (Ann Rheum Dis. 2018 Jan 17. doi: 10.1136/annrheumdis-2017-211568).
“The main advantage of apremilast is safety – and that’s a big advantage,” Dr. Kavanaugh commented.
Military physicians tell him they are prescribing a lot of apremilast for armed forces deploying overseas because it’s not immunosuppressive and doesn’t entail laboratory testing.
The research agenda for PDE-4 inhibition in psoriatic disease is extensive, he noted. There is a need for formal studies of PDE-4 inhibition in combination with conventional disease-modifying antirheumatic drugs or biologics. Topical formulations, once-daily dosing, and the possibility that PDE-4 inhibition might be the preferred therapy in patients with certain comorbid conditions, such as chronic obstructive pulmonary disease or a history of recurrent infections, are all topics worthy of study. A biomarker to identify in advance which patients with psoriatic arthritis or psoriasis will attain maximum clinical benefit from apremilast, and in which domains, would be of enormous help to clinicians.
Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.
MAUI, HAWAII – 2017 was a banner year in the field of psoriatic arthritis, marked by a huge bump in the number of publications on the topic along with the approval of three additional drugs, Arthur Kavanaugh, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“There is a tremendous amount of excitement now in the field of psoriatic arthritis,” observed Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego.
Together with his colleague Eric M. Ruderman, MD, Dr. Kavanaugh highlighted the three new drug approvals for psoriatic arthritis in 2017 – abatacept(Orencia), tofacitinib(Xeljanz), and ixekizumab(Taltz) – and also discussed important recent studies of several drugs already available.
Abatacept
In the pivotal double-blind, phase 3 trial involving 424 psoriatic arthritis patients, roughly 60% with prior exposure to a tumor necrosis factor inhibitor and 60% on concomitant methotrexate, the proportion of patients with at least 20% improvement in the American College of Rheumatology criteria (ACR20) was 39.4% in patients on the selective T-cell costimulation modulator, compared with 22.3% among placebo-treated controls. The benefit on psoriasis lesions was modest, and there was no significant difference between the two study arms in terms of Health Assessment Questionnaire-Disability Index response rates (Ann Rheum Dis. 2017 Sep;76[9]:1550-8).
“I think we could say the effect is modest,” Dr. Kavanaugh said. “The challenge to us still is to identify patients who are going to have a good response, likely the patients with more joint than skin symptoms.”
An attractive feature of the drug is that its safety profile is well known as a result of its extensive track record in treating RA, he added.
Tofacitinib
On the basis of the phase 3 OPAL Beyond (N Engl J Med. 2017 Oct 19;377[16]:1525-36) and OPAL Broaden (N Engl J Med. 2017 Oct 19;377[16]:1537-50) clinical trials, the dose approved by the Food and Drug Administration for psoriatic arthritis was 5 mg b.i.d.. There was a higher ACR20 response rate with 10 mg than 5 mg b.i.d. in OPAL Broaden, but not in OPAL Beyond. And since there was a suggestion of a higher adverse event rate with the 10-mg b.i.d. dosing without unequivocal evidence of superior efficacy, the Food and Drug Administration – which always puts safety first – went with 5 mg b.i.d., Dr. Ruderman explained.
Ixekizumab
In the phase 3, double-blind SPIRIT-P1 trial, featuring 417 biologic-naive psoriatic arthritis patients, the ACR20 response rate at week 24 was 62.1% with the interleukin-17A antagonist at 80 mg given subcutaneously every 2 weeks and 57.9% when dosed every 4 weeks, compared with 57.4% with adalimumab(Humira) at 40 mg every 2 weeks and 30.2% with placebo (Ann Rheum Dis. 2017 Jan;76[1]:79-87). The FDA-approved regimen was a 160-mg loading dose of ixekizumab, followed by 80 mg every 4 weeks.
Dr. Kavanaugh noted that an international team of investigators has identified beta-defensin 2 as an easily measurable biomarker of interleukin-17A–driven skin pathology after evaluating 170 proteins expressed in blood, psoriasis lesions, and nonlesional skin. It was a small study, with eight psoriasis patients and eight healthy controls studied before and after receiving secukinumab(Cosentyx), a monoclonal antibody directed against interleukin-17A (J Allergy Clin Immunol. 2017 Mar;139[3]:923-932.e8). But it’s a study with big potential implications.
“This natural antibiotic compound we make that’s in the skin might be a marker of responsiveness to anti–interleukin-17 therapy. It could help in deciding which patients get which drugs. This needs further study, especially now that we’re using anti–interleukin-17 drugs more now,” the rheumatologist said.
The year 2017 also brought important new studies of several drugs already available for psoriatic arthritis.
Intravenous golimumab (Simponi Aria)
Dr. Kavanaugh was first author of the GO-VIBRANT study, a phase 3, double-blind clinical trial in which 480 biologic-naive psoriatic arthritis patients were randomized to a 30-minute infusion of IV golimumab at 2 mg/kg or placebo at weeks 0, 4, 12, and 20.
The primary endpoint, an ACR20 response at week 14, was achieved in 75.1% of patients on the tumor necrosis factor inhibitor versus 21.8% on placebo. An ACR50 response occurred in 43.6% of patients on IV golimumab, compared with 6.3% on placebo, and a Psoriasis and Area Severity Index 75 skin response was achieved in 59.2% on IV golimumab and 13.6% of controls. At week 24, the IV golimumab group demonstrated significantly less radiographic progression as measured by the total modified Sharp/van der Heijde score. The drug was well tolerated, with no opportunistic infections or tuberculosis, and the infusion reaction rate was below 2% (Arthritis Rheumatol. 2017 Nov;69[11]:2151-61).
Secukinumab
In a recent update of the 606-patient FUTURE 1 trial, secukinumab resulted in clinically meaningful improvement in key patient-reported outcomes at week 24, including global assessment of disease activity, which decreased by a mean of 20.6 and 20 points in patients on 150 and 75 mg, respectively, every 4 weeks, compared with a 7.4-point drop in placebo-treated controls.
Psoriatic arthritis quality of life scores improved by 3.5 and 3.2 points in the two secukinumab arms, compared with 0.4 points in controls. Dermatology Life Quality Index scores improved by 8.8 and 7.9 points, versus 0.7 in controls. Patients on the interleukin-17A inhibitor also showed significantly greater improvement in self-assessments measuring pain and fatigue (Ann Rheum Dis. 2017 Jan;76[1]:203-7).
Apremilast (Otezla)
At the 2018 meeting of the American Academy of Dermatology, Dr. Kavanaugh presented 5-year outcomes of the open-label extension of the 504-patient, phase 3 PALACE-1 trial. In an as-observed analysis, patients on apremilast 30 mg b.i.d. up to week 260 had a 71.7% ACR20 response rate, a 48.6% ACR50 response rate, and a 28.4% ACR70 response. Eighty percent of patients on the oral phosphodiesterase-4 (PDE-4) inhibitor had a dactylitis count of 0, and 54.5% had a Maastricht Ankylosing Spondylitis Enthesitis Score of 0.
In a report from the 219-patient, phase 3B ACTIVE trial, investigators showed that biologic-naive patients randomized to apremilast at 30 mg b.i.d. had a significantly greater ACR20 response as early as week 2, which was the first assessment. At that point, the ACR20 rate was 16.4% with apremilast, compared with 6.4% in placebo-treated controls. The apremilast group also demonstrated significant early improvements in patient-reported outcomes, including the Health Assessment Questionnaire-Disability Index, morning stiffness, and enthesitis severity.
The primary outcome, the ACR20 rate at week 16, was 38.2% with active treatment versus 20.2% in controls (Ann Rheum Dis. 2018 Jan 17. doi: 10.1136/annrheumdis-2017-211568).
“The main advantage of apremilast is safety – and that’s a big advantage,” Dr. Kavanaugh commented.
Military physicians tell him they are prescribing a lot of apremilast for armed forces deploying overseas because it’s not immunosuppressive and doesn’t entail laboratory testing.
The research agenda for PDE-4 inhibition in psoriatic disease is extensive, he noted. There is a need for formal studies of PDE-4 inhibition in combination with conventional disease-modifying antirheumatic drugs or biologics. Topical formulations, once-daily dosing, and the possibility that PDE-4 inhibition might be the preferred therapy in patients with certain comorbid conditions, such as chronic obstructive pulmonary disease or a history of recurrent infections, are all topics worthy of study. A biomarker to identify in advance which patients with psoriatic arthritis or psoriasis will attain maximum clinical benefit from apremilast, and in which domains, would be of enormous help to clinicians.
Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.
MAUI, HAWAII – 2017 was a banner year in the field of psoriatic arthritis, marked by a huge bump in the number of publications on the topic along with the approval of three additional drugs, Arthur Kavanaugh, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“There is a tremendous amount of excitement now in the field of psoriatic arthritis,” observed Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego.
Together with his colleague Eric M. Ruderman, MD, Dr. Kavanaugh highlighted the three new drug approvals for psoriatic arthritis in 2017 – abatacept(Orencia), tofacitinib(Xeljanz), and ixekizumab(Taltz) – and also discussed important recent studies of several drugs already available.
Abatacept
In the pivotal double-blind, phase 3 trial involving 424 psoriatic arthritis patients, roughly 60% with prior exposure to a tumor necrosis factor inhibitor and 60% on concomitant methotrexate, the proportion of patients with at least 20% improvement in the American College of Rheumatology criteria (ACR20) was 39.4% in patients on the selective T-cell costimulation modulator, compared with 22.3% among placebo-treated controls. The benefit on psoriasis lesions was modest, and there was no significant difference between the two study arms in terms of Health Assessment Questionnaire-Disability Index response rates (Ann Rheum Dis. 2017 Sep;76[9]:1550-8).
“I think we could say the effect is modest,” Dr. Kavanaugh said. “The challenge to us still is to identify patients who are going to have a good response, likely the patients with more joint than skin symptoms.”
An attractive feature of the drug is that its safety profile is well known as a result of its extensive track record in treating RA, he added.
Tofacitinib
On the basis of the phase 3 OPAL Beyond (N Engl J Med. 2017 Oct 19;377[16]:1525-36) and OPAL Broaden (N Engl J Med. 2017 Oct 19;377[16]:1537-50) clinical trials, the dose approved by the Food and Drug Administration for psoriatic arthritis was 5 mg b.i.d.. There was a higher ACR20 response rate with 10 mg than 5 mg b.i.d. in OPAL Broaden, but not in OPAL Beyond. And since there was a suggestion of a higher adverse event rate with the 10-mg b.i.d. dosing without unequivocal evidence of superior efficacy, the Food and Drug Administration – which always puts safety first – went with 5 mg b.i.d., Dr. Ruderman explained.
Ixekizumab
In the phase 3, double-blind SPIRIT-P1 trial, featuring 417 biologic-naive psoriatic arthritis patients, the ACR20 response rate at week 24 was 62.1% with the interleukin-17A antagonist at 80 mg given subcutaneously every 2 weeks and 57.9% when dosed every 4 weeks, compared with 57.4% with adalimumab(Humira) at 40 mg every 2 weeks and 30.2% with placebo (Ann Rheum Dis. 2017 Jan;76[1]:79-87). The FDA-approved regimen was a 160-mg loading dose of ixekizumab, followed by 80 mg every 4 weeks.
Dr. Kavanaugh noted that an international team of investigators has identified beta-defensin 2 as an easily measurable biomarker of interleukin-17A–driven skin pathology after evaluating 170 proteins expressed in blood, psoriasis lesions, and nonlesional skin. It was a small study, with eight psoriasis patients and eight healthy controls studied before and after receiving secukinumab(Cosentyx), a monoclonal antibody directed against interleukin-17A (J Allergy Clin Immunol. 2017 Mar;139[3]:923-932.e8). But it’s a study with big potential implications.
“This natural antibiotic compound we make that’s in the skin might be a marker of responsiveness to anti–interleukin-17 therapy. It could help in deciding which patients get which drugs. This needs further study, especially now that we’re using anti–interleukin-17 drugs more now,” the rheumatologist said.
The year 2017 also brought important new studies of several drugs already available for psoriatic arthritis.
Intravenous golimumab (Simponi Aria)
Dr. Kavanaugh was first author of the GO-VIBRANT study, a phase 3, double-blind clinical trial in which 480 biologic-naive psoriatic arthritis patients were randomized to a 30-minute infusion of IV golimumab at 2 mg/kg or placebo at weeks 0, 4, 12, and 20.
The primary endpoint, an ACR20 response at week 14, was achieved in 75.1% of patients on the tumor necrosis factor inhibitor versus 21.8% on placebo. An ACR50 response occurred in 43.6% of patients on IV golimumab, compared with 6.3% on placebo, and a Psoriasis and Area Severity Index 75 skin response was achieved in 59.2% on IV golimumab and 13.6% of controls. At week 24, the IV golimumab group demonstrated significantly less radiographic progression as measured by the total modified Sharp/van der Heijde score. The drug was well tolerated, with no opportunistic infections or tuberculosis, and the infusion reaction rate was below 2% (Arthritis Rheumatol. 2017 Nov;69[11]:2151-61).
Secukinumab
In a recent update of the 606-patient FUTURE 1 trial, secukinumab resulted in clinically meaningful improvement in key patient-reported outcomes at week 24, including global assessment of disease activity, which decreased by a mean of 20.6 and 20 points in patients on 150 and 75 mg, respectively, every 4 weeks, compared with a 7.4-point drop in placebo-treated controls.
Psoriatic arthritis quality of life scores improved by 3.5 and 3.2 points in the two secukinumab arms, compared with 0.4 points in controls. Dermatology Life Quality Index scores improved by 8.8 and 7.9 points, versus 0.7 in controls. Patients on the interleukin-17A inhibitor also showed significantly greater improvement in self-assessments measuring pain and fatigue (Ann Rheum Dis. 2017 Jan;76[1]:203-7).
Apremilast (Otezla)
At the 2018 meeting of the American Academy of Dermatology, Dr. Kavanaugh presented 5-year outcomes of the open-label extension of the 504-patient, phase 3 PALACE-1 trial. In an as-observed analysis, patients on apremilast 30 mg b.i.d. up to week 260 had a 71.7% ACR20 response rate, a 48.6% ACR50 response rate, and a 28.4% ACR70 response. Eighty percent of patients on the oral phosphodiesterase-4 (PDE-4) inhibitor had a dactylitis count of 0, and 54.5% had a Maastricht Ankylosing Spondylitis Enthesitis Score of 0.
In a report from the 219-patient, phase 3B ACTIVE trial, investigators showed that biologic-naive patients randomized to apremilast at 30 mg b.i.d. had a significantly greater ACR20 response as early as week 2, which was the first assessment. At that point, the ACR20 rate was 16.4% with apremilast, compared with 6.4% in placebo-treated controls. The apremilast group also demonstrated significant early improvements in patient-reported outcomes, including the Health Assessment Questionnaire-Disability Index, morning stiffness, and enthesitis severity.
The primary outcome, the ACR20 rate at week 16, was 38.2% with active treatment versus 20.2% in controls (Ann Rheum Dis. 2018 Jan 17. doi: 10.1136/annrheumdis-2017-211568).
“The main advantage of apremilast is safety – and that’s a big advantage,” Dr. Kavanaugh commented.
Military physicians tell him they are prescribing a lot of apremilast for armed forces deploying overseas because it’s not immunosuppressive and doesn’t entail laboratory testing.
The research agenda for PDE-4 inhibition in psoriatic disease is extensive, he noted. There is a need for formal studies of PDE-4 inhibition in combination with conventional disease-modifying antirheumatic drugs or biologics. Topical formulations, once-daily dosing, and the possibility that PDE-4 inhibition might be the preferred therapy in patients with certain comorbid conditions, such as chronic obstructive pulmonary disease or a history of recurrent infections, are all topics worthy of study. A biomarker to identify in advance which patients with psoriatic arthritis or psoriasis will attain maximum clinical benefit from apremilast, and in which domains, would be of enormous help to clinicians.
Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2018
Psoriatic arthritis treatment: “We’re not doing so well”
MAUI, HAWAII – Two recent Scandinavian studies highlight the considerable room for improvement that exists in psoriatic arthritis outcomes, according to speakers at the 2018 Rheumatology Winter Clinical Symposium.
“We’re not doing so well. I think that in general, ,” declared Arthur Kavanaugh, MD, program director for the symposium and professor of medicine at the University of California, San Diego.
“If you say that MDA is remission, a 23% remission rate is not good enough. And there are some people who are not on treatment. So I think we’re still seeing a lag in psoriatic arthritis. We’re not treating it as aggressively as we are rheumatoid arthritis,” said Dr. Kavanaugh, director of the Center for Innovative Therapy in the university’s division of rheumatology, allergy, and immunology.
“This study was a surprise,” he continued. “I think it’s like rheumatoid arthritis was years ago. If you asked docs how they were doing, they would say, ‘My patients are doing great!’ But then you go to the office and measure the patients and it’s like, ‘Well, not so much.’ ”
Another speaker, Eric M. Ruderman, MD, concurred.
That being said, it’s also clear that rheumatologists aren’t doing as well in managing psoriatic arthritis as dermatologists are with psoriasis, where skin clearance or almost-clear rates unimaginable just a few years ago are now routinely attainable, he added.
“In dermatology they’re getting better and better and better and better with each successive new cytokine target. We’re not. The ACR responses with risankizumab [an investigational anti-interleukin-23 p19 inhibitor] are very much like we saw with the tumor necrosis factor inhibitors. The interleukin-12/23 inhibitor responses are very much like we’ve seen with the interleukin-17 inhibitors. So each successive improvement in getting skin disease under control hasn’t really gotten us very much further with joint disease. I don’t know that we’ve cracked that yet,” Dr. Ruderman said.
Another recent Scandinavian psoriatic arthritis study that particularly impressed Dr. Kavanaugh was a Danish nationwide cohort registry study that shed new light upon the burdens imposed by the disease in terms of societal costs, comorbid conditions, and disability. The subjects were 10,525 Danes with psoriatic arthritis and nearly 21,000 matched general population controls evaluated during the period from 5 years prior to diagnosis of psoriatic arthritis through 10 years after.
The costs were impressive: an average of 10,641 euros more per year per psoriatic arthritis patient, compared with controls, during the 10-year period following diagnosis, with most of the difference attributed to higher health care costs and forgone earnings due to unemployment, early retirement, or receipt of a disability pension.
At the time of their diagnosis, psoriatic arthritis patients had a significantly higher burden of comorbid conditions than did controls, including a 1.7-fold higher likelihood of cardiovascular disease, a 1.73-fold increase in risk for pulmonary disease, a 2.03-fold greater likelihood of infectious diseases, and a 1.94-fold increased risk of hematologic disorders.
Five years prior to diagnosis of psoriatic arthritis, affected individuals were 1.36-fold more likely than were controls to be on a disability pension. At diagnosis, they were 1.6-fold more likely. Ten years after diagnosis of psoriatic arthritis, they were 2.69-fold more likely to be on a disability pension. Indeed, by that point, 21.8% of Danish psoriatic arthritis patients were on disability (Ann Rheum Dis. 2017 Sep;76([9]:1495-1501).
Health care costs began rising steeply at least 3 years prior to diagnosis of psoriatic arthritis, as well.
“We need to do better with our psoriatic arthritis patients. I think this beautiful study is a call to attention for us to make sure that we’re identifying people with psoriatic arthritis as early as we can,” Dr. Kavanaugh said.
As for the treat-to-target approach that has become so widespread in the management of rheumatoid arthritis, it has gained a toehold in the treatment of psoriatic arthritis. Dr. Kavanaugh was a member of an international task force that recently published treat-to-target recommendations for psoriatic arthritis and axial spondyloarthritis (Ann Rheum Dis. 2018 Jan;77[1]:3-17).
The recommendation for defining the target in psoriatic arthritis was to use the DAPSA or MDA. However, this was a controversial recommendation because of the dearth of evidence. It passed with 51.6% of the task force votes and a level of agreement of 7.9 on a 0-10 scale.
Despite the demonstrable room for improvement in psoriatic arthritis treatment outcomes, better times are likely to be coming for affected patients. A record-breaking number of publications on psoriatic arthritis was published in 2017, and three additional drugs received marketing approval for the disease.
Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.
MAUI, HAWAII – Two recent Scandinavian studies highlight the considerable room for improvement that exists in psoriatic arthritis outcomes, according to speakers at the 2018 Rheumatology Winter Clinical Symposium.
“We’re not doing so well. I think that in general, ,” declared Arthur Kavanaugh, MD, program director for the symposium and professor of medicine at the University of California, San Diego.
“If you say that MDA is remission, a 23% remission rate is not good enough. And there are some people who are not on treatment. So I think we’re still seeing a lag in psoriatic arthritis. We’re not treating it as aggressively as we are rheumatoid arthritis,” said Dr. Kavanaugh, director of the Center for Innovative Therapy in the university’s division of rheumatology, allergy, and immunology.
“This study was a surprise,” he continued. “I think it’s like rheumatoid arthritis was years ago. If you asked docs how they were doing, they would say, ‘My patients are doing great!’ But then you go to the office and measure the patients and it’s like, ‘Well, not so much.’ ”
Another speaker, Eric M. Ruderman, MD, concurred.
That being said, it’s also clear that rheumatologists aren’t doing as well in managing psoriatic arthritis as dermatologists are with psoriasis, where skin clearance or almost-clear rates unimaginable just a few years ago are now routinely attainable, he added.
“In dermatology they’re getting better and better and better and better with each successive new cytokine target. We’re not. The ACR responses with risankizumab [an investigational anti-interleukin-23 p19 inhibitor] are very much like we saw with the tumor necrosis factor inhibitors. The interleukin-12/23 inhibitor responses are very much like we’ve seen with the interleukin-17 inhibitors. So each successive improvement in getting skin disease under control hasn’t really gotten us very much further with joint disease. I don’t know that we’ve cracked that yet,” Dr. Ruderman said.
Another recent Scandinavian psoriatic arthritis study that particularly impressed Dr. Kavanaugh was a Danish nationwide cohort registry study that shed new light upon the burdens imposed by the disease in terms of societal costs, comorbid conditions, and disability. The subjects were 10,525 Danes with psoriatic arthritis and nearly 21,000 matched general population controls evaluated during the period from 5 years prior to diagnosis of psoriatic arthritis through 10 years after.
The costs were impressive: an average of 10,641 euros more per year per psoriatic arthritis patient, compared with controls, during the 10-year period following diagnosis, with most of the difference attributed to higher health care costs and forgone earnings due to unemployment, early retirement, or receipt of a disability pension.
At the time of their diagnosis, psoriatic arthritis patients had a significantly higher burden of comorbid conditions than did controls, including a 1.7-fold higher likelihood of cardiovascular disease, a 1.73-fold increase in risk for pulmonary disease, a 2.03-fold greater likelihood of infectious diseases, and a 1.94-fold increased risk of hematologic disorders.
Five years prior to diagnosis of psoriatic arthritis, affected individuals were 1.36-fold more likely than were controls to be on a disability pension. At diagnosis, they were 1.6-fold more likely. Ten years after diagnosis of psoriatic arthritis, they were 2.69-fold more likely to be on a disability pension. Indeed, by that point, 21.8% of Danish psoriatic arthritis patients were on disability (Ann Rheum Dis. 2017 Sep;76([9]:1495-1501).
Health care costs began rising steeply at least 3 years prior to diagnosis of psoriatic arthritis, as well.
“We need to do better with our psoriatic arthritis patients. I think this beautiful study is a call to attention for us to make sure that we’re identifying people with psoriatic arthritis as early as we can,” Dr. Kavanaugh said.
As for the treat-to-target approach that has become so widespread in the management of rheumatoid arthritis, it has gained a toehold in the treatment of psoriatic arthritis. Dr. Kavanaugh was a member of an international task force that recently published treat-to-target recommendations for psoriatic arthritis and axial spondyloarthritis (Ann Rheum Dis. 2018 Jan;77[1]:3-17).
The recommendation for defining the target in psoriatic arthritis was to use the DAPSA or MDA. However, this was a controversial recommendation because of the dearth of evidence. It passed with 51.6% of the task force votes and a level of agreement of 7.9 on a 0-10 scale.
Despite the demonstrable room for improvement in psoriatic arthritis treatment outcomes, better times are likely to be coming for affected patients. A record-breaking number of publications on psoriatic arthritis was published in 2017, and three additional drugs received marketing approval for the disease.
Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.
MAUI, HAWAII – Two recent Scandinavian studies highlight the considerable room for improvement that exists in psoriatic arthritis outcomes, according to speakers at the 2018 Rheumatology Winter Clinical Symposium.
“We’re not doing so well. I think that in general, ,” declared Arthur Kavanaugh, MD, program director for the symposium and professor of medicine at the University of California, San Diego.
“If you say that MDA is remission, a 23% remission rate is not good enough. And there are some people who are not on treatment. So I think we’re still seeing a lag in psoriatic arthritis. We’re not treating it as aggressively as we are rheumatoid arthritis,” said Dr. Kavanaugh, director of the Center for Innovative Therapy in the university’s division of rheumatology, allergy, and immunology.
“This study was a surprise,” he continued. “I think it’s like rheumatoid arthritis was years ago. If you asked docs how they were doing, they would say, ‘My patients are doing great!’ But then you go to the office and measure the patients and it’s like, ‘Well, not so much.’ ”
Another speaker, Eric M. Ruderman, MD, concurred.
That being said, it’s also clear that rheumatologists aren’t doing as well in managing psoriatic arthritis as dermatologists are with psoriasis, where skin clearance or almost-clear rates unimaginable just a few years ago are now routinely attainable, he added.
“In dermatology they’re getting better and better and better and better with each successive new cytokine target. We’re not. The ACR responses with risankizumab [an investigational anti-interleukin-23 p19 inhibitor] are very much like we saw with the tumor necrosis factor inhibitors. The interleukin-12/23 inhibitor responses are very much like we’ve seen with the interleukin-17 inhibitors. So each successive improvement in getting skin disease under control hasn’t really gotten us very much further with joint disease. I don’t know that we’ve cracked that yet,” Dr. Ruderman said.
Another recent Scandinavian psoriatic arthritis study that particularly impressed Dr. Kavanaugh was a Danish nationwide cohort registry study that shed new light upon the burdens imposed by the disease in terms of societal costs, comorbid conditions, and disability. The subjects were 10,525 Danes with psoriatic arthritis and nearly 21,000 matched general population controls evaluated during the period from 5 years prior to diagnosis of psoriatic arthritis through 10 years after.
The costs were impressive: an average of 10,641 euros more per year per psoriatic arthritis patient, compared with controls, during the 10-year period following diagnosis, with most of the difference attributed to higher health care costs and forgone earnings due to unemployment, early retirement, or receipt of a disability pension.
At the time of their diagnosis, psoriatic arthritis patients had a significantly higher burden of comorbid conditions than did controls, including a 1.7-fold higher likelihood of cardiovascular disease, a 1.73-fold increase in risk for pulmonary disease, a 2.03-fold greater likelihood of infectious diseases, and a 1.94-fold increased risk of hematologic disorders.
Five years prior to diagnosis of psoriatic arthritis, affected individuals were 1.36-fold more likely than were controls to be on a disability pension. At diagnosis, they were 1.6-fold more likely. Ten years after diagnosis of psoriatic arthritis, they were 2.69-fold more likely to be on a disability pension. Indeed, by that point, 21.8% of Danish psoriatic arthritis patients were on disability (Ann Rheum Dis. 2017 Sep;76([9]:1495-1501).
Health care costs began rising steeply at least 3 years prior to diagnosis of psoriatic arthritis, as well.
“We need to do better with our psoriatic arthritis patients. I think this beautiful study is a call to attention for us to make sure that we’re identifying people with psoriatic arthritis as early as we can,” Dr. Kavanaugh said.
As for the treat-to-target approach that has become so widespread in the management of rheumatoid arthritis, it has gained a toehold in the treatment of psoriatic arthritis. Dr. Kavanaugh was a member of an international task force that recently published treat-to-target recommendations for psoriatic arthritis and axial spondyloarthritis (Ann Rheum Dis. 2018 Jan;77[1]:3-17).
The recommendation for defining the target in psoriatic arthritis was to use the DAPSA or MDA. However, this was a controversial recommendation because of the dearth of evidence. It passed with 51.6% of the task force votes and a level of agreement of 7.9 on a 0-10 scale.
Despite the demonstrable room for improvement in psoriatic arthritis treatment outcomes, better times are likely to be coming for affected patients. A record-breaking number of publications on psoriatic arthritis was published in 2017, and three additional drugs received marketing approval for the disease.
Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2018
Bloating. Flatulence. Think SIBO
MAUI, HAWAII – Recognition and effective treatment of small intestinal bowel overgrowth – aka, SIBO – is a highly practical skillset for nongastroenterologists to possess, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
SIBO is a common accompaniment to a range of chronic diseases, especially as patients age. And it’s not a condition that warrants referral to a gastroenterologist, according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
“To diagnose SIBO properly you need to do a carbohydrate breath test. Those tests are notoriously inaccurate, and it’s not worth it. We just treat. If we think you have SIBO, you do a course of rifaximin. And you can do the same,” she told her audience of rheumatologists.
There is an alternative diagnostic test. It involves obtaining a jejunal aspirate culture that demonstrates a bacterial concentration of more than 1,000 colony-forming units/mL. That’s an invasive and expensive test. Given how common SIBO symptoms are in patients with various underlying chronic diseases and the highly favorable risk/benefit ratio of a course of rifaximin, it’s entirely reasonable to skip formal diagnostic testing and treat empirically when the clinical picture is consistent with SIBO, according to the gastroenterologist.
The etiology of SIBO involves diminished intestinal motility and altered mucosal defenses. With reduced GI motility, the small bowel can’t get cleared of debris efficiently. Colonic microbes grab a foothold and bloom. Conditions marked by diminished intestinal motility – and high rates of SIBO – include scleroderma, diabetes, irritable bowel syndrome, chronic pancreatitis, cirrhosis, common variable immunodeficiency, HIV infection, and radiation enteritis. Small bowel diverticula are a setup for SIBO. Long-term proton pump inhibitor–therapy fosters hypochlorydia, which promotes SIBO. Opioid therapy is another common cause of SIBO.
So is bariatric surgery. “Bariatric surgery has caused so much iatrogenic GI disease, it’s just amazing. There is bacterial overgrowth in that population, and it’s a lot more complex than basic SIBO,” Dr. Mahadevan said.
SIBO causes malabsorption across the intestinal microvillus membrane as a result of damage to enterocytes, as well as impaired digestion in the intestinal lumen.
The presenting hallmark symptoms of SIBO are bloating, flatulence, early satiety, abdominal discomfort, and in some cases chronic diarrhea.
“You get a lot of gas and bloating. Patients will say, ‘I eat a small amount and feel full; I look like I’m pregnant; I have a lot of gas. What’s wrong with me?’ Chances are they have SIBO,” Dr. Mahadevan said. “The older you get the more SIBO you have.”
First-line treatment, aimed at diminishing small bowel bacteria, is rifaximin at 550 mg three times per day for 10-14 days.
“This is a very low-risk antibiotic. And it’s very effective for SIBO, but patients may need multiple courses,” according to the gastroenterologist.
Indeed, 40% of patients will experience recurrent SIBO symptoms within 9 months after a round of rifaximin. Recurrences are more common in patients on chronic proton pump–inhibitor therapy, the elderly, and those who have undergone appendectomy. Such patients may need another course of rifaximin once or twice per year.
“If they need rifaximin every 6 months, fine. Patients will be so grateful to you for that course of rifaximin,” Dr. Mahadevan said.
Patients with methane-predominant bacterial overgrowth, as opposed to hydrogen-predominant overgrowth, often benefit from concomitant neomycin at 500 mg twice per day along with their 10-14 days of rifaximin.
“A lot of our cirrhotic patients are on both,” she noted.
Alternatives to rifaximin include amoxicillin/clavulanic acid in combination with metronidazole.
Two measures she routinely recommends to forestall recurrent SIBO are to have patients start probiotics after a course of rifaximin, and also to try the low-FODMAP (fermentable oligo-di-monosaccharides and polyols) diet. The evidence base in SIBO is weak, but the anecdotal experience has been strongly positive.
“These are two interventions you can provide to your patients with a lot of bloating and gas. It’ll make them feel much, much better,” the gastroenterologist said.
FODMAPs are short-chain carbohydrates, and the low-FODMAP diet is an elimination diet. The first 6 weeks are highly restrictive, then the foods on the high FODMAP list are reintroduced one at a time until the offenders are identified. The low-FODMAP diet hasn’t been conclusively proven effective for SIBO in a randomized clinical trial, but it does have a compelling evidence base for treatment of irritable bowel syndrome diarrhea (J Gastroenterol Hepatol. 2010 Feb;25[2]:252-8).
“Anecdotally, the use of a low-FODMAP diet in patients with bloating and gas is very effective as well. Patients have a good deal of success with it,” she said.
Audience members were eager to learn what particular specific probiotic microorganism Dr. Madahaven recommends.
“I think the more we understand the microbiome, the further away I’m going from specific probiotics because it’s just too complex for any one probiotic to be effective. I tell patients to try to get it from their diet: yogurt or kefir with live bacteria. That’s what I use now,” she replied.
MAUI, HAWAII – Recognition and effective treatment of small intestinal bowel overgrowth – aka, SIBO – is a highly practical skillset for nongastroenterologists to possess, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
SIBO is a common accompaniment to a range of chronic diseases, especially as patients age. And it’s not a condition that warrants referral to a gastroenterologist, according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
“To diagnose SIBO properly you need to do a carbohydrate breath test. Those tests are notoriously inaccurate, and it’s not worth it. We just treat. If we think you have SIBO, you do a course of rifaximin. And you can do the same,” she told her audience of rheumatologists.
There is an alternative diagnostic test. It involves obtaining a jejunal aspirate culture that demonstrates a bacterial concentration of more than 1,000 colony-forming units/mL. That’s an invasive and expensive test. Given how common SIBO symptoms are in patients with various underlying chronic diseases and the highly favorable risk/benefit ratio of a course of rifaximin, it’s entirely reasonable to skip formal diagnostic testing and treat empirically when the clinical picture is consistent with SIBO, according to the gastroenterologist.
The etiology of SIBO involves diminished intestinal motility and altered mucosal defenses. With reduced GI motility, the small bowel can’t get cleared of debris efficiently. Colonic microbes grab a foothold and bloom. Conditions marked by diminished intestinal motility – and high rates of SIBO – include scleroderma, diabetes, irritable bowel syndrome, chronic pancreatitis, cirrhosis, common variable immunodeficiency, HIV infection, and radiation enteritis. Small bowel diverticula are a setup for SIBO. Long-term proton pump inhibitor–therapy fosters hypochlorydia, which promotes SIBO. Opioid therapy is another common cause of SIBO.
So is bariatric surgery. “Bariatric surgery has caused so much iatrogenic GI disease, it’s just amazing. There is bacterial overgrowth in that population, and it’s a lot more complex than basic SIBO,” Dr. Mahadevan said.
SIBO causes malabsorption across the intestinal microvillus membrane as a result of damage to enterocytes, as well as impaired digestion in the intestinal lumen.
The presenting hallmark symptoms of SIBO are bloating, flatulence, early satiety, abdominal discomfort, and in some cases chronic diarrhea.
“You get a lot of gas and bloating. Patients will say, ‘I eat a small amount and feel full; I look like I’m pregnant; I have a lot of gas. What’s wrong with me?’ Chances are they have SIBO,” Dr. Mahadevan said. “The older you get the more SIBO you have.”
First-line treatment, aimed at diminishing small bowel bacteria, is rifaximin at 550 mg three times per day for 10-14 days.
“This is a very low-risk antibiotic. And it’s very effective for SIBO, but patients may need multiple courses,” according to the gastroenterologist.
Indeed, 40% of patients will experience recurrent SIBO symptoms within 9 months after a round of rifaximin. Recurrences are more common in patients on chronic proton pump–inhibitor therapy, the elderly, and those who have undergone appendectomy. Such patients may need another course of rifaximin once or twice per year.
“If they need rifaximin every 6 months, fine. Patients will be so grateful to you for that course of rifaximin,” Dr. Mahadevan said.
Patients with methane-predominant bacterial overgrowth, as opposed to hydrogen-predominant overgrowth, often benefit from concomitant neomycin at 500 mg twice per day along with their 10-14 days of rifaximin.
“A lot of our cirrhotic patients are on both,” she noted.
Alternatives to rifaximin include amoxicillin/clavulanic acid in combination with metronidazole.
Two measures she routinely recommends to forestall recurrent SIBO are to have patients start probiotics after a course of rifaximin, and also to try the low-FODMAP (fermentable oligo-di-monosaccharides and polyols) diet. The evidence base in SIBO is weak, but the anecdotal experience has been strongly positive.
“These are two interventions you can provide to your patients with a lot of bloating and gas. It’ll make them feel much, much better,” the gastroenterologist said.
FODMAPs are short-chain carbohydrates, and the low-FODMAP diet is an elimination diet. The first 6 weeks are highly restrictive, then the foods on the high FODMAP list are reintroduced one at a time until the offenders are identified. The low-FODMAP diet hasn’t been conclusively proven effective for SIBO in a randomized clinical trial, but it does have a compelling evidence base for treatment of irritable bowel syndrome diarrhea (J Gastroenterol Hepatol. 2010 Feb;25[2]:252-8).
“Anecdotally, the use of a low-FODMAP diet in patients with bloating and gas is very effective as well. Patients have a good deal of success with it,” she said.
Audience members were eager to learn what particular specific probiotic microorganism Dr. Madahaven recommends.
“I think the more we understand the microbiome, the further away I’m going from specific probiotics because it’s just too complex for any one probiotic to be effective. I tell patients to try to get it from their diet: yogurt or kefir with live bacteria. That’s what I use now,” she replied.
MAUI, HAWAII – Recognition and effective treatment of small intestinal bowel overgrowth – aka, SIBO – is a highly practical skillset for nongastroenterologists to possess, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
SIBO is a common accompaniment to a range of chronic diseases, especially as patients age. And it’s not a condition that warrants referral to a gastroenterologist, according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
“To diagnose SIBO properly you need to do a carbohydrate breath test. Those tests are notoriously inaccurate, and it’s not worth it. We just treat. If we think you have SIBO, you do a course of rifaximin. And you can do the same,” she told her audience of rheumatologists.
There is an alternative diagnostic test. It involves obtaining a jejunal aspirate culture that demonstrates a bacterial concentration of more than 1,000 colony-forming units/mL. That’s an invasive and expensive test. Given how common SIBO symptoms are in patients with various underlying chronic diseases and the highly favorable risk/benefit ratio of a course of rifaximin, it’s entirely reasonable to skip formal diagnostic testing and treat empirically when the clinical picture is consistent with SIBO, according to the gastroenterologist.
The etiology of SIBO involves diminished intestinal motility and altered mucosal defenses. With reduced GI motility, the small bowel can’t get cleared of debris efficiently. Colonic microbes grab a foothold and bloom. Conditions marked by diminished intestinal motility – and high rates of SIBO – include scleroderma, diabetes, irritable bowel syndrome, chronic pancreatitis, cirrhosis, common variable immunodeficiency, HIV infection, and radiation enteritis. Small bowel diverticula are a setup for SIBO. Long-term proton pump inhibitor–therapy fosters hypochlorydia, which promotes SIBO. Opioid therapy is another common cause of SIBO.
So is bariatric surgery. “Bariatric surgery has caused so much iatrogenic GI disease, it’s just amazing. There is bacterial overgrowth in that population, and it’s a lot more complex than basic SIBO,” Dr. Mahadevan said.
SIBO causes malabsorption across the intestinal microvillus membrane as a result of damage to enterocytes, as well as impaired digestion in the intestinal lumen.
The presenting hallmark symptoms of SIBO are bloating, flatulence, early satiety, abdominal discomfort, and in some cases chronic diarrhea.
“You get a lot of gas and bloating. Patients will say, ‘I eat a small amount and feel full; I look like I’m pregnant; I have a lot of gas. What’s wrong with me?’ Chances are they have SIBO,” Dr. Mahadevan said. “The older you get the more SIBO you have.”
First-line treatment, aimed at diminishing small bowel bacteria, is rifaximin at 550 mg three times per day for 10-14 days.
“This is a very low-risk antibiotic. And it’s very effective for SIBO, but patients may need multiple courses,” according to the gastroenterologist.
Indeed, 40% of patients will experience recurrent SIBO symptoms within 9 months after a round of rifaximin. Recurrences are more common in patients on chronic proton pump–inhibitor therapy, the elderly, and those who have undergone appendectomy. Such patients may need another course of rifaximin once or twice per year.
“If they need rifaximin every 6 months, fine. Patients will be so grateful to you for that course of rifaximin,” Dr. Mahadevan said.
Patients with methane-predominant bacterial overgrowth, as opposed to hydrogen-predominant overgrowth, often benefit from concomitant neomycin at 500 mg twice per day along with their 10-14 days of rifaximin.
“A lot of our cirrhotic patients are on both,” she noted.
Alternatives to rifaximin include amoxicillin/clavulanic acid in combination with metronidazole.
Two measures she routinely recommends to forestall recurrent SIBO are to have patients start probiotics after a course of rifaximin, and also to try the low-FODMAP (fermentable oligo-di-monosaccharides and polyols) diet. The evidence base in SIBO is weak, but the anecdotal experience has been strongly positive.
“These are two interventions you can provide to your patients with a lot of bloating and gas. It’ll make them feel much, much better,” the gastroenterologist said.
FODMAPs are short-chain carbohydrates, and the low-FODMAP diet is an elimination diet. The first 6 weeks are highly restrictive, then the foods on the high FODMAP list are reintroduced one at a time until the offenders are identified. The low-FODMAP diet hasn’t been conclusively proven effective for SIBO in a randomized clinical trial, but it does have a compelling evidence base for treatment of irritable bowel syndrome diarrhea (J Gastroenterol Hepatol. 2010 Feb;25[2]:252-8).
“Anecdotally, the use of a low-FODMAP diet in patients with bloating and gas is very effective as well. Patients have a good deal of success with it,” she said.
Audience members were eager to learn what particular specific probiotic microorganism Dr. Madahaven recommends.
“I think the more we understand the microbiome, the further away I’m going from specific probiotics because it’s just too complex for any one probiotic to be effective. I tell patients to try to get it from their diet: yogurt or kefir with live bacteria. That’s what I use now,” she replied.
EXPERT ANALYSIS FROM RWCS 2018
Mast cell synovitis: potential target in RA?
MAUI, HAWAII – Could mast cell-rich synovitis become a novel target in patients with early rheumatoid arthritis?
Investigators at the University of London believe so. In a small but provocative study presented at the 2017 annual meeting of the American College of Rheumatology, they demonstrated that these mast cells are not an innocent bystander in joint inflammation; rather, they play an active albeit still incompletely understood role in the synovial inflammatory infiltrate and in disease progression, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
Treatment with synthetic DMARDs was partially effective, both clinically and at the cellular level. Mean mast cell density fell from 14.2/mm2 at baseline to 8.2/mm2 at 6 months. But synovial mast cells were still present at 6 months in 9 of 20 patients. Those nine patients had significantly higher DAS28 scores – a mean of 4.08 versus 2.41 in the synovial mast cell–negative group – as well as higher synovitis scores. Disease remission as defined by a DAS28 score below 2.6 was achieved in only 2 of 9 patients with persistent mast cell-rich synovitis, as compared with 8 of 11 mast cell-negative patients.
Moreover, four of the nine patients with persistent mast cell-rich synovitis after 6 months of synthetic DMARDs had synovial lymphoid aggregates of CD20-positive B cells and/or CD138-positive plasma cells; in contrast, none of the 11 synovial mast cell-negative patients did, noted Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is in private practice in Santa Monica, Calif.
In theory, if a baseline synovial tissue immune cell profile could be identified that’s predictive of high-level responsiveness to synthetic DMARDs or, conversely, nonresponsiveness, tissue specimens could be used to stratify patients with early RA to different initial treatment strategies. The problem with that is few rheumatologists in the United States – and indeed worldwide – are proficient at performing ultrasound-guided synovial biopsies, according to Dr. Troum.
His description of the London study prompted a question as to whether any of the biologics used in rheumatology can inhibit mast cells. Arthur Kavanaugh, MD, symposium director, said the only agent that comes to mind is imatinib (Gleevec), a tyrosine kinase inhibitor used in the treatment of aggressive systemic mastocytosis as well as for certain leukemias.
“It has a ton of toxicity, though,” said Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.
Dr. Troum reported having no financial conflicts regarding his presentation.
MAUI, HAWAII – Could mast cell-rich synovitis become a novel target in patients with early rheumatoid arthritis?
Investigators at the University of London believe so. In a small but provocative study presented at the 2017 annual meeting of the American College of Rheumatology, they demonstrated that these mast cells are not an innocent bystander in joint inflammation; rather, they play an active albeit still incompletely understood role in the synovial inflammatory infiltrate and in disease progression, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
Treatment with synthetic DMARDs was partially effective, both clinically and at the cellular level. Mean mast cell density fell from 14.2/mm2 at baseline to 8.2/mm2 at 6 months. But synovial mast cells were still present at 6 months in 9 of 20 patients. Those nine patients had significantly higher DAS28 scores – a mean of 4.08 versus 2.41 in the synovial mast cell–negative group – as well as higher synovitis scores. Disease remission as defined by a DAS28 score below 2.6 was achieved in only 2 of 9 patients with persistent mast cell-rich synovitis, as compared with 8 of 11 mast cell-negative patients.
Moreover, four of the nine patients with persistent mast cell-rich synovitis after 6 months of synthetic DMARDs had synovial lymphoid aggregates of CD20-positive B cells and/or CD138-positive plasma cells; in contrast, none of the 11 synovial mast cell-negative patients did, noted Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is in private practice in Santa Monica, Calif.
In theory, if a baseline synovial tissue immune cell profile could be identified that’s predictive of high-level responsiveness to synthetic DMARDs or, conversely, nonresponsiveness, tissue specimens could be used to stratify patients with early RA to different initial treatment strategies. The problem with that is few rheumatologists in the United States – and indeed worldwide – are proficient at performing ultrasound-guided synovial biopsies, according to Dr. Troum.
His description of the London study prompted a question as to whether any of the biologics used in rheumatology can inhibit mast cells. Arthur Kavanaugh, MD, symposium director, said the only agent that comes to mind is imatinib (Gleevec), a tyrosine kinase inhibitor used in the treatment of aggressive systemic mastocytosis as well as for certain leukemias.
“It has a ton of toxicity, though,” said Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.
Dr. Troum reported having no financial conflicts regarding his presentation.
MAUI, HAWAII – Could mast cell-rich synovitis become a novel target in patients with early rheumatoid arthritis?
Investigators at the University of London believe so. In a small but provocative study presented at the 2017 annual meeting of the American College of Rheumatology, they demonstrated that these mast cells are not an innocent bystander in joint inflammation; rather, they play an active albeit still incompletely understood role in the synovial inflammatory infiltrate and in disease progression, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
Treatment with synthetic DMARDs was partially effective, both clinically and at the cellular level. Mean mast cell density fell from 14.2/mm2 at baseline to 8.2/mm2 at 6 months. But synovial mast cells were still present at 6 months in 9 of 20 patients. Those nine patients had significantly higher DAS28 scores – a mean of 4.08 versus 2.41 in the synovial mast cell–negative group – as well as higher synovitis scores. Disease remission as defined by a DAS28 score below 2.6 was achieved in only 2 of 9 patients with persistent mast cell-rich synovitis, as compared with 8 of 11 mast cell-negative patients.
Moreover, four of the nine patients with persistent mast cell-rich synovitis after 6 months of synthetic DMARDs had synovial lymphoid aggregates of CD20-positive B cells and/or CD138-positive plasma cells; in contrast, none of the 11 synovial mast cell-negative patients did, noted Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is in private practice in Santa Monica, Calif.
In theory, if a baseline synovial tissue immune cell profile could be identified that’s predictive of high-level responsiveness to synthetic DMARDs or, conversely, nonresponsiveness, tissue specimens could be used to stratify patients with early RA to different initial treatment strategies. The problem with that is few rheumatologists in the United States – and indeed worldwide – are proficient at performing ultrasound-guided synovial biopsies, according to Dr. Troum.
His description of the London study prompted a question as to whether any of the biologics used in rheumatology can inhibit mast cells. Arthur Kavanaugh, MD, symposium director, said the only agent that comes to mind is imatinib (Gleevec), a tyrosine kinase inhibitor used in the treatment of aggressive systemic mastocytosis as well as for certain leukemias.
“It has a ton of toxicity, though,” said Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.
Dr. Troum reported having no financial conflicts regarding his presentation.
EXPERT ANALYSIS FROM RWCS 2018
How to direct refer for GI endoscopy
MAUI, HAWAII – Rheumatologists can save their patients time and the inconvenience of an unnecessary preprocedural office visit with a gastroenterologist by making a direct referral for GI endoscopy when appropriate, according to Uma Mahadevan, MD, professor of medicine at the University of California, San Francisco.
“Many health systems have access issues, and in most accountable care organizations, there’s a need to see patients within 14 days. the gastroenterologist explained at the 2018 Rheumatology Winter Clinical Symposium.
“We’re an open-access endoscopy center at UCSF, and I can’t tell you how many times a patient gets direct referred to us and – the night before the procedure, when we’re preparing for the case – we see that this patient can’t have a procedure tomorrow. Those patients have already done the bowel prep, they’re taking the day off work, they’ve arranged for someone to drive them, and they’re really mad,” said Dr. Mahadevan, who is also the medical director of the UCSF Center for Colitis and Crohn’s Disease.
Sometimes the procedure gets called off because the gastroenterologist sees that it would be inappropriate. For example, it would be inappropriate to perform an endoscopy on a patient with irritable bowel syndrome or fibromyalgia who has already had three negative endoscopic procedures in the past 5 years; alternatively, a screening colonoscopy would be inappropriate for an 80-year-old because the U.S. Preventive Services Task Force gives a class A recommendation for screening colonoscopy only during ages 50-75 years.
Sometimes the physician who made the direct referral failed to include other key information the gastroenterologist needed to have in advance of the procedure. For example, a morbidly obese patient or an individual with significant cardiovascular or pulmonary disease generally needs to have an anesthesiologist present for GI endoscopy, rather than a nurse anesthetist, since the airway is suspect. Similarly, a patient with a severe anxiety disorder or tolerance to pain medication is unlikely to be adequately sedated with the fentanyl and midazolam (Versed) used for moderate sedation in most upper endoscopy and colonoscopy procedures; those individuals are going to require deep sedation with propofol (Diprivan) and assistance in maintaining a patent airway.
“Your patient taking Oxycodone every day is not going to get sedated with fentanyl and midazolam. So you need to put that information on your direct request,” she stressed.
“If your patient has obstructive sleep apnea and is on CPAP at home, or if your patient is on home oxygen, your gastroenterologist needs to know that because those are the patients we bring into the office to evaluate the airway ahead of time,” according to the gastroenterologist.
Also, while routine direct referral for colonoscopy to rule out comorbid inflammatory bowel disease is entirely appropriate in patients with ankylosing spondylitis or other spondyloarthropathies, if they had ankylosing spondylitis in the prebiologic era, then it’s important to include that information.
“If they did, their neck is often dangerous for sedation. They’re very difficult to intubate. That’s something we need to know,” Dr. Mahadevan continued.
Other patient information gastroenterologists want included in the direct referral: Is the patient on daily aspirin and/or a thienopyridine antiplatelet agent or on oral anticoagulation with warfarin or one of the newer direct-acting oral anticoagulants? American Society for Gastrointestinal Endoscopy guidelines have detailed how to manage antithrombotic agents in patients undergoing GI endoscopy, including when and how to bridge with low-molecular-weight heparin in the days prior to the procedure (Gastrointest Endosc. 2016 Jan;83[1]:3-16). Of note, the guidelines rate diagnostic esophagogastroduodenoscopy (EGD) and colonoscopy, even with biopsies taken, as low-bleeding-risk procedures that therefore don’t require stopping antithrombotic therapy.
In addition to screening or surveillance colonoscopy, rheumatologists might also direct refer patients for GI endoscopy because they have iron-deficiency anemia, in which case evaluation by both EGD and colonoscopy is necessary. Direct referral for EGD in patients with celiac disease is appropriate. Acute GI bleeding is best handled via direct referral for colonoscopy in a patient with hematochezia and for EGD in the setting of melena. Direct referral for endoscopy is also warranted in patients with polymyalgia rheumatica or dermatomyositis, where the indication is to rule out associated malignancy.
Dr. Mahadevan reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – Rheumatologists can save their patients time and the inconvenience of an unnecessary preprocedural office visit with a gastroenterologist by making a direct referral for GI endoscopy when appropriate, according to Uma Mahadevan, MD, professor of medicine at the University of California, San Francisco.
“Many health systems have access issues, and in most accountable care organizations, there’s a need to see patients within 14 days. the gastroenterologist explained at the 2018 Rheumatology Winter Clinical Symposium.
“We’re an open-access endoscopy center at UCSF, and I can’t tell you how many times a patient gets direct referred to us and – the night before the procedure, when we’re preparing for the case – we see that this patient can’t have a procedure tomorrow. Those patients have already done the bowel prep, they’re taking the day off work, they’ve arranged for someone to drive them, and they’re really mad,” said Dr. Mahadevan, who is also the medical director of the UCSF Center for Colitis and Crohn’s Disease.
Sometimes the procedure gets called off because the gastroenterologist sees that it would be inappropriate. For example, it would be inappropriate to perform an endoscopy on a patient with irritable bowel syndrome or fibromyalgia who has already had three negative endoscopic procedures in the past 5 years; alternatively, a screening colonoscopy would be inappropriate for an 80-year-old because the U.S. Preventive Services Task Force gives a class A recommendation for screening colonoscopy only during ages 50-75 years.
Sometimes the physician who made the direct referral failed to include other key information the gastroenterologist needed to have in advance of the procedure. For example, a morbidly obese patient or an individual with significant cardiovascular or pulmonary disease generally needs to have an anesthesiologist present for GI endoscopy, rather than a nurse anesthetist, since the airway is suspect. Similarly, a patient with a severe anxiety disorder or tolerance to pain medication is unlikely to be adequately sedated with the fentanyl and midazolam (Versed) used for moderate sedation in most upper endoscopy and colonoscopy procedures; those individuals are going to require deep sedation with propofol (Diprivan) and assistance in maintaining a patent airway.
“Your patient taking Oxycodone every day is not going to get sedated with fentanyl and midazolam. So you need to put that information on your direct request,” she stressed.
“If your patient has obstructive sleep apnea and is on CPAP at home, or if your patient is on home oxygen, your gastroenterologist needs to know that because those are the patients we bring into the office to evaluate the airway ahead of time,” according to the gastroenterologist.
Also, while routine direct referral for colonoscopy to rule out comorbid inflammatory bowel disease is entirely appropriate in patients with ankylosing spondylitis or other spondyloarthropathies, if they had ankylosing spondylitis in the prebiologic era, then it’s important to include that information.
“If they did, their neck is often dangerous for sedation. They’re very difficult to intubate. That’s something we need to know,” Dr. Mahadevan continued.
Other patient information gastroenterologists want included in the direct referral: Is the patient on daily aspirin and/or a thienopyridine antiplatelet agent or on oral anticoagulation with warfarin or one of the newer direct-acting oral anticoagulants? American Society for Gastrointestinal Endoscopy guidelines have detailed how to manage antithrombotic agents in patients undergoing GI endoscopy, including when and how to bridge with low-molecular-weight heparin in the days prior to the procedure (Gastrointest Endosc. 2016 Jan;83[1]:3-16). Of note, the guidelines rate diagnostic esophagogastroduodenoscopy (EGD) and colonoscopy, even with biopsies taken, as low-bleeding-risk procedures that therefore don’t require stopping antithrombotic therapy.
In addition to screening or surveillance colonoscopy, rheumatologists might also direct refer patients for GI endoscopy because they have iron-deficiency anemia, in which case evaluation by both EGD and colonoscopy is necessary. Direct referral for EGD in patients with celiac disease is appropriate. Acute GI bleeding is best handled via direct referral for colonoscopy in a patient with hematochezia and for EGD in the setting of melena. Direct referral for endoscopy is also warranted in patients with polymyalgia rheumatica or dermatomyositis, where the indication is to rule out associated malignancy.
Dr. Mahadevan reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – Rheumatologists can save their patients time and the inconvenience of an unnecessary preprocedural office visit with a gastroenterologist by making a direct referral for GI endoscopy when appropriate, according to Uma Mahadevan, MD, professor of medicine at the University of California, San Francisco.
“Many health systems have access issues, and in most accountable care organizations, there’s a need to see patients within 14 days. the gastroenterologist explained at the 2018 Rheumatology Winter Clinical Symposium.
“We’re an open-access endoscopy center at UCSF, and I can’t tell you how many times a patient gets direct referred to us and – the night before the procedure, when we’re preparing for the case – we see that this patient can’t have a procedure tomorrow. Those patients have already done the bowel prep, they’re taking the day off work, they’ve arranged for someone to drive them, and they’re really mad,” said Dr. Mahadevan, who is also the medical director of the UCSF Center for Colitis and Crohn’s Disease.
Sometimes the procedure gets called off because the gastroenterologist sees that it would be inappropriate. For example, it would be inappropriate to perform an endoscopy on a patient with irritable bowel syndrome or fibromyalgia who has already had three negative endoscopic procedures in the past 5 years; alternatively, a screening colonoscopy would be inappropriate for an 80-year-old because the U.S. Preventive Services Task Force gives a class A recommendation for screening colonoscopy only during ages 50-75 years.
Sometimes the physician who made the direct referral failed to include other key information the gastroenterologist needed to have in advance of the procedure. For example, a morbidly obese patient or an individual with significant cardiovascular or pulmonary disease generally needs to have an anesthesiologist present for GI endoscopy, rather than a nurse anesthetist, since the airway is suspect. Similarly, a patient with a severe anxiety disorder or tolerance to pain medication is unlikely to be adequately sedated with the fentanyl and midazolam (Versed) used for moderate sedation in most upper endoscopy and colonoscopy procedures; those individuals are going to require deep sedation with propofol (Diprivan) and assistance in maintaining a patent airway.
“Your patient taking Oxycodone every day is not going to get sedated with fentanyl and midazolam. So you need to put that information on your direct request,” she stressed.
“If your patient has obstructive sleep apnea and is on CPAP at home, or if your patient is on home oxygen, your gastroenterologist needs to know that because those are the patients we bring into the office to evaluate the airway ahead of time,” according to the gastroenterologist.
Also, while routine direct referral for colonoscopy to rule out comorbid inflammatory bowel disease is entirely appropriate in patients with ankylosing spondylitis or other spondyloarthropathies, if they had ankylosing spondylitis in the prebiologic era, then it’s important to include that information.
“If they did, their neck is often dangerous for sedation. They’re very difficult to intubate. That’s something we need to know,” Dr. Mahadevan continued.
Other patient information gastroenterologists want included in the direct referral: Is the patient on daily aspirin and/or a thienopyridine antiplatelet agent or on oral anticoagulation with warfarin or one of the newer direct-acting oral anticoagulants? American Society for Gastrointestinal Endoscopy guidelines have detailed how to manage antithrombotic agents in patients undergoing GI endoscopy, including when and how to bridge with low-molecular-weight heparin in the days prior to the procedure (Gastrointest Endosc. 2016 Jan;83[1]:3-16). Of note, the guidelines rate diagnostic esophagogastroduodenoscopy (EGD) and colonoscopy, even with biopsies taken, as low-bleeding-risk procedures that therefore don’t require stopping antithrombotic therapy.
In addition to screening or surveillance colonoscopy, rheumatologists might also direct refer patients for GI endoscopy because they have iron-deficiency anemia, in which case evaluation by both EGD and colonoscopy is necessary. Direct referral for EGD in patients with celiac disease is appropriate. Acute GI bleeding is best handled via direct referral for colonoscopy in a patient with hematochezia and for EGD in the setting of melena. Direct referral for endoscopy is also warranted in patients with polymyalgia rheumatica or dermatomyositis, where the indication is to rule out associated malignancy.
Dr. Mahadevan reported having no financial conflicts regarding her presentation.
EXPERT ANALYSIS FROM RWCS 2018
Role of musculoskeletal ultrasound expands in rheumatic diseases
MAUI, HAWAII – Recent studies highlight novel applications of musculoskeletal ultrasound across a broad spectrum of rheumatic diseases beyond the imaging method’s well-established role in diagnosis and follow-up of patients with rheumatoid arthritis, Alvin F. Wells, MD, PhD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited recently published evidence in support of his contention:
Systemic lupus erythematosus
Portuguese investigators reported that 77% of their study participants with asymptomatic systemic lupus erythematosus (SLE) – that is, no arthralgia or musculoskeletal signs or symptoms on physical examination – demonstrated gray-scale ultrasound evidence of grade 1 or greater synovial hypertrophy of joints in the hands and/or wrists on a semiquantitative 0-3 scale. So did 100% of patients with symptomatic SLE in this small study, in which physicians evaluated 22 joints per person.
Moreover, grade 1 or greater intra-articular power Doppler changes were also detected in one-fifth of the asymptomatic patients and 83% of those with symptomatic SLE. What the researchers considered persuasive ultrasound evidence of synovitis – grade 2 or 3 synovial hypertrophy or at least grade 1 power Doppler findings – was noted in 23% of the asymptomatic SLE patients, 83% of those who were symptomatic, and none of the healthy controls.
The investigators concluded that asymptomatic patients with SLE may present with subclinical joint inflammation that often goes undetected by physical examination and x-ray. They added that ultrasound with power Doppler may be important in disease evaluation and therapeutic monitoring in patients with lupus (Lupus Sci Med. 2017 Jan 19;4[1]:e000184).
For Dr. Wells, the take-home message was clear: “Don’t overlook the hands.”
“In my lupus patients, sure, I look at the hips, making sure there are no subtle signs of osteonecrosis, but I think we often forget to look at the hands. We’re looking at the hair, looking at the mouth, we’re worried about the lungs. But I think we often overlook the synovitis. These patients are going to the ER because they’re having pain in their hands, and they’re getting told, ‘This is fibromyalgia, go back and see your rheumatologist.’ So it’s something to think about: When you’ve got a patient with active lupus, ultrasound may have a role to play,” according to Dr. Wells.
The big unanswered question is whether early aggressive treatment in SLE patients with these synovial abnormalities – that is, a treat-to-target, ultrasound-guided strategy – can limit erosive changes, avoid disease progression, and improve functional outcomes, as is now known to be the case in RA. Long-term studies will be required to find out, he noted.
Ultrasound of parotid glands in suspected Sjögren’s syndrome is biopsy sparing
Members of the European League Against Rheumatism Ultrasound Primary Sjögren’s Syndrome Study Group recently reported that in a prospective study of 103 consecutive outpatients with clinically suspected primary Sjögren’s syndrome, a positive ultrasound examination of the major salivary glands in combination with the presence of anti-SSA/Ro antibodies was highly predictive of positive parotid and labial gland biopsies. Indeed, a positive ultrasound plus anti-SSA/Ro antibodies showed a high predictive value for Sjögren’s syndrome regardless of whether the classification was based upon American College of Rheumatology, American European Consensus Group, or ACR-EULAR criteria (Ann Rheum Dis. 2017;76[11]:1883-9).
“Ophthalmologists, dentists, and primary care physicians frequently refer patients with dry eyes and dry mouth to us to sort out whether they have Sjögren’s syndrome. The data show now that with a positive salivary gland ultrasound score and a positive anti-SSA/Ro antibody test you can avoid the biopsies,” the rheumatologist said.
That’s a fine thing for patients because these biopsies often result in residual numbness and tingling, he added.
Dr. Wells noted that a multicenter European group recently fine-tuned the criteria for an abnormal salivary gland ultrasound score. They identified echogenicity and homogeneity as the two most reliable items on the score. They also reported that the mean time it took five ultrasonographers to perform salivary gland assessments was reasonable at 11-27 minutes (RMD Open. 2017 Jun 9;3[1]:e000364).
“You can do this essentially in an office visit. The changes in the salivary glands are pathognomonic for Sjögren’s – you won’t get it confused with a neoplasm. I schedule these patients for a 15-minute time slot, and based upon the ultrasound and whether they’re positive or negative for anti-SSA/Ro antibodies I can make some decisions from there,” Dr. Wells explained.
He described what to look for on ultrasound: “A normal parotid looks like a homogeneous gray sponge on ultrasound. In Sjögren’s syndrome, you see icepicklike holes in the sponge. And there’s thickening of the intima, so you see blunting of the arterial wave on pulse wave.”
Implications of ultrasound enthesitis in early spondyloarthritis
French rheumatologists reported on the implications of an ultrasound peripheral enthesis assessment in 402 patients with early axial spondyloarthritis in the French DESIR cohort. The ultrasound evaluation covered the lateral epicondyles, Achilles tendon, and superior and inferior patellar ligament entheses. The results were summed up in ultrasound structural and power Doppler scores. In addition, the investigators obtained spine and sacroiliac joint MRI scans and spine x-rays, all scored centrally.
It turned out that ultrasound abnormalities weren’t useful in monitoring axial spondyloarthritis clinical disease activity as reflected in Bath Ankylosing Spondylitis Disease Activity Index scores, nor were the ultrasound structural and power Doppler scores associated with MRI spine inflammatory lesions or sacroiliitis. However, ultrasound enthesophytes were strongly associated with axial syndesmophytes, suggesting that these ultrasound abnormalities might be a marker of disease severity in axial spondyloarthritis (RMD Open. 2017 Sep 7;3[2]:e000482).
“Whether or not by inhibiting these peripheral enthesophytes you’ll ultimately inhibit further enthesophytes or syndesmophytes from forming is yet to be seen,” Dr. Wells cautioned.
He added, however, that a recent short-term, randomized, placebo-controlled trial in 185 patients with nonradiographic axial spondyloarthritis holds hope in that regard. Investigators in the ongoing multicenter EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic Spondyloarthritis) trial reported that treatment with etanercept was associated with a significantly greater reduction in erosions, an increase in backfill, and improved clinical outcomes, compared with placebo, as assessed by MRIs obtained at baseline and 12 weeks.
The investigators viewed these findings as consistent with an early reparative response to the anti–tumor necrosis factor agent, although they noted that understanding of the biologic agent’s true impact on disease progression awaits longer-term follow-up in the 104-week study (Ann Rheum Dis. 2018 Jan;77[1]:78-84).
Dr. Wells reported serving as a consultant to more than half a dozen pharmaceutical companies and receiving research funding from Abbott, Celgene, and UCB.
MAUI, HAWAII – Recent studies highlight novel applications of musculoskeletal ultrasound across a broad spectrum of rheumatic diseases beyond the imaging method’s well-established role in diagnosis and follow-up of patients with rheumatoid arthritis, Alvin F. Wells, MD, PhD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited recently published evidence in support of his contention:
Systemic lupus erythematosus
Portuguese investigators reported that 77% of their study participants with asymptomatic systemic lupus erythematosus (SLE) – that is, no arthralgia or musculoskeletal signs or symptoms on physical examination – demonstrated gray-scale ultrasound evidence of grade 1 or greater synovial hypertrophy of joints in the hands and/or wrists on a semiquantitative 0-3 scale. So did 100% of patients with symptomatic SLE in this small study, in which physicians evaluated 22 joints per person.
Moreover, grade 1 or greater intra-articular power Doppler changes were also detected in one-fifth of the asymptomatic patients and 83% of those with symptomatic SLE. What the researchers considered persuasive ultrasound evidence of synovitis – grade 2 or 3 synovial hypertrophy or at least grade 1 power Doppler findings – was noted in 23% of the asymptomatic SLE patients, 83% of those who were symptomatic, and none of the healthy controls.
The investigators concluded that asymptomatic patients with SLE may present with subclinical joint inflammation that often goes undetected by physical examination and x-ray. They added that ultrasound with power Doppler may be important in disease evaluation and therapeutic monitoring in patients with lupus (Lupus Sci Med. 2017 Jan 19;4[1]:e000184).
For Dr. Wells, the take-home message was clear: “Don’t overlook the hands.”
“In my lupus patients, sure, I look at the hips, making sure there are no subtle signs of osteonecrosis, but I think we often forget to look at the hands. We’re looking at the hair, looking at the mouth, we’re worried about the lungs. But I think we often overlook the synovitis. These patients are going to the ER because they’re having pain in their hands, and they’re getting told, ‘This is fibromyalgia, go back and see your rheumatologist.’ So it’s something to think about: When you’ve got a patient with active lupus, ultrasound may have a role to play,” according to Dr. Wells.
The big unanswered question is whether early aggressive treatment in SLE patients with these synovial abnormalities – that is, a treat-to-target, ultrasound-guided strategy – can limit erosive changes, avoid disease progression, and improve functional outcomes, as is now known to be the case in RA. Long-term studies will be required to find out, he noted.
Ultrasound of parotid glands in suspected Sjögren’s syndrome is biopsy sparing
Members of the European League Against Rheumatism Ultrasound Primary Sjögren’s Syndrome Study Group recently reported that in a prospective study of 103 consecutive outpatients with clinically suspected primary Sjögren’s syndrome, a positive ultrasound examination of the major salivary glands in combination with the presence of anti-SSA/Ro antibodies was highly predictive of positive parotid and labial gland biopsies. Indeed, a positive ultrasound plus anti-SSA/Ro antibodies showed a high predictive value for Sjögren’s syndrome regardless of whether the classification was based upon American College of Rheumatology, American European Consensus Group, or ACR-EULAR criteria (Ann Rheum Dis. 2017;76[11]:1883-9).
“Ophthalmologists, dentists, and primary care physicians frequently refer patients with dry eyes and dry mouth to us to sort out whether they have Sjögren’s syndrome. The data show now that with a positive salivary gland ultrasound score and a positive anti-SSA/Ro antibody test you can avoid the biopsies,” the rheumatologist said.
That’s a fine thing for patients because these biopsies often result in residual numbness and tingling, he added.
Dr. Wells noted that a multicenter European group recently fine-tuned the criteria for an abnormal salivary gland ultrasound score. They identified echogenicity and homogeneity as the two most reliable items on the score. They also reported that the mean time it took five ultrasonographers to perform salivary gland assessments was reasonable at 11-27 minutes (RMD Open. 2017 Jun 9;3[1]:e000364).
“You can do this essentially in an office visit. The changes in the salivary glands are pathognomonic for Sjögren’s – you won’t get it confused with a neoplasm. I schedule these patients for a 15-minute time slot, and based upon the ultrasound and whether they’re positive or negative for anti-SSA/Ro antibodies I can make some decisions from there,” Dr. Wells explained.
He described what to look for on ultrasound: “A normal parotid looks like a homogeneous gray sponge on ultrasound. In Sjögren’s syndrome, you see icepicklike holes in the sponge. And there’s thickening of the intima, so you see blunting of the arterial wave on pulse wave.”
Implications of ultrasound enthesitis in early spondyloarthritis
French rheumatologists reported on the implications of an ultrasound peripheral enthesis assessment in 402 patients with early axial spondyloarthritis in the French DESIR cohort. The ultrasound evaluation covered the lateral epicondyles, Achilles tendon, and superior and inferior patellar ligament entheses. The results were summed up in ultrasound structural and power Doppler scores. In addition, the investigators obtained spine and sacroiliac joint MRI scans and spine x-rays, all scored centrally.
It turned out that ultrasound abnormalities weren’t useful in monitoring axial spondyloarthritis clinical disease activity as reflected in Bath Ankylosing Spondylitis Disease Activity Index scores, nor were the ultrasound structural and power Doppler scores associated with MRI spine inflammatory lesions or sacroiliitis. However, ultrasound enthesophytes were strongly associated with axial syndesmophytes, suggesting that these ultrasound abnormalities might be a marker of disease severity in axial spondyloarthritis (RMD Open. 2017 Sep 7;3[2]:e000482).
“Whether or not by inhibiting these peripheral enthesophytes you’ll ultimately inhibit further enthesophytes or syndesmophytes from forming is yet to be seen,” Dr. Wells cautioned.
He added, however, that a recent short-term, randomized, placebo-controlled trial in 185 patients with nonradiographic axial spondyloarthritis holds hope in that regard. Investigators in the ongoing multicenter EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic Spondyloarthritis) trial reported that treatment with etanercept was associated with a significantly greater reduction in erosions, an increase in backfill, and improved clinical outcomes, compared with placebo, as assessed by MRIs obtained at baseline and 12 weeks.
The investigators viewed these findings as consistent with an early reparative response to the anti–tumor necrosis factor agent, although they noted that understanding of the biologic agent’s true impact on disease progression awaits longer-term follow-up in the 104-week study (Ann Rheum Dis. 2018 Jan;77[1]:78-84).
Dr. Wells reported serving as a consultant to more than half a dozen pharmaceutical companies and receiving research funding from Abbott, Celgene, and UCB.
MAUI, HAWAII – Recent studies highlight novel applications of musculoskeletal ultrasound across a broad spectrum of rheumatic diseases beyond the imaging method’s well-established role in diagnosis and follow-up of patients with rheumatoid arthritis, Alvin F. Wells, MD, PhD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited recently published evidence in support of his contention:
Systemic lupus erythematosus
Portuguese investigators reported that 77% of their study participants with asymptomatic systemic lupus erythematosus (SLE) – that is, no arthralgia or musculoskeletal signs or symptoms on physical examination – demonstrated gray-scale ultrasound evidence of grade 1 or greater synovial hypertrophy of joints in the hands and/or wrists on a semiquantitative 0-3 scale. So did 100% of patients with symptomatic SLE in this small study, in which physicians evaluated 22 joints per person.
Moreover, grade 1 or greater intra-articular power Doppler changes were also detected in one-fifth of the asymptomatic patients and 83% of those with symptomatic SLE. What the researchers considered persuasive ultrasound evidence of synovitis – grade 2 or 3 synovial hypertrophy or at least grade 1 power Doppler findings – was noted in 23% of the asymptomatic SLE patients, 83% of those who were symptomatic, and none of the healthy controls.
The investigators concluded that asymptomatic patients with SLE may present with subclinical joint inflammation that often goes undetected by physical examination and x-ray. They added that ultrasound with power Doppler may be important in disease evaluation and therapeutic monitoring in patients with lupus (Lupus Sci Med. 2017 Jan 19;4[1]:e000184).
For Dr. Wells, the take-home message was clear: “Don’t overlook the hands.”
“In my lupus patients, sure, I look at the hips, making sure there are no subtle signs of osteonecrosis, but I think we often forget to look at the hands. We’re looking at the hair, looking at the mouth, we’re worried about the lungs. But I think we often overlook the synovitis. These patients are going to the ER because they’re having pain in their hands, and they’re getting told, ‘This is fibromyalgia, go back and see your rheumatologist.’ So it’s something to think about: When you’ve got a patient with active lupus, ultrasound may have a role to play,” according to Dr. Wells.
The big unanswered question is whether early aggressive treatment in SLE patients with these synovial abnormalities – that is, a treat-to-target, ultrasound-guided strategy – can limit erosive changes, avoid disease progression, and improve functional outcomes, as is now known to be the case in RA. Long-term studies will be required to find out, he noted.
Ultrasound of parotid glands in suspected Sjögren’s syndrome is biopsy sparing
Members of the European League Against Rheumatism Ultrasound Primary Sjögren’s Syndrome Study Group recently reported that in a prospective study of 103 consecutive outpatients with clinically suspected primary Sjögren’s syndrome, a positive ultrasound examination of the major salivary glands in combination with the presence of anti-SSA/Ro antibodies was highly predictive of positive parotid and labial gland biopsies. Indeed, a positive ultrasound plus anti-SSA/Ro antibodies showed a high predictive value for Sjögren’s syndrome regardless of whether the classification was based upon American College of Rheumatology, American European Consensus Group, or ACR-EULAR criteria (Ann Rheum Dis. 2017;76[11]:1883-9).
“Ophthalmologists, dentists, and primary care physicians frequently refer patients with dry eyes and dry mouth to us to sort out whether they have Sjögren’s syndrome. The data show now that with a positive salivary gland ultrasound score and a positive anti-SSA/Ro antibody test you can avoid the biopsies,” the rheumatologist said.
That’s a fine thing for patients because these biopsies often result in residual numbness and tingling, he added.
Dr. Wells noted that a multicenter European group recently fine-tuned the criteria for an abnormal salivary gland ultrasound score. They identified echogenicity and homogeneity as the two most reliable items on the score. They also reported that the mean time it took five ultrasonographers to perform salivary gland assessments was reasonable at 11-27 minutes (RMD Open. 2017 Jun 9;3[1]:e000364).
“You can do this essentially in an office visit. The changes in the salivary glands are pathognomonic for Sjögren’s – you won’t get it confused with a neoplasm. I schedule these patients for a 15-minute time slot, and based upon the ultrasound and whether they’re positive or negative for anti-SSA/Ro antibodies I can make some decisions from there,” Dr. Wells explained.
He described what to look for on ultrasound: “A normal parotid looks like a homogeneous gray sponge on ultrasound. In Sjögren’s syndrome, you see icepicklike holes in the sponge. And there’s thickening of the intima, so you see blunting of the arterial wave on pulse wave.”
Implications of ultrasound enthesitis in early spondyloarthritis
French rheumatologists reported on the implications of an ultrasound peripheral enthesis assessment in 402 patients with early axial spondyloarthritis in the French DESIR cohort. The ultrasound evaluation covered the lateral epicondyles, Achilles tendon, and superior and inferior patellar ligament entheses. The results were summed up in ultrasound structural and power Doppler scores. In addition, the investigators obtained spine and sacroiliac joint MRI scans and spine x-rays, all scored centrally.
It turned out that ultrasound abnormalities weren’t useful in monitoring axial spondyloarthritis clinical disease activity as reflected in Bath Ankylosing Spondylitis Disease Activity Index scores, nor were the ultrasound structural and power Doppler scores associated with MRI spine inflammatory lesions or sacroiliitis. However, ultrasound enthesophytes were strongly associated with axial syndesmophytes, suggesting that these ultrasound abnormalities might be a marker of disease severity in axial spondyloarthritis (RMD Open. 2017 Sep 7;3[2]:e000482).
“Whether or not by inhibiting these peripheral enthesophytes you’ll ultimately inhibit further enthesophytes or syndesmophytes from forming is yet to be seen,” Dr. Wells cautioned.
He added, however, that a recent short-term, randomized, placebo-controlled trial in 185 patients with nonradiographic axial spondyloarthritis holds hope in that regard. Investigators in the ongoing multicenter EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic Spondyloarthritis) trial reported that treatment with etanercept was associated with a significantly greater reduction in erosions, an increase in backfill, and improved clinical outcomes, compared with placebo, as assessed by MRIs obtained at baseline and 12 weeks.
The investigators viewed these findings as consistent with an early reparative response to the anti–tumor necrosis factor agent, although they noted that understanding of the biologic agent’s true impact on disease progression awaits longer-term follow-up in the 104-week study (Ann Rheum Dis. 2018 Jan;77[1]:78-84).
Dr. Wells reported serving as a consultant to more than half a dozen pharmaceutical companies and receiving research funding from Abbott, Celgene, and UCB.
EXPERT ANALYSIS FROM RWCS 2018
TNF inhibitors curb spinal x-ray progression in ankylosing spondylitis
MAUI, HAWAII – How long do patients with ankylosing spondylitis need to be on a tumor necrosis factor (TNF) blocker in order to experience clinically meaningful inhibition of spinal x-ray progression?
At least 2 years, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited a study by the rheumatologists of the Swiss Clinical Quality Management Program which he considers one of the recent highlights in rheumatologic imaging.
The mean increase in mSASSS was 0.9 units in 2 years. Prior use of a TNF inhibitor reduced the likelihood of progression by 50% in a multivariate analysis, observed Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is also in private practice in Santa Monica, Calif.
Responders to anti-TNF therapy as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or less at the beginning of a 2-year radiographic interval had a mean mSASSS progression of just 0.31 units in the next 2 years, compared with a 1.45-unit increase in nonresponders to anti-TNF therapy with an ASDAS score above 2.1.
Moreover, patients on anti-TNF therapy who achieved inactive disease status as defined by an ASDAS of 1.3 or less at the beginning of the next 2-year radiographic interval experienced essentially no radiographic progression during that interval, with a mean mSASSS increase of just 0.01 units as compared with a 0.52-unit increase in those with an ASDAS of 1.3-2.1. The inference, according to the investigators, is that the reduction in spinal x-ray progression associated with TNF inhibitor (TNFi) therapy was mediated by the biologic therapy’s inhibitory effect on disease activity.
“We present important clues concerning the period of time needed before the inhibitory effects can be objectified: around 2 years of continuous TNFi use, as there was no impact of TNFi treatment during a 2-year radiographic interval, while there was an effect if the treatment was started before this interval. ... Our study suggests that [an ASDAS of 1.3 or less] might be an adequate target, if the goal of treatment is inhibition of further spinal radiographic damage in addition to control of signs and symptoms, ” according to the investigators (Ann Rheum Dis. 2018 Jan;77[1]:63-9).
Dr. Troum reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.
MAUI, HAWAII – How long do patients with ankylosing spondylitis need to be on a tumor necrosis factor (TNF) blocker in order to experience clinically meaningful inhibition of spinal x-ray progression?
At least 2 years, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited a study by the rheumatologists of the Swiss Clinical Quality Management Program which he considers one of the recent highlights in rheumatologic imaging.
The mean increase in mSASSS was 0.9 units in 2 years. Prior use of a TNF inhibitor reduced the likelihood of progression by 50% in a multivariate analysis, observed Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is also in private practice in Santa Monica, Calif.
Responders to anti-TNF therapy as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or less at the beginning of a 2-year radiographic interval had a mean mSASSS progression of just 0.31 units in the next 2 years, compared with a 1.45-unit increase in nonresponders to anti-TNF therapy with an ASDAS score above 2.1.
Moreover, patients on anti-TNF therapy who achieved inactive disease status as defined by an ASDAS of 1.3 or less at the beginning of the next 2-year radiographic interval experienced essentially no radiographic progression during that interval, with a mean mSASSS increase of just 0.01 units as compared with a 0.52-unit increase in those with an ASDAS of 1.3-2.1. The inference, according to the investigators, is that the reduction in spinal x-ray progression associated with TNF inhibitor (TNFi) therapy was mediated by the biologic therapy’s inhibitory effect on disease activity.
“We present important clues concerning the period of time needed before the inhibitory effects can be objectified: around 2 years of continuous TNFi use, as there was no impact of TNFi treatment during a 2-year radiographic interval, while there was an effect if the treatment was started before this interval. ... Our study suggests that [an ASDAS of 1.3 or less] might be an adequate target, if the goal of treatment is inhibition of further spinal radiographic damage in addition to control of signs and symptoms, ” according to the investigators (Ann Rheum Dis. 2018 Jan;77[1]:63-9).
Dr. Troum reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.
MAUI, HAWAII – How long do patients with ankylosing spondylitis need to be on a tumor necrosis factor (TNF) blocker in order to experience clinically meaningful inhibition of spinal x-ray progression?
At least 2 years, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited a study by the rheumatologists of the Swiss Clinical Quality Management Program which he considers one of the recent highlights in rheumatologic imaging.
The mean increase in mSASSS was 0.9 units in 2 years. Prior use of a TNF inhibitor reduced the likelihood of progression by 50% in a multivariate analysis, observed Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is also in private practice in Santa Monica, Calif.
Responders to anti-TNF therapy as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or less at the beginning of a 2-year radiographic interval had a mean mSASSS progression of just 0.31 units in the next 2 years, compared with a 1.45-unit increase in nonresponders to anti-TNF therapy with an ASDAS score above 2.1.
Moreover, patients on anti-TNF therapy who achieved inactive disease status as defined by an ASDAS of 1.3 or less at the beginning of the next 2-year radiographic interval experienced essentially no radiographic progression during that interval, with a mean mSASSS increase of just 0.01 units as compared with a 0.52-unit increase in those with an ASDAS of 1.3-2.1. The inference, according to the investigators, is that the reduction in spinal x-ray progression associated with TNF inhibitor (TNFi) therapy was mediated by the biologic therapy’s inhibitory effect on disease activity.
“We present important clues concerning the period of time needed before the inhibitory effects can be objectified: around 2 years of continuous TNFi use, as there was no impact of TNFi treatment during a 2-year radiographic interval, while there was an effect if the treatment was started before this interval. ... Our study suggests that [an ASDAS of 1.3 or less] might be an adequate target, if the goal of treatment is inhibition of further spinal radiographic damage in addition to control of signs and symptoms, ” according to the investigators (Ann Rheum Dis. 2018 Jan;77[1]:63-9).
Dr. Troum reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2018
Badly behaved neutrophils are novel target in rheumatic diseases
MAUI, HAWAII – For most of her career as a pediatric rheumatologist and immunologist, Anne M. Stevens, MD, PhD, didn’t find neutrophils terribly interesting.
“I’m more of a T-cell person. T cells are very precise, they’re regulated, they’re very sophisticated cells. Neutrophils are like these bumbling idiots that just come in and hit everything in sight and cause all sorts of damage,” she observed at the 2018 Rheumatology Winter Clinical Symposium.
Recently, however, she’s changed her mind. Research in the past few years demonstrates that there’s a lot more to neutrophils than previously known. Neutrophils are not only the first-responder immune cells to acutely inflamed tissue, as has long been recognized, but they also play a huge role in initiating and perpetuating chronic inflammation. Indeed, neutrophils figure prominently in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus (SLE), antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, and perhaps in major nonautoimmune diseases as well, including atherosclerosis, type 1 diabetes, thrombosis, and some forms of kidney disease, explained Dr. Stevens, chief of pediatric rheumatology at the University of Washington, Seattle.
Indeed, it’s now clear that neutrophils can either die quietly or become activated in death by creating neutrophil extracellular traps, or NETs, in a process called NETosis. Even though the activated neutrophil is dead, its exteriorized NETs continue to function, grabbing and killing bacterial pathogens. But the NETs also attract immune cells. These NETs are long strands of sticky DNA containing chromatin, histones, elastase, myeloperoxidase, hypercitrullinated proteins, and other autoantigens. NETosis exposes these autoantigens to the immune system, with resultant generation of autoimmune responses in predisposed individuals.
Much detail has been learned about this process. For example, one type of neutrophil death results from lymphokine-activated killer cells releasing perforin, which pokes holes in the neutrophil cell membrane, allowing an influx of calcium. The inflow of calcium triggers activation of peptidyl arginine deiminases, and these enzymes in turn cause hypercitrullination of autoantigens, leading to formation of anti–citrullinated peptide autoantibodies (ACPAs). These ACPAs cause inflammation by inducing complement activation and binding to Fc gamma receptors on phagocytes.
Investigators at the Systemic Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and several other research centers have shown that mixing RA synovial fibroblasts with NETs induces production of interleukin-6 and ACPAs. In a mouse model of RA, this leads to cartilage loss in joints, providing a plausible mechanistic explanation for joint damage in RA (Sci Immunol. 2017 Apr;2[10]:eaag3358).
Potential therapeutic strategies targeting NETosis
The various treatment approaches under study aim to either inhibit NET release, curb recruitment of neutrophils for activation, promote migration of neutrophils away from sites of inflammation, or foster efferocytosis.
Among the therapeutic possibilities are calcineurin inhibitors as a means of preventing the influx of calcium into neutrophils, peptidyl arginine deiminase inhibitors such as Cl-amidine to prevent hypercitrullination, complement component 5a-receptor antagonists to decrease NET formation, the myeloperoxidase inhibitor known for now as PF-1355, and N-acetyl cysteine to scavenge proinflammatory reactive oxygen species and thereby reduce NET release.
The key will be to develop highly selective agents that encourage well-behaved neutrophils; across-the-board blockade of neutrophil activity would be terribly immunosuppressive and likely dangerous.
“What if we could block neutrophil recruitment just to the organ we’re worried about? If I’m worried about nephritis, let’s just block neutrophil infiltration into the kidneys. There are drugs being developed that will block the specific types of integrins involved,” Dr. Stevens said.
She reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – For most of her career as a pediatric rheumatologist and immunologist, Anne M. Stevens, MD, PhD, didn’t find neutrophils terribly interesting.
“I’m more of a T-cell person. T cells are very precise, they’re regulated, they’re very sophisticated cells. Neutrophils are like these bumbling idiots that just come in and hit everything in sight and cause all sorts of damage,” she observed at the 2018 Rheumatology Winter Clinical Symposium.
Recently, however, she’s changed her mind. Research in the past few years demonstrates that there’s a lot more to neutrophils than previously known. Neutrophils are not only the first-responder immune cells to acutely inflamed tissue, as has long been recognized, but they also play a huge role in initiating and perpetuating chronic inflammation. Indeed, neutrophils figure prominently in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus (SLE), antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, and perhaps in major nonautoimmune diseases as well, including atherosclerosis, type 1 diabetes, thrombosis, and some forms of kidney disease, explained Dr. Stevens, chief of pediatric rheumatology at the University of Washington, Seattle.
Indeed, it’s now clear that neutrophils can either die quietly or become activated in death by creating neutrophil extracellular traps, or NETs, in a process called NETosis. Even though the activated neutrophil is dead, its exteriorized NETs continue to function, grabbing and killing bacterial pathogens. But the NETs also attract immune cells. These NETs are long strands of sticky DNA containing chromatin, histones, elastase, myeloperoxidase, hypercitrullinated proteins, and other autoantigens. NETosis exposes these autoantigens to the immune system, with resultant generation of autoimmune responses in predisposed individuals.
Much detail has been learned about this process. For example, one type of neutrophil death results from lymphokine-activated killer cells releasing perforin, which pokes holes in the neutrophil cell membrane, allowing an influx of calcium. The inflow of calcium triggers activation of peptidyl arginine deiminases, and these enzymes in turn cause hypercitrullination of autoantigens, leading to formation of anti–citrullinated peptide autoantibodies (ACPAs). These ACPAs cause inflammation by inducing complement activation and binding to Fc gamma receptors on phagocytes.
Investigators at the Systemic Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and several other research centers have shown that mixing RA synovial fibroblasts with NETs induces production of interleukin-6 and ACPAs. In a mouse model of RA, this leads to cartilage loss in joints, providing a plausible mechanistic explanation for joint damage in RA (Sci Immunol. 2017 Apr;2[10]:eaag3358).
Potential therapeutic strategies targeting NETosis
The various treatment approaches under study aim to either inhibit NET release, curb recruitment of neutrophils for activation, promote migration of neutrophils away from sites of inflammation, or foster efferocytosis.
Among the therapeutic possibilities are calcineurin inhibitors as a means of preventing the influx of calcium into neutrophils, peptidyl arginine deiminase inhibitors such as Cl-amidine to prevent hypercitrullination, complement component 5a-receptor antagonists to decrease NET formation, the myeloperoxidase inhibitor known for now as PF-1355, and N-acetyl cysteine to scavenge proinflammatory reactive oxygen species and thereby reduce NET release.
The key will be to develop highly selective agents that encourage well-behaved neutrophils; across-the-board blockade of neutrophil activity would be terribly immunosuppressive and likely dangerous.
“What if we could block neutrophil recruitment just to the organ we’re worried about? If I’m worried about nephritis, let’s just block neutrophil infiltration into the kidneys. There are drugs being developed that will block the specific types of integrins involved,” Dr. Stevens said.
She reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – For most of her career as a pediatric rheumatologist and immunologist, Anne M. Stevens, MD, PhD, didn’t find neutrophils terribly interesting.
“I’m more of a T-cell person. T cells are very precise, they’re regulated, they’re very sophisticated cells. Neutrophils are like these bumbling idiots that just come in and hit everything in sight and cause all sorts of damage,” she observed at the 2018 Rheumatology Winter Clinical Symposium.
Recently, however, she’s changed her mind. Research in the past few years demonstrates that there’s a lot more to neutrophils than previously known. Neutrophils are not only the first-responder immune cells to acutely inflamed tissue, as has long been recognized, but they also play a huge role in initiating and perpetuating chronic inflammation. Indeed, neutrophils figure prominently in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus (SLE), antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, and perhaps in major nonautoimmune diseases as well, including atherosclerosis, type 1 diabetes, thrombosis, and some forms of kidney disease, explained Dr. Stevens, chief of pediatric rheumatology at the University of Washington, Seattle.
Indeed, it’s now clear that neutrophils can either die quietly or become activated in death by creating neutrophil extracellular traps, or NETs, in a process called NETosis. Even though the activated neutrophil is dead, its exteriorized NETs continue to function, grabbing and killing bacterial pathogens. But the NETs also attract immune cells. These NETs are long strands of sticky DNA containing chromatin, histones, elastase, myeloperoxidase, hypercitrullinated proteins, and other autoantigens. NETosis exposes these autoantigens to the immune system, with resultant generation of autoimmune responses in predisposed individuals.
Much detail has been learned about this process. For example, one type of neutrophil death results from lymphokine-activated killer cells releasing perforin, which pokes holes in the neutrophil cell membrane, allowing an influx of calcium. The inflow of calcium triggers activation of peptidyl arginine deiminases, and these enzymes in turn cause hypercitrullination of autoantigens, leading to formation of anti–citrullinated peptide autoantibodies (ACPAs). These ACPAs cause inflammation by inducing complement activation and binding to Fc gamma receptors on phagocytes.
Investigators at the Systemic Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and several other research centers have shown that mixing RA synovial fibroblasts with NETs induces production of interleukin-6 and ACPAs. In a mouse model of RA, this leads to cartilage loss in joints, providing a plausible mechanistic explanation for joint damage in RA (Sci Immunol. 2017 Apr;2[10]:eaag3358).
Potential therapeutic strategies targeting NETosis
The various treatment approaches under study aim to either inhibit NET release, curb recruitment of neutrophils for activation, promote migration of neutrophils away from sites of inflammation, or foster efferocytosis.
Among the therapeutic possibilities are calcineurin inhibitors as a means of preventing the influx of calcium into neutrophils, peptidyl arginine deiminase inhibitors such as Cl-amidine to prevent hypercitrullination, complement component 5a-receptor antagonists to decrease NET formation, the myeloperoxidase inhibitor known for now as PF-1355, and N-acetyl cysteine to scavenge proinflammatory reactive oxygen species and thereby reduce NET release.
The key will be to develop highly selective agents that encourage well-behaved neutrophils; across-the-board blockade of neutrophil activity would be terribly immunosuppressive and likely dangerous.
“What if we could block neutrophil recruitment just to the organ we’re worried about? If I’m worried about nephritis, let’s just block neutrophil infiltration into the kidneys. There are drugs being developed that will block the specific types of integrins involved,” Dr. Stevens said.
She reported having no financial conflicts regarding her presentation.
EXPERT ANALYSIS FROM RWCS 2018