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Flare of nonradiographic axial SpA occurs often after adalimumab withdrawal for remission
Patients with nonradiographic axial spondyloarthritis (nr-axSpA) who enter remission on adalimumab are likely to relapse if the medication is withdrawn – and many won’t attain remission again, even if the drug is restarted.
However, the findings of the ABILITY-3 trial do offer an intriguing potential, Robert Landewé, MD, PhD, said at the annual meeting of the American College of Rheumatology. About 30% of the study group did maintain remission after adalimumab (Humira) withdrawal, suggesting that at least a portion of these patients can stay in good clinical shape off TNF inhibition.
ABILITY-3 is the successor to ABILITY-1, the 2012 placebo-controlled study that established adalimumab as an effective treatment for nr-axSpA. Adalimumab is approved in the United States for the treatment of ankylosing spondylitis (radiographic axSpA), but not for nr-axSpA.
ABILITY-3 assessed the impact of withdrawing adalimumab from nr-axSpA patients who had attained remission on the medication. It enrolled 673 adults with active disease at baseline and an inadequate response to at least two nonsteroidal anti-inflammatory drugs.
The study commenced with open-label adalimumab at 40 mg every other week for 28 weeks. At that point, the 305 patients who had attained disease remission were randomized to either continued adalimumab at the same dose and schedule or to placebo. Randomized treatment continued for 40 more weeks. Any patient who experienced a flare resumed the drug as rescue therapy. The investigators calculated the number of patients with a disease flare at week 68 as the primary endpoint. The study also examined a number of secondary endpoints, including response measures, time to flare, functional status, quality of life, and remission.
At baseline, patients were a mean of 35 years old, with a mean disease duration of about 7 years. Most (88%) were HLA-B27 positive, and about 60% had elevated C-reactive protein levels.
At 68 weeks, patients who discontinued adalimumab were 77% more likely to have experienced a disease flare than were those who stayed on the drug (83% vs. 57% or 70% vs. 47% with nonresponder imputation; relative risk, 1.77). A time-to-flare analysis found a significant 67% reduction in the risk of flare among those continuing to take adalimumab.
While those who experienced a disease flare were allowed to resume adalimumab, it appeared to be far less effective at that point. After 12 weeks of rescue therapy, only 57% had regained remission, leaving 43% with persistent active disease.
Nearly all of the secondary endpoints were in favor of continuing therapy, Dr. Landewé said, including the Ankylosing Spondyloarthritis Disease Activity Score-inactive disease (ASDAS-ID), ASDAS-major improvement, ASDAS-clinically important improvement; the Assessment in Spondyloarthritis International Society (ASAS) 20% and 40% rates; the ASAS 5/6 and ASAS-partial response rates; the Bath Ankylosing Spondylitis Disease Activity Index 50; and the Bath Ankylosing Spondylitis Functional Index. Only health-related quality of life as measured by the Health Assessment Questionnaire for the Spondyloarthropathies did not significantly improve to a greater extent among those staying on adalimumab.
There were no new or concerning safety signals, Dr. Landewé said. In the placebo-controlled period, there were 10 serious adverse events in the placebo group and 1 – a case of ureterolithiasis – in the adalimumab group. There was one malignancy, which occurred in the placebo group. No patient died during the study.
“These results support the continuation of adalimumab therapy after achieving a sustained remission,” Dr. Landewé said. “But it will be an important research goal to identify predictors for the population in whom treatment may be safely discontinued.”
AbbVie sponsored the study. Dr. Landewé reported relationships with numerous pharmaceutical companies, including AbbVie.
Patients with nonradiographic axial spondyloarthritis (nr-axSpA) who enter remission on adalimumab are likely to relapse if the medication is withdrawn – and many won’t attain remission again, even if the drug is restarted.
However, the findings of the ABILITY-3 trial do offer an intriguing potential, Robert Landewé, MD, PhD, said at the annual meeting of the American College of Rheumatology. About 30% of the study group did maintain remission after adalimumab (Humira) withdrawal, suggesting that at least a portion of these patients can stay in good clinical shape off TNF inhibition.
ABILITY-3 is the successor to ABILITY-1, the 2012 placebo-controlled study that established adalimumab as an effective treatment for nr-axSpA. Adalimumab is approved in the United States for the treatment of ankylosing spondylitis (radiographic axSpA), but not for nr-axSpA.
ABILITY-3 assessed the impact of withdrawing adalimumab from nr-axSpA patients who had attained remission on the medication. It enrolled 673 adults with active disease at baseline and an inadequate response to at least two nonsteroidal anti-inflammatory drugs.
The study commenced with open-label adalimumab at 40 mg every other week for 28 weeks. At that point, the 305 patients who had attained disease remission were randomized to either continued adalimumab at the same dose and schedule or to placebo. Randomized treatment continued for 40 more weeks. Any patient who experienced a flare resumed the drug as rescue therapy. The investigators calculated the number of patients with a disease flare at week 68 as the primary endpoint. The study also examined a number of secondary endpoints, including response measures, time to flare, functional status, quality of life, and remission.
At baseline, patients were a mean of 35 years old, with a mean disease duration of about 7 years. Most (88%) were HLA-B27 positive, and about 60% had elevated C-reactive protein levels.
At 68 weeks, patients who discontinued adalimumab were 77% more likely to have experienced a disease flare than were those who stayed on the drug (83% vs. 57% or 70% vs. 47% with nonresponder imputation; relative risk, 1.77). A time-to-flare analysis found a significant 67% reduction in the risk of flare among those continuing to take adalimumab.
While those who experienced a disease flare were allowed to resume adalimumab, it appeared to be far less effective at that point. After 12 weeks of rescue therapy, only 57% had regained remission, leaving 43% with persistent active disease.
Nearly all of the secondary endpoints were in favor of continuing therapy, Dr. Landewé said, including the Ankylosing Spondyloarthritis Disease Activity Score-inactive disease (ASDAS-ID), ASDAS-major improvement, ASDAS-clinically important improvement; the Assessment in Spondyloarthritis International Society (ASAS) 20% and 40% rates; the ASAS 5/6 and ASAS-partial response rates; the Bath Ankylosing Spondylitis Disease Activity Index 50; and the Bath Ankylosing Spondylitis Functional Index. Only health-related quality of life as measured by the Health Assessment Questionnaire for the Spondyloarthropathies did not significantly improve to a greater extent among those staying on adalimumab.
There were no new or concerning safety signals, Dr. Landewé said. In the placebo-controlled period, there were 10 serious adverse events in the placebo group and 1 – a case of ureterolithiasis – in the adalimumab group. There was one malignancy, which occurred in the placebo group. No patient died during the study.
“These results support the continuation of adalimumab therapy after achieving a sustained remission,” Dr. Landewé said. “But it will be an important research goal to identify predictors for the population in whom treatment may be safely discontinued.”
AbbVie sponsored the study. Dr. Landewé reported relationships with numerous pharmaceutical companies, including AbbVie.
Patients with nonradiographic axial spondyloarthritis (nr-axSpA) who enter remission on adalimumab are likely to relapse if the medication is withdrawn – and many won’t attain remission again, even if the drug is restarted.
However, the findings of the ABILITY-3 trial do offer an intriguing potential, Robert Landewé, MD, PhD, said at the annual meeting of the American College of Rheumatology. About 30% of the study group did maintain remission after adalimumab (Humira) withdrawal, suggesting that at least a portion of these patients can stay in good clinical shape off TNF inhibition.
ABILITY-3 is the successor to ABILITY-1, the 2012 placebo-controlled study that established adalimumab as an effective treatment for nr-axSpA. Adalimumab is approved in the United States for the treatment of ankylosing spondylitis (radiographic axSpA), but not for nr-axSpA.
ABILITY-3 assessed the impact of withdrawing adalimumab from nr-axSpA patients who had attained remission on the medication. It enrolled 673 adults with active disease at baseline and an inadequate response to at least two nonsteroidal anti-inflammatory drugs.
The study commenced with open-label adalimumab at 40 mg every other week for 28 weeks. At that point, the 305 patients who had attained disease remission were randomized to either continued adalimumab at the same dose and schedule or to placebo. Randomized treatment continued for 40 more weeks. Any patient who experienced a flare resumed the drug as rescue therapy. The investigators calculated the number of patients with a disease flare at week 68 as the primary endpoint. The study also examined a number of secondary endpoints, including response measures, time to flare, functional status, quality of life, and remission.
At baseline, patients were a mean of 35 years old, with a mean disease duration of about 7 years. Most (88%) were HLA-B27 positive, and about 60% had elevated C-reactive protein levels.
At 68 weeks, patients who discontinued adalimumab were 77% more likely to have experienced a disease flare than were those who stayed on the drug (83% vs. 57% or 70% vs. 47% with nonresponder imputation; relative risk, 1.77). A time-to-flare analysis found a significant 67% reduction in the risk of flare among those continuing to take adalimumab.
While those who experienced a disease flare were allowed to resume adalimumab, it appeared to be far less effective at that point. After 12 weeks of rescue therapy, only 57% had regained remission, leaving 43% with persistent active disease.
Nearly all of the secondary endpoints were in favor of continuing therapy, Dr. Landewé said, including the Ankylosing Spondyloarthritis Disease Activity Score-inactive disease (ASDAS-ID), ASDAS-major improvement, ASDAS-clinically important improvement; the Assessment in Spondyloarthritis International Society (ASAS) 20% and 40% rates; the ASAS 5/6 and ASAS-partial response rates; the Bath Ankylosing Spondylitis Disease Activity Index 50; and the Bath Ankylosing Spondylitis Functional Index. Only health-related quality of life as measured by the Health Assessment Questionnaire for the Spondyloarthropathies did not significantly improve to a greater extent among those staying on adalimumab.
There were no new or concerning safety signals, Dr. Landewé said. In the placebo-controlled period, there were 10 serious adverse events in the placebo group and 1 – a case of ureterolithiasis – in the adalimumab group. There was one malignancy, which occurred in the placebo group. No patient died during the study.
“These results support the continuation of adalimumab therapy after achieving a sustained remission,” Dr. Landewé said. “But it will be an important research goal to identify predictors for the population in whom treatment may be safely discontinued.”
AbbVie sponsored the study. Dr. Landewé reported relationships with numerous pharmaceutical companies, including AbbVie.
REPORTING FROM ACR 2017
Key clinical point:
Major finding: Withdrawing adalimumab increased the risk of flare by 77%.
Study details: The study randomized 305 patients in remission to placebo or 40 mg adalimumab every other week.
Disclosures: AbbVie sponsored the study. The presenter reported relationships with numerous pharmaceutical companies, including AbbVie.
Source: Landewé R et al. ACR 2017 Abstract 1787
Expert discusses risks of biosimilars in rheumatology
SAN DIEGO – If you perceive that the use of biosimilars for rheumatic diseases hasn’t gained the traction one would expect, you’re not alone. In the opinion of J. Eugene Huffstutter, MD, the expected risks of biosimilar products have clinicians concerned, especially when it comes to immunologic characteristics.
“We’ve all had patients on biologics for years: Everything’s fine, but then the patient has an infusion reaction,” Dr. Huffstutter said at the annual meeting of the American College of Rheumatology. “I’ve had it happen with the first infusion of a biologic and I’ve had it with the 20th infusion of that same biologic product. It’s impossible to predict.”
Other unforeseen risks of biosimilars include the impact on pharmacovigilance, manufacturing, and politics. “What if our government says we want to use this agent or that agent? Or, what if it advises everyone to use the bio-originator? Then there are coverage challenges,” he said. “How are the insurance companies going to look at this? Then there are corporate impacts. The companies that make biosimilars have invested a tremendous amount of resources to bring these to market. We have a huge market in the U.S., but the uptake has been very slow. So are they going to say, ‘We’re going to take our resources and do something else?’ ”
Practice protocols for using biosimilars vary depending on your practice environment. For example, if biosimilars are administered by a freestanding practice, “you have to depend a lot on your state laws in terms of what the pharmacist is able to do,” said Dr. Huffstutter, who is also the past president of the Tennessee Rheumatology Society. “What are the patient support programs available for that biosimilar compared with bio-originator? What do the insurance contracts say in terms of can you get this filled or not? What’s the formulary status? How well do physicians in your community accept biosimilars? More importantly, how do your patients feel about biosimilars? I think they’ve been left out of this whole discussion.”
Dr. Huffstutter disclosed that he has received research support from GlaxoSmithKline, Pfizer, and UCB. He is also a member of the speakers bureau and/or is an adviser to Janssen, Lilly, Pfizer, Genentech, Novartis, Regeneron, and UCB.
SAN DIEGO – If you perceive that the use of biosimilars for rheumatic diseases hasn’t gained the traction one would expect, you’re not alone. In the opinion of J. Eugene Huffstutter, MD, the expected risks of biosimilar products have clinicians concerned, especially when it comes to immunologic characteristics.
“We’ve all had patients on biologics for years: Everything’s fine, but then the patient has an infusion reaction,” Dr. Huffstutter said at the annual meeting of the American College of Rheumatology. “I’ve had it happen with the first infusion of a biologic and I’ve had it with the 20th infusion of that same biologic product. It’s impossible to predict.”
Other unforeseen risks of biosimilars include the impact on pharmacovigilance, manufacturing, and politics. “What if our government says we want to use this agent or that agent? Or, what if it advises everyone to use the bio-originator? Then there are coverage challenges,” he said. “How are the insurance companies going to look at this? Then there are corporate impacts. The companies that make biosimilars have invested a tremendous amount of resources to bring these to market. We have a huge market in the U.S., but the uptake has been very slow. So are they going to say, ‘We’re going to take our resources and do something else?’ ”
Practice protocols for using biosimilars vary depending on your practice environment. For example, if biosimilars are administered by a freestanding practice, “you have to depend a lot on your state laws in terms of what the pharmacist is able to do,” said Dr. Huffstutter, who is also the past president of the Tennessee Rheumatology Society. “What are the patient support programs available for that biosimilar compared with bio-originator? What do the insurance contracts say in terms of can you get this filled or not? What’s the formulary status? How well do physicians in your community accept biosimilars? More importantly, how do your patients feel about biosimilars? I think they’ve been left out of this whole discussion.”
Dr. Huffstutter disclosed that he has received research support from GlaxoSmithKline, Pfizer, and UCB. He is also a member of the speakers bureau and/or is an adviser to Janssen, Lilly, Pfizer, Genentech, Novartis, Regeneron, and UCB.
SAN DIEGO – If you perceive that the use of biosimilars for rheumatic diseases hasn’t gained the traction one would expect, you’re not alone. In the opinion of J. Eugene Huffstutter, MD, the expected risks of biosimilar products have clinicians concerned, especially when it comes to immunologic characteristics.
“We’ve all had patients on biologics for years: Everything’s fine, but then the patient has an infusion reaction,” Dr. Huffstutter said at the annual meeting of the American College of Rheumatology. “I’ve had it happen with the first infusion of a biologic and I’ve had it with the 20th infusion of that same biologic product. It’s impossible to predict.”
Other unforeseen risks of biosimilars include the impact on pharmacovigilance, manufacturing, and politics. “What if our government says we want to use this agent or that agent? Or, what if it advises everyone to use the bio-originator? Then there are coverage challenges,” he said. “How are the insurance companies going to look at this? Then there are corporate impacts. The companies that make biosimilars have invested a tremendous amount of resources to bring these to market. We have a huge market in the U.S., but the uptake has been very slow. So are they going to say, ‘We’re going to take our resources and do something else?’ ”
Practice protocols for using biosimilars vary depending on your practice environment. For example, if biosimilars are administered by a freestanding practice, “you have to depend a lot on your state laws in terms of what the pharmacist is able to do,” said Dr. Huffstutter, who is also the past president of the Tennessee Rheumatology Society. “What are the patient support programs available for that biosimilar compared with bio-originator? What do the insurance contracts say in terms of can you get this filled or not? What’s the formulary status? How well do physicians in your community accept biosimilars? More importantly, how do your patients feel about biosimilars? I think they’ve been left out of this whole discussion.”
Dr. Huffstutter disclosed that he has received research support from GlaxoSmithKline, Pfizer, and UCB. He is also a member of the speakers bureau and/or is an adviser to Janssen, Lilly, Pfizer, Genentech, Novartis, Regeneron, and UCB.
EXPERT ANALYSIS FROM ACR 2017
VIDEO: Beware of over-relying on MRI findings in axSpA
SAN DIEGO – Healthy individuals can show signs of spinal and pelvic inflammation on MRI, but these scans can be misleading if relied on to make a diagnosis of axial spondyloarthritis, according to findings from three separate studies at the annual meeting of the American College of Rheumatology.
“Don’t rely on MRI alone is our message,” said Robert Landewé, MD, PhD, of the University of Amsterdam, who was a coauthor of one of the three studies. “A positive MRI may occur in individuals that are completely healthy. We need to make sure that not too many patients with chronic lower back pain are diagnosed with a disease they don’t have.”
The axial form of spondyloarthritis (axSpA) affects the spinal and pelvic joints of an estimated 1.4% of the U.S. population, and the term encompasses the diagnosis of ankylosing spondylitis (0.5% of U.S. population) in which advanced sacroiliitis is seen on conventional radiography, according to the ACR. Axial SpA is particularly common in young people, especially males, in their teens and 20s.
Researchers believe that MRI scans can misleadingly suggest that patients have the condition. “We know that MRI is a sensitive method, but there’s a lack of data regarding its specificity,” Thomas Renson, MD, of Ghent (Belgium) University, said at a press conference during the meeting.
Dr. Landewé led a study that compared MRIs of sacroiliac joints in 47 healthy people, 47 axSpA patients matched for gender and age, 47 chronic back pain patients, 7 women with postpartum back pain, and 24 frequent runners. Positive MRIs were common in the axSpA patients (43 of 47), but they were also found in healthy people (11 of 47), chronic back pain patients (3 of 47), frequent runners (3 of 24), and women with postpartum back pain (4 of 7).
In another study, Dr. Renson and his colleagues sought to understand whether a sustained period of intense physical activity affected spinal findings in 22 healthy military recruits who did not have SpA.
However, there was a statistically significant increase of combined structural and inflammatory lesions (P = .038) from baseline to post training.
The findings underscore “the importance of interpretation of imaging in the right clinical context,” Dr. Renson said, since they point to the possibility of an incorrect diagnosis “even in a young, active population.”
Another study, led by Ulrich Weber, MD, of King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark, sought to understand levels of normal low-grade BME in 20 amateur runners (8 men) and 22 professional Danish hockey players (all men). On average, the researchers found signs of BME in 3.1 sacroiliac joint quadrants in the runners before and after they ran a race. Hockey players were scanned at the end of the competitive season and showed signs of BME in an average of 3.6 sacroiliac joint quadrants.
In an interview, Dr. Landewé said the studies point to how common positive MRIs are in healthy people. “It was far higher than we would have thought 10 years ago,” he said.
Are MRIs still useful then? Dr. Weber said MRI scans are still helpful in axSpA diagnoses even though they have major limitations. “The imaging method is the only one that’s halfway reliable,” he said. “These joints are deep in the body, so we have virtually no clinical ways to diagnose this.”
However, Dr. Landewé said, “you should do it only when you have sufficient suspicion of spondyloarthritis” – due to accompanying conditions such as positive family history, acute anterior uveitis, psoriasis, or peripheral arthritis – and not just when a patient has chronic back pain.
Dr. Renson reported having no relevant disclosures; two of his coauthors reported extensive disclosures. Dr. Weber and his coauthors reported having no relevant disclosures. Dr. Landewé reported having no relevant disclosures; several of his coauthors reported various disclosures. Funding for the studies was not reported.
SAN DIEGO – Healthy individuals can show signs of spinal and pelvic inflammation on MRI, but these scans can be misleading if relied on to make a diagnosis of axial spondyloarthritis, according to findings from three separate studies at the annual meeting of the American College of Rheumatology.
“Don’t rely on MRI alone is our message,” said Robert Landewé, MD, PhD, of the University of Amsterdam, who was a coauthor of one of the three studies. “A positive MRI may occur in individuals that are completely healthy. We need to make sure that not too many patients with chronic lower back pain are diagnosed with a disease they don’t have.”
The axial form of spondyloarthritis (axSpA) affects the spinal and pelvic joints of an estimated 1.4% of the U.S. population, and the term encompasses the diagnosis of ankylosing spondylitis (0.5% of U.S. population) in which advanced sacroiliitis is seen on conventional radiography, according to the ACR. Axial SpA is particularly common in young people, especially males, in their teens and 20s.
Researchers believe that MRI scans can misleadingly suggest that patients have the condition. “We know that MRI is a sensitive method, but there’s a lack of data regarding its specificity,” Thomas Renson, MD, of Ghent (Belgium) University, said at a press conference during the meeting.
Dr. Landewé led a study that compared MRIs of sacroiliac joints in 47 healthy people, 47 axSpA patients matched for gender and age, 47 chronic back pain patients, 7 women with postpartum back pain, and 24 frequent runners. Positive MRIs were common in the axSpA patients (43 of 47), but they were also found in healthy people (11 of 47), chronic back pain patients (3 of 47), frequent runners (3 of 24), and women with postpartum back pain (4 of 7).
In another study, Dr. Renson and his colleagues sought to understand whether a sustained period of intense physical activity affected spinal findings in 22 healthy military recruits who did not have SpA.
However, there was a statistically significant increase of combined structural and inflammatory lesions (P = .038) from baseline to post training.
The findings underscore “the importance of interpretation of imaging in the right clinical context,” Dr. Renson said, since they point to the possibility of an incorrect diagnosis “even in a young, active population.”
Another study, led by Ulrich Weber, MD, of King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark, sought to understand levels of normal low-grade BME in 20 amateur runners (8 men) and 22 professional Danish hockey players (all men). On average, the researchers found signs of BME in 3.1 sacroiliac joint quadrants in the runners before and after they ran a race. Hockey players were scanned at the end of the competitive season and showed signs of BME in an average of 3.6 sacroiliac joint quadrants.
In an interview, Dr. Landewé said the studies point to how common positive MRIs are in healthy people. “It was far higher than we would have thought 10 years ago,” he said.
Are MRIs still useful then? Dr. Weber said MRI scans are still helpful in axSpA diagnoses even though they have major limitations. “The imaging method is the only one that’s halfway reliable,” he said. “These joints are deep in the body, so we have virtually no clinical ways to diagnose this.”
However, Dr. Landewé said, “you should do it only when you have sufficient suspicion of spondyloarthritis” – due to accompanying conditions such as positive family history, acute anterior uveitis, psoriasis, or peripheral arthritis – and not just when a patient has chronic back pain.
Dr. Renson reported having no relevant disclosures; two of his coauthors reported extensive disclosures. Dr. Weber and his coauthors reported having no relevant disclosures. Dr. Landewé reported having no relevant disclosures; several of his coauthors reported various disclosures. Funding for the studies was not reported.
SAN DIEGO – Healthy individuals can show signs of spinal and pelvic inflammation on MRI, but these scans can be misleading if relied on to make a diagnosis of axial spondyloarthritis, according to findings from three separate studies at the annual meeting of the American College of Rheumatology.
“Don’t rely on MRI alone is our message,” said Robert Landewé, MD, PhD, of the University of Amsterdam, who was a coauthor of one of the three studies. “A positive MRI may occur in individuals that are completely healthy. We need to make sure that not too many patients with chronic lower back pain are diagnosed with a disease they don’t have.”
The axial form of spondyloarthritis (axSpA) affects the spinal and pelvic joints of an estimated 1.4% of the U.S. population, and the term encompasses the diagnosis of ankylosing spondylitis (0.5% of U.S. population) in which advanced sacroiliitis is seen on conventional radiography, according to the ACR. Axial SpA is particularly common in young people, especially males, in their teens and 20s.
Researchers believe that MRI scans can misleadingly suggest that patients have the condition. “We know that MRI is a sensitive method, but there’s a lack of data regarding its specificity,” Thomas Renson, MD, of Ghent (Belgium) University, said at a press conference during the meeting.
Dr. Landewé led a study that compared MRIs of sacroiliac joints in 47 healthy people, 47 axSpA patients matched for gender and age, 47 chronic back pain patients, 7 women with postpartum back pain, and 24 frequent runners. Positive MRIs were common in the axSpA patients (43 of 47), but they were also found in healthy people (11 of 47), chronic back pain patients (3 of 47), frequent runners (3 of 24), and women with postpartum back pain (4 of 7).
In another study, Dr. Renson and his colleagues sought to understand whether a sustained period of intense physical activity affected spinal findings in 22 healthy military recruits who did not have SpA.
However, there was a statistically significant increase of combined structural and inflammatory lesions (P = .038) from baseline to post training.
The findings underscore “the importance of interpretation of imaging in the right clinical context,” Dr. Renson said, since they point to the possibility of an incorrect diagnosis “even in a young, active population.”
Another study, led by Ulrich Weber, MD, of King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark, sought to understand levels of normal low-grade BME in 20 amateur runners (8 men) and 22 professional Danish hockey players (all men). On average, the researchers found signs of BME in 3.1 sacroiliac joint quadrants in the runners before and after they ran a race. Hockey players were scanned at the end of the competitive season and showed signs of BME in an average of 3.6 sacroiliac joint quadrants.
In an interview, Dr. Landewé said the studies point to how common positive MRIs are in healthy people. “It was far higher than we would have thought 10 years ago,” he said.
Are MRIs still useful then? Dr. Weber said MRI scans are still helpful in axSpA diagnoses even though they have major limitations. “The imaging method is the only one that’s halfway reliable,” he said. “These joints are deep in the body, so we have virtually no clinical ways to diagnose this.”
However, Dr. Landewé said, “you should do it only when you have sufficient suspicion of spondyloarthritis” – due to accompanying conditions such as positive family history, acute anterior uveitis, psoriasis, or peripheral arthritis – and not just when a patient has chronic back pain.
Dr. Renson reported having no relevant disclosures; two of his coauthors reported extensive disclosures. Dr. Weber and his coauthors reported having no relevant disclosures. Dr. Landewé reported having no relevant disclosures; several of his coauthors reported various disclosures. Funding for the studies was not reported.
AT ACR 2017
VIDEO: Obesity linked to worse outcomes in axial spondyloarthropathy
SAN DIEGO – Among patients with axial spondyloarthropathy, higher BMI and obesity independently predicts worse disease outcomes, according to results from a registry study.
“Obesity is one of the biggest public health challenges facing us in the 21st century,” lead study author Gillian Fitzgerald, MD, said in an interview in advance of the annual meeting of the American College of Rheumatology.
“Traditionally, we have a perception of patients with axial SpA being of normal or even thin body habitus. However, recent studies have indicated that this is not the case and that obesity is prevalent in axial SpA patients. The negative consequences of obesity in the general population are well documented, with affected patients suffering greater morbidity and mortality.”
Dr. Fitzgerald, of St. James’s Hospital, Dublin, Ireland, noted that research to date in axial SpA indicates that disease outcomes may be worse in obese patients. However, existing literature looking at obesity in axial SpA is relatively sparse. In an effort to clarify this issue, she and her associates evaluated 683 patients from the Ankylosing Spondylitis Registry of Ireland (ASRI), which is designed to provide descriptive epidemiological data on the Irish axSpA population via standardized clinical assessments and structured interviews. The mean age of the 683 patients enrolled as of June 2017 was 46, the majority (77%) were men, their mean disease duration was 19 years, and their mean delay to diagnosis was nine years. Most (79%) fulfilled Modified New York modified criteria, their mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 3.9, their mean Bath Ankylosing Spondylitis Metrology Index (BASMI) was 3.6, their mean Bath Ankylosing Spondylitis Functional Index (BASFI) was 3.6 and their mean Health Assessment Questionnaire (HAQ) was 0.52.
Based on WHO criteria, the cohort’s mean BMI was 27.8 kg/m2. Of these, 38.9% were overweight and 28.4% were obese. “Indeed, only 32% of the cohort have a healthy BMI,” Dr. Fitzgerald commented. “When we looked at the relationship between BMI and disease outcomes, we found that obese patients had more severe disease than their normal weight and overweight counterparts, with higher measures of disease activity, quality of life, disability and function, as well as worse spinal mobility.”
The researchers also observed that the prevalence of smoking was lower in obese patients, compared with normal weight patients (18% vs. 38, respectively). In univariable linear regression, BMI and obesity were associated with higher BASDAI, BASMI, BASFI and HAQ scores. In multivariable regression analysis, only obesity remained an independent predictor of higher disease activity and worse function (P less than .01).
“As clinicians, we are always looking for ways to reduce the burden of disease that patients carry and to improve outcomes,” Dr. Fitzgerald said. “In this study, we demonstrated that over two-thirds of our axial SpA patients are either overweight or obese, and that these patients have more severe disease. Further research is needed to clarify this relationship between obesity and disease severity; in particular, the effect of losing weight on disease outcomes needs to be clarified. However, when devising treatment plans for axial SpA patients, this study provides rheumatologists with a strong rationale to include strategies to actively control weight.”
She acknowledged that the study’s cross-sectional design is a limitation. “This means cause and effect can’t be determined exclusively from this study; therefore, prospective studies are required to further clarify this relationship that we have noted between obesity and disease outcomes.”
ASRI is funded by an unrestricted grant from AbbVie and Pfizer. Dr. Fitzgerald disclosed having received research support from AbbVie.
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SAN DIEGO – Among patients with axial spondyloarthropathy, higher BMI and obesity independently predicts worse disease outcomes, according to results from a registry study.
“Obesity is one of the biggest public health challenges facing us in the 21st century,” lead study author Gillian Fitzgerald, MD, said in an interview in advance of the annual meeting of the American College of Rheumatology.
“Traditionally, we have a perception of patients with axial SpA being of normal or even thin body habitus. However, recent studies have indicated that this is not the case and that obesity is prevalent in axial SpA patients. The negative consequences of obesity in the general population are well documented, with affected patients suffering greater morbidity and mortality.”
Dr. Fitzgerald, of St. James’s Hospital, Dublin, Ireland, noted that research to date in axial SpA indicates that disease outcomes may be worse in obese patients. However, existing literature looking at obesity in axial SpA is relatively sparse. In an effort to clarify this issue, she and her associates evaluated 683 patients from the Ankylosing Spondylitis Registry of Ireland (ASRI), which is designed to provide descriptive epidemiological data on the Irish axSpA population via standardized clinical assessments and structured interviews. The mean age of the 683 patients enrolled as of June 2017 was 46, the majority (77%) were men, their mean disease duration was 19 years, and their mean delay to diagnosis was nine years. Most (79%) fulfilled Modified New York modified criteria, their mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 3.9, their mean Bath Ankylosing Spondylitis Metrology Index (BASMI) was 3.6, their mean Bath Ankylosing Spondylitis Functional Index (BASFI) was 3.6 and their mean Health Assessment Questionnaire (HAQ) was 0.52.
Based on WHO criteria, the cohort’s mean BMI was 27.8 kg/m2. Of these, 38.9% were overweight and 28.4% were obese. “Indeed, only 32% of the cohort have a healthy BMI,” Dr. Fitzgerald commented. “When we looked at the relationship between BMI and disease outcomes, we found that obese patients had more severe disease than their normal weight and overweight counterparts, with higher measures of disease activity, quality of life, disability and function, as well as worse spinal mobility.”
The researchers also observed that the prevalence of smoking was lower in obese patients, compared with normal weight patients (18% vs. 38, respectively). In univariable linear regression, BMI and obesity were associated with higher BASDAI, BASMI, BASFI and HAQ scores. In multivariable regression analysis, only obesity remained an independent predictor of higher disease activity and worse function (P less than .01).
“As clinicians, we are always looking for ways to reduce the burden of disease that patients carry and to improve outcomes,” Dr. Fitzgerald said. “In this study, we demonstrated that over two-thirds of our axial SpA patients are either overweight or obese, and that these patients have more severe disease. Further research is needed to clarify this relationship between obesity and disease severity; in particular, the effect of losing weight on disease outcomes needs to be clarified. However, when devising treatment plans for axial SpA patients, this study provides rheumatologists with a strong rationale to include strategies to actively control weight.”
She acknowledged that the study’s cross-sectional design is a limitation. “This means cause and effect can’t be determined exclusively from this study; therefore, prospective studies are required to further clarify this relationship that we have noted between obesity and disease outcomes.”
ASRI is funded by an unrestricted grant from AbbVie and Pfizer. Dr. Fitzgerald disclosed having received research support from AbbVie.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN DIEGO – Among patients with axial spondyloarthropathy, higher BMI and obesity independently predicts worse disease outcomes, according to results from a registry study.
“Obesity is one of the biggest public health challenges facing us in the 21st century,” lead study author Gillian Fitzgerald, MD, said in an interview in advance of the annual meeting of the American College of Rheumatology.
“Traditionally, we have a perception of patients with axial SpA being of normal or even thin body habitus. However, recent studies have indicated that this is not the case and that obesity is prevalent in axial SpA patients. The negative consequences of obesity in the general population are well documented, with affected patients suffering greater morbidity and mortality.”
Dr. Fitzgerald, of St. James’s Hospital, Dublin, Ireland, noted that research to date in axial SpA indicates that disease outcomes may be worse in obese patients. However, existing literature looking at obesity in axial SpA is relatively sparse. In an effort to clarify this issue, she and her associates evaluated 683 patients from the Ankylosing Spondylitis Registry of Ireland (ASRI), which is designed to provide descriptive epidemiological data on the Irish axSpA population via standardized clinical assessments and structured interviews. The mean age of the 683 patients enrolled as of June 2017 was 46, the majority (77%) were men, their mean disease duration was 19 years, and their mean delay to diagnosis was nine years. Most (79%) fulfilled Modified New York modified criteria, their mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 3.9, their mean Bath Ankylosing Spondylitis Metrology Index (BASMI) was 3.6, their mean Bath Ankylosing Spondylitis Functional Index (BASFI) was 3.6 and their mean Health Assessment Questionnaire (HAQ) was 0.52.
Based on WHO criteria, the cohort’s mean BMI was 27.8 kg/m2. Of these, 38.9% were overweight and 28.4% were obese. “Indeed, only 32% of the cohort have a healthy BMI,” Dr. Fitzgerald commented. “When we looked at the relationship between BMI and disease outcomes, we found that obese patients had more severe disease than their normal weight and overweight counterparts, with higher measures of disease activity, quality of life, disability and function, as well as worse spinal mobility.”
The researchers also observed that the prevalence of smoking was lower in obese patients, compared with normal weight patients (18% vs. 38, respectively). In univariable linear regression, BMI and obesity were associated with higher BASDAI, BASMI, BASFI and HAQ scores. In multivariable regression analysis, only obesity remained an independent predictor of higher disease activity and worse function (P less than .01).
“As clinicians, we are always looking for ways to reduce the burden of disease that patients carry and to improve outcomes,” Dr. Fitzgerald said. “In this study, we demonstrated that over two-thirds of our axial SpA patients are either overweight or obese, and that these patients have more severe disease. Further research is needed to clarify this relationship between obesity and disease severity; in particular, the effect of losing weight on disease outcomes needs to be clarified. However, when devising treatment plans for axial SpA patients, this study provides rheumatologists with a strong rationale to include strategies to actively control weight.”
She acknowledged that the study’s cross-sectional design is a limitation. “This means cause and effect can’t be determined exclusively from this study; therefore, prospective studies are required to further clarify this relationship that we have noted between obesity and disease outcomes.”
ASRI is funded by an unrestricted grant from AbbVie and Pfizer. Dr. Fitzgerald disclosed having received research support from AbbVie.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ACR 2017
Key clinical point: Obese patients with axial spondyloarthropathy have worse disease outcomes.
Major finding: In multivariable regression analysis, only obesity remained an independent predictor of higher disease activity and worse function (P less than .01).
Study details: A cross-sectional study of 683 patients with axial spondyloarthropathy.
Disclosures: ASRI is funded by an unrestricted grant from AbbVie and Pfizer. Dr. Fitzgerald disclosed having received research support from AbbVie Hopkins.
Biosimilars poised to save $54 billion over the next decade
Biosimilars could reduce overall spending on biologic products by $54 billion from 2017 to 2026, according to new research from the Rand Corp.
Given the level of uncertainty surrounding the biosimilars market, however, the range of savings could be as low at $24 billion or as high as $150 billion.
“Because of limited U.S. experience with biosimilars, the key assumptions on market share and biosimilar prices are ‘best guesses’ based on anecdotes or professional opinion,” Andrew Mulcahy, PhD, a health policy researcher at Rand, and his colleagues, wrote in a perspective report.
“Whether actual cost savings end up above or below our baseline estimate hinges in large part on whether manufacturers continue to have a business case to invest in developing and marketing biosimilars,” the authors noted, citing a number of areas, including intellectual property litigation, payment, price competition, nonprice competition from reference biologic manufacturers, naming convention, and interchangeability.
Getting over these hurdles could require legislative or regulatory solutions.
“The pervasive uncertainty in the U.S. biosimilar market – including questions as to whether the market will be sustainable and lead to cost savings, as intended – presents two choices for policymakers,” Dr. Mulcahy and his colleagues wrote. “One strategy is to let the market continue to develop under current policies,” with stability coming from experience.
The alternative could be policy levers to “help steer the U.S. biosimilar market more quickly to a sustainable, competitive state,” they continued. “For example, regulators at the FDA could experiment with new approaches to provide stronger, earlier signals through guidance documents or other mechanisms on expectations surrounding interchangeability and other topics.”
The FDA appears to be moving on the latter. In an Oct. 23 blog post, FDA Commissioner Scott Gottlieb, MD, and Leah Christl, PhD, associate director for therapeutic biologics in the office of new drugs at the FDA’s Center for Drug Evaluation and Research, outlined a number of recent tools to help biosimilar adoption. The resources provide basics such as the basic definition associated with biosimilars (i.e., what is a biosimilar and a reference product, and what it means to be interchangeable), the standards of approval that biosimilars must go through, and easily accessible information on what the FDA is using to review biosimilarity.
“Next, FDA plans to embark on additional research with health care professionals to learn more about the types of information prescribers need to properly communicate with their patients about biosimilars,” Commissioner Gottlieb and Dr. Christl wrote. “An increase in market competition, offered by a growing complement of biosimilars, may lead to meaningfully reduced costs for both patients and our health care system.”
The Centers for Medicare & Medicaid Services also plays a role in developing policy to spur biosimilar adoption, Dr. Mulcahy and his colleagues wrote. They note work being done by the Medicare Payment Advisory Commission on recommendations that could address payment for physician-administered biosimilars under Part B, as well as incentives in the Part D prescription drug program to steer patients and providers toward lower cost biosimilars when appropriate. CMS changed current payment policy for biosimilars for 2018, which may have an effect.
“Beyond FDA regulation, payment, and coverage, both government and industry could play a role in educating patients and providers about the potential cost savings from biosimilars, much like both groups have done for generic drugs,” they stated. “While our study does not address whether policy action is needed now, it is likely that the answer will become clearer over the next 1 to 3 years as the market continues to develop.”
Biosimilars could reduce overall spending on biologic products by $54 billion from 2017 to 2026, according to new research from the Rand Corp.
Given the level of uncertainty surrounding the biosimilars market, however, the range of savings could be as low at $24 billion or as high as $150 billion.
“Because of limited U.S. experience with biosimilars, the key assumptions on market share and biosimilar prices are ‘best guesses’ based on anecdotes or professional opinion,” Andrew Mulcahy, PhD, a health policy researcher at Rand, and his colleagues, wrote in a perspective report.
“Whether actual cost savings end up above or below our baseline estimate hinges in large part on whether manufacturers continue to have a business case to invest in developing and marketing biosimilars,” the authors noted, citing a number of areas, including intellectual property litigation, payment, price competition, nonprice competition from reference biologic manufacturers, naming convention, and interchangeability.
Getting over these hurdles could require legislative or regulatory solutions.
“The pervasive uncertainty in the U.S. biosimilar market – including questions as to whether the market will be sustainable and lead to cost savings, as intended – presents two choices for policymakers,” Dr. Mulcahy and his colleagues wrote. “One strategy is to let the market continue to develop under current policies,” with stability coming from experience.
The alternative could be policy levers to “help steer the U.S. biosimilar market more quickly to a sustainable, competitive state,” they continued. “For example, regulators at the FDA could experiment with new approaches to provide stronger, earlier signals through guidance documents or other mechanisms on expectations surrounding interchangeability and other topics.”
The FDA appears to be moving on the latter. In an Oct. 23 blog post, FDA Commissioner Scott Gottlieb, MD, and Leah Christl, PhD, associate director for therapeutic biologics in the office of new drugs at the FDA’s Center for Drug Evaluation and Research, outlined a number of recent tools to help biosimilar adoption. The resources provide basics such as the basic definition associated with biosimilars (i.e., what is a biosimilar and a reference product, and what it means to be interchangeable), the standards of approval that biosimilars must go through, and easily accessible information on what the FDA is using to review biosimilarity.
“Next, FDA plans to embark on additional research with health care professionals to learn more about the types of information prescribers need to properly communicate with their patients about biosimilars,” Commissioner Gottlieb and Dr. Christl wrote. “An increase in market competition, offered by a growing complement of biosimilars, may lead to meaningfully reduced costs for both patients and our health care system.”
The Centers for Medicare & Medicaid Services also plays a role in developing policy to spur biosimilar adoption, Dr. Mulcahy and his colleagues wrote. They note work being done by the Medicare Payment Advisory Commission on recommendations that could address payment for physician-administered biosimilars under Part B, as well as incentives in the Part D prescription drug program to steer patients and providers toward lower cost biosimilars when appropriate. CMS changed current payment policy for biosimilars for 2018, which may have an effect.
“Beyond FDA regulation, payment, and coverage, both government and industry could play a role in educating patients and providers about the potential cost savings from biosimilars, much like both groups have done for generic drugs,” they stated. “While our study does not address whether policy action is needed now, it is likely that the answer will become clearer over the next 1 to 3 years as the market continues to develop.”
Biosimilars could reduce overall spending on biologic products by $54 billion from 2017 to 2026, according to new research from the Rand Corp.
Given the level of uncertainty surrounding the biosimilars market, however, the range of savings could be as low at $24 billion or as high as $150 billion.
“Because of limited U.S. experience with biosimilars, the key assumptions on market share and biosimilar prices are ‘best guesses’ based on anecdotes or professional opinion,” Andrew Mulcahy, PhD, a health policy researcher at Rand, and his colleagues, wrote in a perspective report.
“Whether actual cost savings end up above or below our baseline estimate hinges in large part on whether manufacturers continue to have a business case to invest in developing and marketing biosimilars,” the authors noted, citing a number of areas, including intellectual property litigation, payment, price competition, nonprice competition from reference biologic manufacturers, naming convention, and interchangeability.
Getting over these hurdles could require legislative or regulatory solutions.
“The pervasive uncertainty in the U.S. biosimilar market – including questions as to whether the market will be sustainable and lead to cost savings, as intended – presents two choices for policymakers,” Dr. Mulcahy and his colleagues wrote. “One strategy is to let the market continue to develop under current policies,” with stability coming from experience.
The alternative could be policy levers to “help steer the U.S. biosimilar market more quickly to a sustainable, competitive state,” they continued. “For example, regulators at the FDA could experiment with new approaches to provide stronger, earlier signals through guidance documents or other mechanisms on expectations surrounding interchangeability and other topics.”
The FDA appears to be moving on the latter. In an Oct. 23 blog post, FDA Commissioner Scott Gottlieb, MD, and Leah Christl, PhD, associate director for therapeutic biologics in the office of new drugs at the FDA’s Center for Drug Evaluation and Research, outlined a number of recent tools to help biosimilar adoption. The resources provide basics such as the basic definition associated with biosimilars (i.e., what is a biosimilar and a reference product, and what it means to be interchangeable), the standards of approval that biosimilars must go through, and easily accessible information on what the FDA is using to review biosimilarity.
“Next, FDA plans to embark on additional research with health care professionals to learn more about the types of information prescribers need to properly communicate with their patients about biosimilars,” Commissioner Gottlieb and Dr. Christl wrote. “An increase in market competition, offered by a growing complement of biosimilars, may lead to meaningfully reduced costs for both patients and our health care system.”
The Centers for Medicare & Medicaid Services also plays a role in developing policy to spur biosimilar adoption, Dr. Mulcahy and his colleagues wrote. They note work being done by the Medicare Payment Advisory Commission on recommendations that could address payment for physician-administered biosimilars under Part B, as well as incentives in the Part D prescription drug program to steer patients and providers toward lower cost biosimilars when appropriate. CMS changed current payment policy for biosimilars for 2018, which may have an effect.
“Beyond FDA regulation, payment, and coverage, both government and industry could play a role in educating patients and providers about the potential cost savings from biosimilars, much like both groups have done for generic drugs,” they stated. “While our study does not address whether policy action is needed now, it is likely that the answer will become clearer over the next 1 to 3 years as the market continues to develop.”
Golimumab earns new FDA approvals
The U.S. Food and Drug Administration has approved golimumab (Simponi Aria) for use in adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS).
Simponi Aria is an intravenous formulation of golimumab that is already approved for moderate to severe rheumatoid arthritis. The subcutaneous injection formulation of golimumab, Simponi, is already approved for RA, PsA, AS, and ulcerative colitis. Golimumab is a fully human anti–tumor necrosis factor-alpha therapy, and the intravenous formulation is designed for use as a 30-minute infusion.
“In the study for the treatment of active PsA, patients experienced improvement in joint symptoms and inhibition of structural damage. In the study for treatment of active AS, results showed improvement in measures of disease activity,” according to an Oct. 20 announcement from the manufacturer of golimumab, Janssen Biotech.
Read the revised prescribing information for Simponi Aria here.
The U.S. Food and Drug Administration has approved golimumab (Simponi Aria) for use in adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS).
Simponi Aria is an intravenous formulation of golimumab that is already approved for moderate to severe rheumatoid arthritis. The subcutaneous injection formulation of golimumab, Simponi, is already approved for RA, PsA, AS, and ulcerative colitis. Golimumab is a fully human anti–tumor necrosis factor-alpha therapy, and the intravenous formulation is designed for use as a 30-minute infusion.
“In the study for the treatment of active PsA, patients experienced improvement in joint symptoms and inhibition of structural damage. In the study for treatment of active AS, results showed improvement in measures of disease activity,” according to an Oct. 20 announcement from the manufacturer of golimumab, Janssen Biotech.
Read the revised prescribing information for Simponi Aria here.
The U.S. Food and Drug Administration has approved golimumab (Simponi Aria) for use in adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS).
Simponi Aria is an intravenous formulation of golimumab that is already approved for moderate to severe rheumatoid arthritis. The subcutaneous injection formulation of golimumab, Simponi, is already approved for RA, PsA, AS, and ulcerative colitis. Golimumab is a fully human anti–tumor necrosis factor-alpha therapy, and the intravenous formulation is designed for use as a 30-minute infusion.
“In the study for the treatment of active PsA, patients experienced improvement in joint symptoms and inhibition of structural damage. In the study for treatment of active AS, results showed improvement in measures of disease activity,” according to an Oct. 20 announcement from the manufacturer of golimumab, Janssen Biotech.
Read the revised prescribing information for Simponi Aria here.
High ‘nocebo’ effect observed when patients knowingly switch to a biosimilar
Evidence suggests that patients who switch from an originator biologic to open-label treatment with its biosimilar have an increase in subjective but not objective assessments and also discontinue the drug at a high rate, possibly reflecting a “nocebo” response to switching.
If patients’ own negative expectations induced “negative symptoms (hyperalgesia or adverse events) during treatment, the so-called nocebo response,” and was the main contributing factor to the high discontinuation rate, then it will be very important for clinicians to improve communication with patients and their expectations in order to raise acceptance and persistence rates, the investigators said.
Of the 47 patients who discontinued CT-P13, 26 did so because of a perceived lack of effect, 11 because of adverse events, and 10 because of a combination of both of these factors.
Univariate Cox regression analyses showed that shorter infliximab infusion interval, higher 28-joint Disease Activity Scores (DAS28, based on either C-reactive protein [CRP] or erythrocyte sedimentation rate), higher swollen joint count, and patients’ global disease activity score at baseline were associated with CT-P13 discontinuation.
However, patients’ and clinicians’ awareness of the switch could have influenced these factors, the investigators said. For instance, they found that patients who discontinued CT-P13 reported a significant increase in “subjective” assessments such as tender joint count and patient’s global disease activity but not “objective” measures such as swollen joint count or CRP.
While the mean Bath Ankylosing Spondylitis Disease Activity Index score increased from 3.8 to 4.3, the mean DAS28-CRP in rheumatoid arthritis and psoriatic arthritis patients remained stable at 2.2 from baseline to month 6; CRP and anti-infliximab antibody levels also did not change.
“If immunogenicity would have caused CT-P13 discontinuation, we would have expected to find more patients with objectively active disease and/or allergic reactions,” the study authors wrote.
Three of the authors reported receiving speaking and consultancy fees from several pharmaceutical companies. The study was not supported by an outside grant.
Evidence suggests that patients who switch from an originator biologic to open-label treatment with its biosimilar have an increase in subjective but not objective assessments and also discontinue the drug at a high rate, possibly reflecting a “nocebo” response to switching.
If patients’ own negative expectations induced “negative symptoms (hyperalgesia or adverse events) during treatment, the so-called nocebo response,” and was the main contributing factor to the high discontinuation rate, then it will be very important for clinicians to improve communication with patients and their expectations in order to raise acceptance and persistence rates, the investigators said.
Of the 47 patients who discontinued CT-P13, 26 did so because of a perceived lack of effect, 11 because of adverse events, and 10 because of a combination of both of these factors.
Univariate Cox regression analyses showed that shorter infliximab infusion interval, higher 28-joint Disease Activity Scores (DAS28, based on either C-reactive protein [CRP] or erythrocyte sedimentation rate), higher swollen joint count, and patients’ global disease activity score at baseline were associated with CT-P13 discontinuation.
However, patients’ and clinicians’ awareness of the switch could have influenced these factors, the investigators said. For instance, they found that patients who discontinued CT-P13 reported a significant increase in “subjective” assessments such as tender joint count and patient’s global disease activity but not “objective” measures such as swollen joint count or CRP.
While the mean Bath Ankylosing Spondylitis Disease Activity Index score increased from 3.8 to 4.3, the mean DAS28-CRP in rheumatoid arthritis and psoriatic arthritis patients remained stable at 2.2 from baseline to month 6; CRP and anti-infliximab antibody levels also did not change.
“If immunogenicity would have caused CT-P13 discontinuation, we would have expected to find more patients with objectively active disease and/or allergic reactions,” the study authors wrote.
Three of the authors reported receiving speaking and consultancy fees from several pharmaceutical companies. The study was not supported by an outside grant.
Evidence suggests that patients who switch from an originator biologic to open-label treatment with its biosimilar have an increase in subjective but not objective assessments and also discontinue the drug at a high rate, possibly reflecting a “nocebo” response to switching.
If patients’ own negative expectations induced “negative symptoms (hyperalgesia or adverse events) during treatment, the so-called nocebo response,” and was the main contributing factor to the high discontinuation rate, then it will be very important for clinicians to improve communication with patients and their expectations in order to raise acceptance and persistence rates, the investigators said.
Of the 47 patients who discontinued CT-P13, 26 did so because of a perceived lack of effect, 11 because of adverse events, and 10 because of a combination of both of these factors.
Univariate Cox regression analyses showed that shorter infliximab infusion interval, higher 28-joint Disease Activity Scores (DAS28, based on either C-reactive protein [CRP] or erythrocyte sedimentation rate), higher swollen joint count, and patients’ global disease activity score at baseline were associated with CT-P13 discontinuation.
However, patients’ and clinicians’ awareness of the switch could have influenced these factors, the investigators said. For instance, they found that patients who discontinued CT-P13 reported a significant increase in “subjective” assessments such as tender joint count and patient’s global disease activity but not “objective” measures such as swollen joint count or CRP.
While the mean Bath Ankylosing Spondylitis Disease Activity Index score increased from 3.8 to 4.3, the mean DAS28-CRP in rheumatoid arthritis and psoriatic arthritis patients remained stable at 2.2 from baseline to month 6; CRP and anti-infliximab antibody levels also did not change.
“If immunogenicity would have caused CT-P13 discontinuation, we would have expected to find more patients with objectively active disease and/or allergic reactions,” the study authors wrote.
Three of the authors reported receiving speaking and consultancy fees from several pharmaceutical companies. The study was not supported by an outside grant.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: Nearly a quarter of 192 patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, who knowingly switched from originator infliximab to its biosimilar CT-P13 discontinued the biosimilar during 6 months of follow-up.
Data source: A multicenter, prospective cohort study of 192 infliximab-treated patients who transitioned to the infliximab biosimilar CT-P13.
Disclosures: Three of the authors reported receiving speaking and consultancy fees from several pharmaceutical companies. The study was not supported by an outside grant.
Thoracic syndesmophytes common in ankylosing spondylitis
Thoracic syndesmophytes are common in ankylosing spondylitis, even in the absence of lumbar syndesmophytes, according to a study published in the Journal of Rheumatology.
Sovira Tan, PhD, and his colleagues from the National Institute of Arthritis and Musculoskeletal and Skin Diseases wrote that the current standard for radiographic assessment of ankylosing spondylitis scores only the cervical and lumbar spine because of difficulties visualizing the thoracic spine.
“Consequently, the involvement of the thoracic spine with syndesmophytes has not been widely studied,” they wrote. “If syndesmophytes differentially develop in the thoracic spine, exclusion of this large region may affect the validity of spinal fusion biomarker studies.”
In this study, 18 patients with ankylosing spondylitis who did not show complete lumbar fusion on radiographs underwent thoracolumbar CT and lumbar radiography (J Rheumatol. 2017 Oct 1. doi: 10.3899/jrheum.170340). The patients had ankylosing spondylitis for a mean duration of about 19 years, and 11 were treated with tumor necrosis factor inhibitors.
Researchers found syndesmophytes were common overall in intervertebral disc spaces, ranging from 56% to 89%. The rate of syndesmophytes peaked around the thoracolumbar junction, and bridging was both more evident and more extensive in the superior thoracic levels, compared with the lumbar levels.
In all the patients, thoracic syndesmophytes on the CT scan were at least as common as lumbar, and patients with extensive syndesmophytes at multiple lumbar locations typically also had the same in the thoracic region.
However, there were also patients with no, or very few, lumbar syndesmophytes on CT who still had thoracic syndesmophytes, some of which were extensive.
“Importantly, if syndesmophytes were observed on a lumbar radiograph, one could expect there to be syndesmophytes in the thoracic spine, but not the converse,” the authors wrote. “Several patients with normal lumbar radiographs had substantial thoracic syndesmophytes.”
The authors commented that because of its two-dimensional character, radiography has a relatively low sensitivity for detecting syndesmophytes, compared with CT. This could explain why patients with any syndesmophytes in the lumbar region on radiography also had them in the thoracic CT scans.
“By the time syndesmophytes are detectable on lumbar radiographs, structural damage may already have occurred in large portions of the thoracolumbar spine.”
They acknowledged that their method was a research tool and not intended for clinical practice, but also pointed out that CT technology had improved to allow more extensive spine coverage, at an equal effective dose, without compromising scan quality.
The study was supported by the National Institutes of Health. No conflicts of interest disclosures were available.
Thoracic syndesmophytes are common in ankylosing spondylitis, even in the absence of lumbar syndesmophytes, according to a study published in the Journal of Rheumatology.
Sovira Tan, PhD, and his colleagues from the National Institute of Arthritis and Musculoskeletal and Skin Diseases wrote that the current standard for radiographic assessment of ankylosing spondylitis scores only the cervical and lumbar spine because of difficulties visualizing the thoracic spine.
“Consequently, the involvement of the thoracic spine with syndesmophytes has not been widely studied,” they wrote. “If syndesmophytes differentially develop in the thoracic spine, exclusion of this large region may affect the validity of spinal fusion biomarker studies.”
In this study, 18 patients with ankylosing spondylitis who did not show complete lumbar fusion on radiographs underwent thoracolumbar CT and lumbar radiography (J Rheumatol. 2017 Oct 1. doi: 10.3899/jrheum.170340). The patients had ankylosing spondylitis for a mean duration of about 19 years, and 11 were treated with tumor necrosis factor inhibitors.
Researchers found syndesmophytes were common overall in intervertebral disc spaces, ranging from 56% to 89%. The rate of syndesmophytes peaked around the thoracolumbar junction, and bridging was both more evident and more extensive in the superior thoracic levels, compared with the lumbar levels.
In all the patients, thoracic syndesmophytes on the CT scan were at least as common as lumbar, and patients with extensive syndesmophytes at multiple lumbar locations typically also had the same in the thoracic region.
However, there were also patients with no, or very few, lumbar syndesmophytes on CT who still had thoracic syndesmophytes, some of which were extensive.
“Importantly, if syndesmophytes were observed on a lumbar radiograph, one could expect there to be syndesmophytes in the thoracic spine, but not the converse,” the authors wrote. “Several patients with normal lumbar radiographs had substantial thoracic syndesmophytes.”
The authors commented that because of its two-dimensional character, radiography has a relatively low sensitivity for detecting syndesmophytes, compared with CT. This could explain why patients with any syndesmophytes in the lumbar region on radiography also had them in the thoracic CT scans.
“By the time syndesmophytes are detectable on lumbar radiographs, structural damage may already have occurred in large portions of the thoracolumbar spine.”
They acknowledged that their method was a research tool and not intended for clinical practice, but also pointed out that CT technology had improved to allow more extensive spine coverage, at an equal effective dose, without compromising scan quality.
The study was supported by the National Institutes of Health. No conflicts of interest disclosures were available.
Thoracic syndesmophytes are common in ankylosing spondylitis, even in the absence of lumbar syndesmophytes, according to a study published in the Journal of Rheumatology.
Sovira Tan, PhD, and his colleagues from the National Institute of Arthritis and Musculoskeletal and Skin Diseases wrote that the current standard for radiographic assessment of ankylosing spondylitis scores only the cervical and lumbar spine because of difficulties visualizing the thoracic spine.
“Consequently, the involvement of the thoracic spine with syndesmophytes has not been widely studied,” they wrote. “If syndesmophytes differentially develop in the thoracic spine, exclusion of this large region may affect the validity of spinal fusion biomarker studies.”
In this study, 18 patients with ankylosing spondylitis who did not show complete lumbar fusion on radiographs underwent thoracolumbar CT and lumbar radiography (J Rheumatol. 2017 Oct 1. doi: 10.3899/jrheum.170340). The patients had ankylosing spondylitis for a mean duration of about 19 years, and 11 were treated with tumor necrosis factor inhibitors.
Researchers found syndesmophytes were common overall in intervertebral disc spaces, ranging from 56% to 89%. The rate of syndesmophytes peaked around the thoracolumbar junction, and bridging was both more evident and more extensive in the superior thoracic levels, compared with the lumbar levels.
In all the patients, thoracic syndesmophytes on the CT scan were at least as common as lumbar, and patients with extensive syndesmophytes at multiple lumbar locations typically also had the same in the thoracic region.
However, there were also patients with no, or very few, lumbar syndesmophytes on CT who still had thoracic syndesmophytes, some of which were extensive.
“Importantly, if syndesmophytes were observed on a lumbar radiograph, one could expect there to be syndesmophytes in the thoracic spine, but not the converse,” the authors wrote. “Several patients with normal lumbar radiographs had substantial thoracic syndesmophytes.”
The authors commented that because of its two-dimensional character, radiography has a relatively low sensitivity for detecting syndesmophytes, compared with CT. This could explain why patients with any syndesmophytes in the lumbar region on radiography also had them in the thoracic CT scans.
“By the time syndesmophytes are detectable on lumbar radiographs, structural damage may already have occurred in large portions of the thoracolumbar spine.”
They acknowledged that their method was a research tool and not intended for clinical practice, but also pointed out that CT technology had improved to allow more extensive spine coverage, at an equal effective dose, without compromising scan quality.
The study was supported by the National Institutes of Health. No conflicts of interest disclosures were available.
FROM JOURNAL OF RHEUMATOLOGY
Key clinical point:
Major finding: Within individual patients, CT-detected syndesmophytes were either more common in or equally present in thoracic intervertebral disc spaces, compared with lumbar.
Data source: CT and radiography study of 18 patients with ankylosing spondylitis.
Disclosures: The study was supported by the National Institutes of Health. No conflicts of interest disclosures were available.
Launch of adalimumab biosimilar Amjevita postponed
Amgen, maker of the adalimumab biosimilar Amjevita (adalimumab-atto) has reached an agreement with AbbVie, manufacturer of the originator adalimumab Humira, that halts marketing of Amjevita in the United States until 2023 and in Europe until 2018, according to a company statement.
The deal between the two manufacturers settles a patent infringement lawsuit that AbbVie brought against Amgen after it received Food and Drug Administration approval in September 2016 for seven of Humira’s nine indications: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, and polyarticular juvenile idiopathic arthritis. Amjevita is not approved for two of Humira’s indications, hidradenitis suppurativa and uveitis.
Amgen said in its statement that AbbVie will grant patent licenses for the use and sale of Amjevita worldwide, on a country-by-country basis, with current expectations that marketing will begin in Europe on Oct. 16, 2018, and in the United States on Jan. 31, 2023. Amjevita is named Amgevita in Europe.
Amgen, maker of the adalimumab biosimilar Amjevita (adalimumab-atto) has reached an agreement with AbbVie, manufacturer of the originator adalimumab Humira, that halts marketing of Amjevita in the United States until 2023 and in Europe until 2018, according to a company statement.
The deal between the two manufacturers settles a patent infringement lawsuit that AbbVie brought against Amgen after it received Food and Drug Administration approval in September 2016 for seven of Humira’s nine indications: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, and polyarticular juvenile idiopathic arthritis. Amjevita is not approved for two of Humira’s indications, hidradenitis suppurativa and uveitis.
Amgen said in its statement that AbbVie will grant patent licenses for the use and sale of Amjevita worldwide, on a country-by-country basis, with current expectations that marketing will begin in Europe on Oct. 16, 2018, and in the United States on Jan. 31, 2023. Amjevita is named Amgevita in Europe.
Amgen, maker of the adalimumab biosimilar Amjevita (adalimumab-atto) has reached an agreement with AbbVie, manufacturer of the originator adalimumab Humira, that halts marketing of Amjevita in the United States until 2023 and in Europe until 2018, according to a company statement.
The deal between the two manufacturers settles a patent infringement lawsuit that AbbVie brought against Amgen after it received Food and Drug Administration approval in September 2016 for seven of Humira’s nine indications: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, and polyarticular juvenile idiopathic arthritis. Amjevita is not approved for two of Humira’s indications, hidradenitis suppurativa and uveitis.
Amgen said in its statement that AbbVie will grant patent licenses for the use and sale of Amjevita worldwide, on a country-by-country basis, with current expectations that marketing will begin in Europe on Oct. 16, 2018, and in the United States on Jan. 31, 2023. Amjevita is named Amgevita in Europe.
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