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Immunogenicity concerns for biosimilars so far don’t go beyond originator biologics
A key factor that impacts the efficacy and the toxicity of biologics used for rheumatic diseases is their immunogenicity, and this factor doesn’t appear to be any different for biosimilars in studies conducted so far.
In a meta-analysis of 63 studies of tumor necrosis factor (TNF) inhibitors, investigators including Daniel E. Furst, MD, professor of rheumatology at the University of Washington, Seattle, who also is affiliated with the University of California, Los Angeles, and the University of Florence, Italy, found that antidrug antibodies developed in 17% of patients (BioDrugs 2015;29:241-58).
“That doesn’t sound too bad, but does it differ by medication?” asked Dr. Furst, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “For infliximab, 30% of the time, there are antidrug antibodies. So if that has a clinical effect, that’s a big deal. For certolizumab ... it’s only 6%, so there is a huge difference within the TNF inhibitors.” At the same time, antidrug antibodies developed in patients on adalimumab 23% of the time, followed by certolizumab (6%), golimumab (4%), and etanercept (2%).
One approach to circumventing the impact of antidrug antibodies on clinical response is by using immunosuppression, which in the meta-analysis had a 70% probability for decreasing antidrug antibodies. But this approach comes with a hitch, Dr. Furst said. The effect of immunosuppression on antidrug antibody positivity differs by disease. Immunosuppression had a 78% probability for decreasing antidrug antibody positivity in RA, 63% probability in inflammatory bowel disease, and 32% probability in ankylosing spondylitis. “That’s a wild mix of immunogenicity and the possibility that it’s going to affect the underlying response,” he said. The best studies in this area are of infliximab and adalimumab, which showed that antidrug antibodies in patients on infliximab reduced the probability of a clinical response by 54% and for adalimumab by 65%.
The same meta-analysis found that there were more antibodies to adalimumab than to certolizumab, golimumab, or etanercept, and also more antibodies to infliximab than to certolizumab, golimumab, or etanercept, but no difference between adalimumab and infliximab. “You’d think that maybe there is a difference between adalimumab and infliximab, but that’s not true,” Dr. Furst said. The apparent effect on the percentage of antidrug antibodies depends on what type of assay is used. For example, radioimmunoassay measures about 11% more antidrug antibodies, compared with enzyme-linked immunosorbent assay. Disease duration also matters. Each year of disease duration increases the antidrug antibodies by 1%.
What about the non-TNF inhibitors? A meta-analysis of five core trials of tocilizumab for RA found that the antidrug antibodies ranged from 1.7% at baseline to 2.3% during the respective trials (Clin Ther. 2010;32:1597-1609). “Anywhere along the way, the percentage of antidrug antibodies was about 1.5%,” said Dr. Furst, who was not involved with the study. “So as opposed to the TNF inhibitors, when you look at tocilizumab, this whole immunity question is probably a non-issue. The same is true for abatacept. With rituximab, the question is a little bit different. In one randomized, controlled trial, immunogenicity was 2.9%, while in the next it was 7.9%. In an open-label trial, it was 11.5%. So I think for rituximab we have to assume that you have some potentially important antidrug antibodies that might affect response.”
Studies have shown that antidrug antibodies do affect the pharmacokinetics of a biologic (and thereby clinical response) by producing lower trough levels of the biologic through an increase in its clearance. However, studies of infliximab and its biosimilars have not yielded any significant differences in clinical responses rates despite small differences in rates of antidrug antibodies or in rates of treatment-emergent adverse events, he said.
There has also been no difference in disease worsening in the only reported double-blind, randomized, switching study for infliximab and an infliximab biosimilar, the NOR-SWITCH study. However, the small numbers of patients in the study with certain diseases for which infliximab is indicated do not allow for conclusions to be drawn for specific diseases, Dr. Furst said.
Dr. Furst disclosed that he has received grant/research support from AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, and Roche/Genentech. He is also a consultant for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Novartis, Pfizer, and Roche/Genentech. Global Academy for Medical Education and this news organization are owned by the same parent company.
A key factor that impacts the efficacy and the toxicity of biologics used for rheumatic diseases is their immunogenicity, and this factor doesn’t appear to be any different for biosimilars in studies conducted so far.
In a meta-analysis of 63 studies of tumor necrosis factor (TNF) inhibitors, investigators including Daniel E. Furst, MD, professor of rheumatology at the University of Washington, Seattle, who also is affiliated with the University of California, Los Angeles, and the University of Florence, Italy, found that antidrug antibodies developed in 17% of patients (BioDrugs 2015;29:241-58).
“That doesn’t sound too bad, but does it differ by medication?” asked Dr. Furst, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “For infliximab, 30% of the time, there are antidrug antibodies. So if that has a clinical effect, that’s a big deal. For certolizumab ... it’s only 6%, so there is a huge difference within the TNF inhibitors.” At the same time, antidrug antibodies developed in patients on adalimumab 23% of the time, followed by certolizumab (6%), golimumab (4%), and etanercept (2%).
One approach to circumventing the impact of antidrug antibodies on clinical response is by using immunosuppression, which in the meta-analysis had a 70% probability for decreasing antidrug antibodies. But this approach comes with a hitch, Dr. Furst said. The effect of immunosuppression on antidrug antibody positivity differs by disease. Immunosuppression had a 78% probability for decreasing antidrug antibody positivity in RA, 63% probability in inflammatory bowel disease, and 32% probability in ankylosing spondylitis. “That’s a wild mix of immunogenicity and the possibility that it’s going to affect the underlying response,” he said. The best studies in this area are of infliximab and adalimumab, which showed that antidrug antibodies in patients on infliximab reduced the probability of a clinical response by 54% and for adalimumab by 65%.
The same meta-analysis found that there were more antibodies to adalimumab than to certolizumab, golimumab, or etanercept, and also more antibodies to infliximab than to certolizumab, golimumab, or etanercept, but no difference between adalimumab and infliximab. “You’d think that maybe there is a difference between adalimumab and infliximab, but that’s not true,” Dr. Furst said. The apparent effect on the percentage of antidrug antibodies depends on what type of assay is used. For example, radioimmunoassay measures about 11% more antidrug antibodies, compared with enzyme-linked immunosorbent assay. Disease duration also matters. Each year of disease duration increases the antidrug antibodies by 1%.
What about the non-TNF inhibitors? A meta-analysis of five core trials of tocilizumab for RA found that the antidrug antibodies ranged from 1.7% at baseline to 2.3% during the respective trials (Clin Ther. 2010;32:1597-1609). “Anywhere along the way, the percentage of antidrug antibodies was about 1.5%,” said Dr. Furst, who was not involved with the study. “So as opposed to the TNF inhibitors, when you look at tocilizumab, this whole immunity question is probably a non-issue. The same is true for abatacept. With rituximab, the question is a little bit different. In one randomized, controlled trial, immunogenicity was 2.9%, while in the next it was 7.9%. In an open-label trial, it was 11.5%. So I think for rituximab we have to assume that you have some potentially important antidrug antibodies that might affect response.”
Studies have shown that antidrug antibodies do affect the pharmacokinetics of a biologic (and thereby clinical response) by producing lower trough levels of the biologic through an increase in its clearance. However, studies of infliximab and its biosimilars have not yielded any significant differences in clinical responses rates despite small differences in rates of antidrug antibodies or in rates of treatment-emergent adverse events, he said.
There has also been no difference in disease worsening in the only reported double-blind, randomized, switching study for infliximab and an infliximab biosimilar, the NOR-SWITCH study. However, the small numbers of patients in the study with certain diseases for which infliximab is indicated do not allow for conclusions to be drawn for specific diseases, Dr. Furst said.
Dr. Furst disclosed that he has received grant/research support from AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, and Roche/Genentech. He is also a consultant for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Novartis, Pfizer, and Roche/Genentech. Global Academy for Medical Education and this news organization are owned by the same parent company.
A key factor that impacts the efficacy and the toxicity of biologics used for rheumatic diseases is their immunogenicity, and this factor doesn’t appear to be any different for biosimilars in studies conducted so far.
In a meta-analysis of 63 studies of tumor necrosis factor (TNF) inhibitors, investigators including Daniel E. Furst, MD, professor of rheumatology at the University of Washington, Seattle, who also is affiliated with the University of California, Los Angeles, and the University of Florence, Italy, found that antidrug antibodies developed in 17% of patients (BioDrugs 2015;29:241-58).
“That doesn’t sound too bad, but does it differ by medication?” asked Dr. Furst, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “For infliximab, 30% of the time, there are antidrug antibodies. So if that has a clinical effect, that’s a big deal. For certolizumab ... it’s only 6%, so there is a huge difference within the TNF inhibitors.” At the same time, antidrug antibodies developed in patients on adalimumab 23% of the time, followed by certolizumab (6%), golimumab (4%), and etanercept (2%).
One approach to circumventing the impact of antidrug antibodies on clinical response is by using immunosuppression, which in the meta-analysis had a 70% probability for decreasing antidrug antibodies. But this approach comes with a hitch, Dr. Furst said. The effect of immunosuppression on antidrug antibody positivity differs by disease. Immunosuppression had a 78% probability for decreasing antidrug antibody positivity in RA, 63% probability in inflammatory bowel disease, and 32% probability in ankylosing spondylitis. “That’s a wild mix of immunogenicity and the possibility that it’s going to affect the underlying response,” he said. The best studies in this area are of infliximab and adalimumab, which showed that antidrug antibodies in patients on infliximab reduced the probability of a clinical response by 54% and for adalimumab by 65%.
The same meta-analysis found that there were more antibodies to adalimumab than to certolizumab, golimumab, or etanercept, and also more antibodies to infliximab than to certolizumab, golimumab, or etanercept, but no difference between adalimumab and infliximab. “You’d think that maybe there is a difference between adalimumab and infliximab, but that’s not true,” Dr. Furst said. The apparent effect on the percentage of antidrug antibodies depends on what type of assay is used. For example, radioimmunoassay measures about 11% more antidrug antibodies, compared with enzyme-linked immunosorbent assay. Disease duration also matters. Each year of disease duration increases the antidrug antibodies by 1%.
What about the non-TNF inhibitors? A meta-analysis of five core trials of tocilizumab for RA found that the antidrug antibodies ranged from 1.7% at baseline to 2.3% during the respective trials (Clin Ther. 2010;32:1597-1609). “Anywhere along the way, the percentage of antidrug antibodies was about 1.5%,” said Dr. Furst, who was not involved with the study. “So as opposed to the TNF inhibitors, when you look at tocilizumab, this whole immunity question is probably a non-issue. The same is true for abatacept. With rituximab, the question is a little bit different. In one randomized, controlled trial, immunogenicity was 2.9%, while in the next it was 7.9%. In an open-label trial, it was 11.5%. So I think for rituximab we have to assume that you have some potentially important antidrug antibodies that might affect response.”
Studies have shown that antidrug antibodies do affect the pharmacokinetics of a biologic (and thereby clinical response) by producing lower trough levels of the biologic through an increase in its clearance. However, studies of infliximab and its biosimilars have not yielded any significant differences in clinical responses rates despite small differences in rates of antidrug antibodies or in rates of treatment-emergent adverse events, he said.
There has also been no difference in disease worsening in the only reported double-blind, randomized, switching study for infliximab and an infliximab biosimilar, the NOR-SWITCH study. However, the small numbers of patients in the study with certain diseases for which infliximab is indicated do not allow for conclusions to be drawn for specific diseases, Dr. Furst said.
Dr. Furst disclosed that he has received grant/research support from AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, and Roche/Genentech. He is also a consultant for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Novartis, Pfizer, and Roche/Genentech. Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM THE ANNUAL PERSPECTIVES IN RHEUMATIC DISEASES
Early ankylosing spondylitis treatment stops transition from inflammatory to bone-forming fatty lesions
Structural damage in axial and peripheral ankylosing spondylitis is the result of a combination of destruction and new bone formation, which can be halted if treated early and for long enough, according to Dirk Elewaut, MD, PhD.
“There is a longstanding paradox in the field of ankylosing spondylitis, as to whether there is a strict relationship between the inflammation that leads to the signs and symptoms in patients, and the structural progression,” said Dr. Elewaut, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “ ”
One key reason why the early TNF inhibition trials showed no effect of treatment on structural progression stemmed from inadequate study design. “The original studies were underpowered, and the patients used NSAIDs,” he said. “We also know that the anti-inflammatory effect [of TNF inhibition] is not 100%. So you have a clear drop in inflammation with biologics, but it’s not completely stopped. This led to a lot of speculation as to whether inflammation and ankyloses are coupled or not.”
More recently, researchers have honed in on the transition from acute inflammatory lesions visible on MRI by bone marrow edema to so-called fatty lesions, which are also visible on MRI. They have observed that fatty lesions are associated with new bone formation. “Lesions containing more fat are thought to be more difficult to modulate by biological therapy,” Dr. Elewaut said. “Once you have a fatty lesion, you have some kind of metabolic disease of the bone, and it’s a one-way road to the development of new syndesmophytes. So in other words, it is essential to assess the relationship between inflammation and new bone formation with both the STIR [short tau inversion recovery images] and T1-weighted MRI.”
A working hypothesis among AS researchers is that the effect of anti-TNF therapy on radiologic progression depends on the relative number of acute and mature inflammatory lesions that individual patients have. “Early diagnosis is a prerequisite for advances in disease modification,” he said. At least three “windows of opportunity” for disease modification exist, Dr. Elewaut continued. One is that the link between inflammation as measured by clinical parameters and new bone formation will be more evident in early AS. The second is that early treatment of patients with axial AS and spinal inflammation with anti-TNF agents will prevent new bone formation. The third is that reduction of new bone formation in established AS will be observed only with long-term anti-TNF therapy after mature lesions have resolved/repaired, and no new inflammatory lesions are being formed. One study found that patients with a delay of more than 10 years starting anti-TNF therapy were more likely to progress, compared with patients who received therapy earlier (odds ratio, 2.4; P = .03; see Arthritis Rheum. 2013;65:645-54). “The message here is quite clear,” Dr. Elewaut said. “The earlier we treat intensively, the better impact you have on structural outcomes.”
In a trial known as CRESPA (Clinical Remission in peripheral SPondyloArthritis), researchers including Dr. Elewaut evaluated the efficacy and safety of golimumab (Simponi) to induce clinical remission in patients with early, active peripheral AS (Ann Rheum Dis. 2017;76:1389-95). In all, 60 patients were randomized to golimumab or placebo for 24 weeks. At week 24, a significantly higher percentage of patients receiving golimumab achieved clinical remission, compared with placebo (75% vs. 20%, respectively; P less than .001). At week 12, similar results were observed (70% vs. 15%; P less than .001).
“These were very striking results in this early disease population,” Dr. Elewaut said. In a follow-up analysis, the researchers withdrew therapy in patients who reached clinical remission, to see what would happen. “At 1.5 years of follow-up, 57% of patients are in drug-free remission,” Dr. Elewaut said. “This is interesting and suggests that at least in a fraction of those patients, you can actually achieve a drug-free remission.” Predictors for relapse included pre-existing psoriasis and having more than five swollen joints.
Dr. Elewaut disclosed that he is a member of the speakers bureau for AbbVie, Novartis, Pfizer, and UCB. Global Academy for Medical Education and this news organization are owned by the same parent company.
Structural damage in axial and peripheral ankylosing spondylitis is the result of a combination of destruction and new bone formation, which can be halted if treated early and for long enough, according to Dirk Elewaut, MD, PhD.
“There is a longstanding paradox in the field of ankylosing spondylitis, as to whether there is a strict relationship between the inflammation that leads to the signs and symptoms in patients, and the structural progression,” said Dr. Elewaut, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “ ”
One key reason why the early TNF inhibition trials showed no effect of treatment on structural progression stemmed from inadequate study design. “The original studies were underpowered, and the patients used NSAIDs,” he said. “We also know that the anti-inflammatory effect [of TNF inhibition] is not 100%. So you have a clear drop in inflammation with biologics, but it’s not completely stopped. This led to a lot of speculation as to whether inflammation and ankyloses are coupled or not.”
More recently, researchers have honed in on the transition from acute inflammatory lesions visible on MRI by bone marrow edema to so-called fatty lesions, which are also visible on MRI. They have observed that fatty lesions are associated with new bone formation. “Lesions containing more fat are thought to be more difficult to modulate by biological therapy,” Dr. Elewaut said. “Once you have a fatty lesion, you have some kind of metabolic disease of the bone, and it’s a one-way road to the development of new syndesmophytes. So in other words, it is essential to assess the relationship between inflammation and new bone formation with both the STIR [short tau inversion recovery images] and T1-weighted MRI.”
A working hypothesis among AS researchers is that the effect of anti-TNF therapy on radiologic progression depends on the relative number of acute and mature inflammatory lesions that individual patients have. “Early diagnosis is a prerequisite for advances in disease modification,” he said. At least three “windows of opportunity” for disease modification exist, Dr. Elewaut continued. One is that the link between inflammation as measured by clinical parameters and new bone formation will be more evident in early AS. The second is that early treatment of patients with axial AS and spinal inflammation with anti-TNF agents will prevent new bone formation. The third is that reduction of new bone formation in established AS will be observed only with long-term anti-TNF therapy after mature lesions have resolved/repaired, and no new inflammatory lesions are being formed. One study found that patients with a delay of more than 10 years starting anti-TNF therapy were more likely to progress, compared with patients who received therapy earlier (odds ratio, 2.4; P = .03; see Arthritis Rheum. 2013;65:645-54). “The message here is quite clear,” Dr. Elewaut said. “The earlier we treat intensively, the better impact you have on structural outcomes.”
In a trial known as CRESPA (Clinical Remission in peripheral SPondyloArthritis), researchers including Dr. Elewaut evaluated the efficacy and safety of golimumab (Simponi) to induce clinical remission in patients with early, active peripheral AS (Ann Rheum Dis. 2017;76:1389-95). In all, 60 patients were randomized to golimumab or placebo for 24 weeks. At week 24, a significantly higher percentage of patients receiving golimumab achieved clinical remission, compared with placebo (75% vs. 20%, respectively; P less than .001). At week 12, similar results were observed (70% vs. 15%; P less than .001).
“These were very striking results in this early disease population,” Dr. Elewaut said. In a follow-up analysis, the researchers withdrew therapy in patients who reached clinical remission, to see what would happen. “At 1.5 years of follow-up, 57% of patients are in drug-free remission,” Dr. Elewaut said. “This is interesting and suggests that at least in a fraction of those patients, you can actually achieve a drug-free remission.” Predictors for relapse included pre-existing psoriasis and having more than five swollen joints.
Dr. Elewaut disclosed that he is a member of the speakers bureau for AbbVie, Novartis, Pfizer, and UCB. Global Academy for Medical Education and this news organization are owned by the same parent company.
Structural damage in axial and peripheral ankylosing spondylitis is the result of a combination of destruction and new bone formation, which can be halted if treated early and for long enough, according to Dirk Elewaut, MD, PhD.
“There is a longstanding paradox in the field of ankylosing spondylitis, as to whether there is a strict relationship between the inflammation that leads to the signs and symptoms in patients, and the structural progression,” said Dr. Elewaut, who spoke at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “ ”
One key reason why the early TNF inhibition trials showed no effect of treatment on structural progression stemmed from inadequate study design. “The original studies were underpowered, and the patients used NSAIDs,” he said. “We also know that the anti-inflammatory effect [of TNF inhibition] is not 100%. So you have a clear drop in inflammation with biologics, but it’s not completely stopped. This led to a lot of speculation as to whether inflammation and ankyloses are coupled or not.”
More recently, researchers have honed in on the transition from acute inflammatory lesions visible on MRI by bone marrow edema to so-called fatty lesions, which are also visible on MRI. They have observed that fatty lesions are associated with new bone formation. “Lesions containing more fat are thought to be more difficult to modulate by biological therapy,” Dr. Elewaut said. “Once you have a fatty lesion, you have some kind of metabolic disease of the bone, and it’s a one-way road to the development of new syndesmophytes. So in other words, it is essential to assess the relationship between inflammation and new bone formation with both the STIR [short tau inversion recovery images] and T1-weighted MRI.”
A working hypothesis among AS researchers is that the effect of anti-TNF therapy on radiologic progression depends on the relative number of acute and mature inflammatory lesions that individual patients have. “Early diagnosis is a prerequisite for advances in disease modification,” he said. At least three “windows of opportunity” for disease modification exist, Dr. Elewaut continued. One is that the link between inflammation as measured by clinical parameters and new bone formation will be more evident in early AS. The second is that early treatment of patients with axial AS and spinal inflammation with anti-TNF agents will prevent new bone formation. The third is that reduction of new bone formation in established AS will be observed only with long-term anti-TNF therapy after mature lesions have resolved/repaired, and no new inflammatory lesions are being formed. One study found that patients with a delay of more than 10 years starting anti-TNF therapy were more likely to progress, compared with patients who received therapy earlier (odds ratio, 2.4; P = .03; see Arthritis Rheum. 2013;65:645-54). “The message here is quite clear,” Dr. Elewaut said. “The earlier we treat intensively, the better impact you have on structural outcomes.”
In a trial known as CRESPA (Clinical Remission in peripheral SPondyloArthritis), researchers including Dr. Elewaut evaluated the efficacy and safety of golimumab (Simponi) to induce clinical remission in patients with early, active peripheral AS (Ann Rheum Dis. 2017;76:1389-95). In all, 60 patients were randomized to golimumab or placebo for 24 weeks. At week 24, a significantly higher percentage of patients receiving golimumab achieved clinical remission, compared with placebo (75% vs. 20%, respectively; P less than .001). At week 12, similar results were observed (70% vs. 15%; P less than .001).
“These were very striking results in this early disease population,” Dr. Elewaut said. In a follow-up analysis, the researchers withdrew therapy in patients who reached clinical remission, to see what would happen. “At 1.5 years of follow-up, 57% of patients are in drug-free remission,” Dr. Elewaut said. “This is interesting and suggests that at least in a fraction of those patients, you can actually achieve a drug-free remission.” Predictors for relapse included pre-existing psoriasis and having more than five swollen joints.
Dr. Elewaut disclosed that he is a member of the speakers bureau for AbbVie, Novartis, Pfizer, and UCB. Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM ANNUAL PERSPECTIVES IN RHEUMATIC DISEASES
‘Multimorbidities’ in RA make impact on treatment efficacy, disease activity
While clinicians are accustomed to managing patients with rheumatoid arthritis and comorbidities, RA patients more frequently have “multimorbidities” – the simultaneous presence of two or more chronic conditions.
“For anyone who sees patients, this is the reality of our lives,” said Jeffrey R. Curtis, MD, at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. Some conditions are “bystanders” that don’t impact RA, some are risk factors for RA, and some can be caused by RA treatments, said Dr. Curtis, professor of medicine and William J. Koopman Professor in Rheumatology and Immunology at the University of Alabama at Birmingham. He discussed several comorbid conditions and their interactions with RA.
Obesity’s toll on disease activity
It’s long been recognized that obesity along with RA makes things worse for patients, he said: “If you have a patient who is obese, with a BMI [body mass index] over 30-35, they’re less likely clinically to achieve low disease activity or remission.”
Obesity also affects biomarkers, he said. The multibiomarker disease activity test, marketed as Vectra DA, incorporates several adipokines in its score, but given any level of RA disease, that score is roughly 5 units higher if someone is obese (Sem Arthritis Rheum. 2017 Aug 2. doi: 10.1016/j.semarthrit.2017.07.010). “The company that manufactures the test is working on an adjustment factor to optimize the role of obesity and what those adipokines are doing to better predict x-ray progression to take this influence into account,” he said. “How we measure obesity and how we’re measuring RA are probably very much affected by this issue.”
RA and the somatization comorbidity phenotype
A second common co-occurrence is what Dr. Curtis calls a somatization comorbidity phenotype (SCP), defined as RA with several other ailments such as fibromyalgia, depression, anxiety, sleep apnea, or neuropathy. “The troubling thing about this is I could cure this patient’s RA tomorrow, but they actually wouldn’t feel better in their overall health because of other things dragging down their function,” he said, noting patients are more concerned about their fatigue and pain than their swollen joint count or DAS28 score.
Dr. Curtis and his colleagues completed a recent analysis that’s in press in Arthritis Research & Therapy of about 800 RA patients in the United States starting certolizumab pegol (Cimzia) to look for how well patients with this phenotype responded to a tumor necrosis factor (TNF) inhibitor. The percentage of patients with RA plus SCP who achieved American College of Rheumatology (ACR) 20/50/70 scores were all about 10% lower than for patients with RA alone, and about 15% fewer patients achieved remission using a score of less than 2.6 on the DAS28, based on erythrocyte sedimentation rate. There was about a 10% higher withdrawal rate among the RA plus SCP group, compared with those with RA alone, mainly for lack of efficacy, and the RA plus SCP patients had three times the rate of serious infections and twice the rate of nonserious infections of typical RA patients.
Impact on choice of therapy
Clinicians have questioned whether multimorbidities should affect the choice of RA therapy, Dr. Curtis said. One of the most vexing scenarios has been in patients with a history of cancer, he noted. There have been five studies worldwide looking at RA therapy in this population. One from Sweden (Ann Rheum Dis. 2015 Dec;74[12]:2137-43), of 240 breast cancer survivors, found no difference in the occurrence or hazard ratio of recurrent breast cancer between those treated with TNF inhibitors versus those who were not. Another study coauthored by Dr. Curtis found similar results (Arthritis Rheumatol. 2016 Dec;68[10]:2403–11).
According to the ACR’s 2015 treatment guidelines, “If your RA patient has a previously treated, solid organ malignancy, there’s no restrictions on what you and I should use,” he said. “Basically, treat them like they hadn’t had a history of cancer.” The exception is for patients with previously treated nonmelanoma skin cancer or melanoma, in whom conventional synthetic DMARDs are preferred over biologics or tofacitinib (Xeljanz). In addition, patients with previously treated lymphoproliferative disorders should be given rituximab (Rituxan) – or DMARDs, abatacept (Orencia), or tocilizumab (Actemra) – over TNF inhibitors. “This is good news,” Dr. Curtis said. “It really expands the range of options for patients, now supported by data, who have a history of cancer and bad RA.”
Global Academy for Medical Education and this news organization are owned by the same parent company. Dr. Curtis receives research support or serves as a consultant for Amgen, Bristol-Myers Squibb, Corrona, Lilly, Janssen, Myriad, Pfizer, and Sanofi/Regeneron.
While clinicians are accustomed to managing patients with rheumatoid arthritis and comorbidities, RA patients more frequently have “multimorbidities” – the simultaneous presence of two or more chronic conditions.
“For anyone who sees patients, this is the reality of our lives,” said Jeffrey R. Curtis, MD, at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. Some conditions are “bystanders” that don’t impact RA, some are risk factors for RA, and some can be caused by RA treatments, said Dr. Curtis, professor of medicine and William J. Koopman Professor in Rheumatology and Immunology at the University of Alabama at Birmingham. He discussed several comorbid conditions and their interactions with RA.
Obesity’s toll on disease activity
It’s long been recognized that obesity along with RA makes things worse for patients, he said: “If you have a patient who is obese, with a BMI [body mass index] over 30-35, they’re less likely clinically to achieve low disease activity or remission.”
Obesity also affects biomarkers, he said. The multibiomarker disease activity test, marketed as Vectra DA, incorporates several adipokines in its score, but given any level of RA disease, that score is roughly 5 units higher if someone is obese (Sem Arthritis Rheum. 2017 Aug 2. doi: 10.1016/j.semarthrit.2017.07.010). “The company that manufactures the test is working on an adjustment factor to optimize the role of obesity and what those adipokines are doing to better predict x-ray progression to take this influence into account,” he said. “How we measure obesity and how we’re measuring RA are probably very much affected by this issue.”
RA and the somatization comorbidity phenotype
A second common co-occurrence is what Dr. Curtis calls a somatization comorbidity phenotype (SCP), defined as RA with several other ailments such as fibromyalgia, depression, anxiety, sleep apnea, or neuropathy. “The troubling thing about this is I could cure this patient’s RA tomorrow, but they actually wouldn’t feel better in their overall health because of other things dragging down their function,” he said, noting patients are more concerned about their fatigue and pain than their swollen joint count or DAS28 score.
Dr. Curtis and his colleagues completed a recent analysis that’s in press in Arthritis Research & Therapy of about 800 RA patients in the United States starting certolizumab pegol (Cimzia) to look for how well patients with this phenotype responded to a tumor necrosis factor (TNF) inhibitor. The percentage of patients with RA plus SCP who achieved American College of Rheumatology (ACR) 20/50/70 scores were all about 10% lower than for patients with RA alone, and about 15% fewer patients achieved remission using a score of less than 2.6 on the DAS28, based on erythrocyte sedimentation rate. There was about a 10% higher withdrawal rate among the RA plus SCP group, compared with those with RA alone, mainly for lack of efficacy, and the RA plus SCP patients had three times the rate of serious infections and twice the rate of nonserious infections of typical RA patients.
Impact on choice of therapy
Clinicians have questioned whether multimorbidities should affect the choice of RA therapy, Dr. Curtis said. One of the most vexing scenarios has been in patients with a history of cancer, he noted. There have been five studies worldwide looking at RA therapy in this population. One from Sweden (Ann Rheum Dis. 2015 Dec;74[12]:2137-43), of 240 breast cancer survivors, found no difference in the occurrence or hazard ratio of recurrent breast cancer between those treated with TNF inhibitors versus those who were not. Another study coauthored by Dr. Curtis found similar results (Arthritis Rheumatol. 2016 Dec;68[10]:2403–11).
According to the ACR’s 2015 treatment guidelines, “If your RA patient has a previously treated, solid organ malignancy, there’s no restrictions on what you and I should use,” he said. “Basically, treat them like they hadn’t had a history of cancer.” The exception is for patients with previously treated nonmelanoma skin cancer or melanoma, in whom conventional synthetic DMARDs are preferred over biologics or tofacitinib (Xeljanz). In addition, patients with previously treated lymphoproliferative disorders should be given rituximab (Rituxan) – or DMARDs, abatacept (Orencia), or tocilizumab (Actemra) – over TNF inhibitors. “This is good news,” Dr. Curtis said. “It really expands the range of options for patients, now supported by data, who have a history of cancer and bad RA.”
Global Academy for Medical Education and this news organization are owned by the same parent company. Dr. Curtis receives research support or serves as a consultant for Amgen, Bristol-Myers Squibb, Corrona, Lilly, Janssen, Myriad, Pfizer, and Sanofi/Regeneron.
While clinicians are accustomed to managing patients with rheumatoid arthritis and comorbidities, RA patients more frequently have “multimorbidities” – the simultaneous presence of two or more chronic conditions.
“For anyone who sees patients, this is the reality of our lives,” said Jeffrey R. Curtis, MD, at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. Some conditions are “bystanders” that don’t impact RA, some are risk factors for RA, and some can be caused by RA treatments, said Dr. Curtis, professor of medicine and William J. Koopman Professor in Rheumatology and Immunology at the University of Alabama at Birmingham. He discussed several comorbid conditions and their interactions with RA.
Obesity’s toll on disease activity
It’s long been recognized that obesity along with RA makes things worse for patients, he said: “If you have a patient who is obese, with a BMI [body mass index] over 30-35, they’re less likely clinically to achieve low disease activity or remission.”
Obesity also affects biomarkers, he said. The multibiomarker disease activity test, marketed as Vectra DA, incorporates several adipokines in its score, but given any level of RA disease, that score is roughly 5 units higher if someone is obese (Sem Arthritis Rheum. 2017 Aug 2. doi: 10.1016/j.semarthrit.2017.07.010). “The company that manufactures the test is working on an adjustment factor to optimize the role of obesity and what those adipokines are doing to better predict x-ray progression to take this influence into account,” he said. “How we measure obesity and how we’re measuring RA are probably very much affected by this issue.”
RA and the somatization comorbidity phenotype
A second common co-occurrence is what Dr. Curtis calls a somatization comorbidity phenotype (SCP), defined as RA with several other ailments such as fibromyalgia, depression, anxiety, sleep apnea, or neuropathy. “The troubling thing about this is I could cure this patient’s RA tomorrow, but they actually wouldn’t feel better in their overall health because of other things dragging down their function,” he said, noting patients are more concerned about their fatigue and pain than their swollen joint count or DAS28 score.
Dr. Curtis and his colleagues completed a recent analysis that’s in press in Arthritis Research & Therapy of about 800 RA patients in the United States starting certolizumab pegol (Cimzia) to look for how well patients with this phenotype responded to a tumor necrosis factor (TNF) inhibitor. The percentage of patients with RA plus SCP who achieved American College of Rheumatology (ACR) 20/50/70 scores were all about 10% lower than for patients with RA alone, and about 15% fewer patients achieved remission using a score of less than 2.6 on the DAS28, based on erythrocyte sedimentation rate. There was about a 10% higher withdrawal rate among the RA plus SCP group, compared with those with RA alone, mainly for lack of efficacy, and the RA plus SCP patients had three times the rate of serious infections and twice the rate of nonserious infections of typical RA patients.
Impact on choice of therapy
Clinicians have questioned whether multimorbidities should affect the choice of RA therapy, Dr. Curtis said. One of the most vexing scenarios has been in patients with a history of cancer, he noted. There have been five studies worldwide looking at RA therapy in this population. One from Sweden (Ann Rheum Dis. 2015 Dec;74[12]:2137-43), of 240 breast cancer survivors, found no difference in the occurrence or hazard ratio of recurrent breast cancer between those treated with TNF inhibitors versus those who were not. Another study coauthored by Dr. Curtis found similar results (Arthritis Rheumatol. 2016 Dec;68[10]:2403–11).
According to the ACR’s 2015 treatment guidelines, “If your RA patient has a previously treated, solid organ malignancy, there’s no restrictions on what you and I should use,” he said. “Basically, treat them like they hadn’t had a history of cancer.” The exception is for patients with previously treated nonmelanoma skin cancer or melanoma, in whom conventional synthetic DMARDs are preferred over biologics or tofacitinib (Xeljanz). In addition, patients with previously treated lymphoproliferative disorders should be given rituximab (Rituxan) – or DMARDs, abatacept (Orencia), or tocilizumab (Actemra) – over TNF inhibitors. “This is good news,” Dr. Curtis said. “It really expands the range of options for patients, now supported by data, who have a history of cancer and bad RA.”
Global Academy for Medical Education and this news organization are owned by the same parent company. Dr. Curtis receives research support or serves as a consultant for Amgen, Bristol-Myers Squibb, Corrona, Lilly, Janssen, Myriad, Pfizer, and Sanofi/Regeneron.
EXPERT ANALYSIS FROM THE ANNUAL PERSPECTIVES IN RHEUMATIC DISEASES