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Role of musculoskeletal ultrasound expands in rheumatic diseases
MAUI, HAWAII – Recent studies highlight novel applications of musculoskeletal ultrasound across a broad spectrum of rheumatic diseases beyond the imaging method’s well-established role in diagnosis and follow-up of patients with rheumatoid arthritis, Alvin F. Wells, MD, PhD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited recently published evidence in support of his contention:
Systemic lupus erythematosus
Portuguese investigators reported that 77% of their study participants with asymptomatic systemic lupus erythematosus (SLE) – that is, no arthralgia or musculoskeletal signs or symptoms on physical examination – demonstrated gray-scale ultrasound evidence of grade 1 or greater synovial hypertrophy of joints in the hands and/or wrists on a semiquantitative 0-3 scale. So did 100% of patients with symptomatic SLE in this small study, in which physicians evaluated 22 joints per person.
Moreover, grade 1 or greater intra-articular power Doppler changes were also detected in one-fifth of the asymptomatic patients and 83% of those with symptomatic SLE. What the researchers considered persuasive ultrasound evidence of synovitis – grade 2 or 3 synovial hypertrophy or at least grade 1 power Doppler findings – was noted in 23% of the asymptomatic SLE patients, 83% of those who were symptomatic, and none of the healthy controls.
The investigators concluded that asymptomatic patients with SLE may present with subclinical joint inflammation that often goes undetected by physical examination and x-ray. They added that ultrasound with power Doppler may be important in disease evaluation and therapeutic monitoring in patients with lupus (Lupus Sci Med. 2017 Jan 19;4[1]:e000184).
For Dr. Wells, the take-home message was clear: “Don’t overlook the hands.”
“In my lupus patients, sure, I look at the hips, making sure there are no subtle signs of osteonecrosis, but I think we often forget to look at the hands. We’re looking at the hair, looking at the mouth, we’re worried about the lungs. But I think we often overlook the synovitis. These patients are going to the ER because they’re having pain in their hands, and they’re getting told, ‘This is fibromyalgia, go back and see your rheumatologist.’ So it’s something to think about: When you’ve got a patient with active lupus, ultrasound may have a role to play,” according to Dr. Wells.
The big unanswered question is whether early aggressive treatment in SLE patients with these synovial abnormalities – that is, a treat-to-target, ultrasound-guided strategy – can limit erosive changes, avoid disease progression, and improve functional outcomes, as is now known to be the case in RA. Long-term studies will be required to find out, he noted.
Ultrasound of parotid glands in suspected Sjögren’s syndrome is biopsy sparing
Members of the European League Against Rheumatism Ultrasound Primary Sjögren’s Syndrome Study Group recently reported that in a prospective study of 103 consecutive outpatients with clinically suspected primary Sjögren’s syndrome, a positive ultrasound examination of the major salivary glands in combination with the presence of anti-SSA/Ro antibodies was highly predictive of positive parotid and labial gland biopsies. Indeed, a positive ultrasound plus anti-SSA/Ro antibodies showed a high predictive value for Sjögren’s syndrome regardless of whether the classification was based upon American College of Rheumatology, American European Consensus Group, or ACR-EULAR criteria (Ann Rheum Dis. 2017;76[11]:1883-9).
“Ophthalmologists, dentists, and primary care physicians frequently refer patients with dry eyes and dry mouth to us to sort out whether they have Sjögren’s syndrome. The data show now that with a positive salivary gland ultrasound score and a positive anti-SSA/Ro antibody test you can avoid the biopsies,” the rheumatologist said.
That’s a fine thing for patients because these biopsies often result in residual numbness and tingling, he added.
Dr. Wells noted that a multicenter European group recently fine-tuned the criteria for an abnormal salivary gland ultrasound score. They identified echogenicity and homogeneity as the two most reliable items on the score. They also reported that the mean time it took five ultrasonographers to perform salivary gland assessments was reasonable at 11-27 minutes (RMD Open. 2017 Jun 9;3[1]:e000364).
“You can do this essentially in an office visit. The changes in the salivary glands are pathognomonic for Sjögren’s – you won’t get it confused with a neoplasm. I schedule these patients for a 15-minute time slot, and based upon the ultrasound and whether they’re positive or negative for anti-SSA/Ro antibodies I can make some decisions from there,” Dr. Wells explained.
He described what to look for on ultrasound: “A normal parotid looks like a homogeneous gray sponge on ultrasound. In Sjögren’s syndrome, you see icepicklike holes in the sponge. And there’s thickening of the intima, so you see blunting of the arterial wave on pulse wave.”
Implications of ultrasound enthesitis in early spondyloarthritis
French rheumatologists reported on the implications of an ultrasound peripheral enthesis assessment in 402 patients with early axial spondyloarthritis in the French DESIR cohort. The ultrasound evaluation covered the lateral epicondyles, Achilles tendon, and superior and inferior patellar ligament entheses. The results were summed up in ultrasound structural and power Doppler scores. In addition, the investigators obtained spine and sacroiliac joint MRI scans and spine x-rays, all scored centrally.
It turned out that ultrasound abnormalities weren’t useful in monitoring axial spondyloarthritis clinical disease activity as reflected in Bath Ankylosing Spondylitis Disease Activity Index scores, nor were the ultrasound structural and power Doppler scores associated with MRI spine inflammatory lesions or sacroiliitis. However, ultrasound enthesophytes were strongly associated with axial syndesmophytes, suggesting that these ultrasound abnormalities might be a marker of disease severity in axial spondyloarthritis (RMD Open. 2017 Sep 7;3[2]:e000482).
“Whether or not by inhibiting these peripheral enthesophytes you’ll ultimately inhibit further enthesophytes or syndesmophytes from forming is yet to be seen,” Dr. Wells cautioned.
He added, however, that a recent short-term, randomized, placebo-controlled trial in 185 patients with nonradiographic axial spondyloarthritis holds hope in that regard. Investigators in the ongoing multicenter EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic Spondyloarthritis) trial reported that treatment with etanercept was associated with a significantly greater reduction in erosions, an increase in backfill, and improved clinical outcomes, compared with placebo, as assessed by MRIs obtained at baseline and 12 weeks.
The investigators viewed these findings as consistent with an early reparative response to the anti–tumor necrosis factor agent, although they noted that understanding of the biologic agent’s true impact on disease progression awaits longer-term follow-up in the 104-week study (Ann Rheum Dis. 2018 Jan;77[1]:78-84).
Dr. Wells reported serving as a consultant to more than half a dozen pharmaceutical companies and receiving research funding from Abbott, Celgene, and UCB.
MAUI, HAWAII – Recent studies highlight novel applications of musculoskeletal ultrasound across a broad spectrum of rheumatic diseases beyond the imaging method’s well-established role in diagnosis and follow-up of patients with rheumatoid arthritis, Alvin F. Wells, MD, PhD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited recently published evidence in support of his contention:
Systemic lupus erythematosus
Portuguese investigators reported that 77% of their study participants with asymptomatic systemic lupus erythematosus (SLE) – that is, no arthralgia or musculoskeletal signs or symptoms on physical examination – demonstrated gray-scale ultrasound evidence of grade 1 or greater synovial hypertrophy of joints in the hands and/or wrists on a semiquantitative 0-3 scale. So did 100% of patients with symptomatic SLE in this small study, in which physicians evaluated 22 joints per person.
Moreover, grade 1 or greater intra-articular power Doppler changes were also detected in one-fifth of the asymptomatic patients and 83% of those with symptomatic SLE. What the researchers considered persuasive ultrasound evidence of synovitis – grade 2 or 3 synovial hypertrophy or at least grade 1 power Doppler findings – was noted in 23% of the asymptomatic SLE patients, 83% of those who were symptomatic, and none of the healthy controls.
The investigators concluded that asymptomatic patients with SLE may present with subclinical joint inflammation that often goes undetected by physical examination and x-ray. They added that ultrasound with power Doppler may be important in disease evaluation and therapeutic monitoring in patients with lupus (Lupus Sci Med. 2017 Jan 19;4[1]:e000184).
For Dr. Wells, the take-home message was clear: “Don’t overlook the hands.”
“In my lupus patients, sure, I look at the hips, making sure there are no subtle signs of osteonecrosis, but I think we often forget to look at the hands. We’re looking at the hair, looking at the mouth, we’re worried about the lungs. But I think we often overlook the synovitis. These patients are going to the ER because they’re having pain in their hands, and they’re getting told, ‘This is fibromyalgia, go back and see your rheumatologist.’ So it’s something to think about: When you’ve got a patient with active lupus, ultrasound may have a role to play,” according to Dr. Wells.
The big unanswered question is whether early aggressive treatment in SLE patients with these synovial abnormalities – that is, a treat-to-target, ultrasound-guided strategy – can limit erosive changes, avoid disease progression, and improve functional outcomes, as is now known to be the case in RA. Long-term studies will be required to find out, he noted.
Ultrasound of parotid glands in suspected Sjögren’s syndrome is biopsy sparing
Members of the European League Against Rheumatism Ultrasound Primary Sjögren’s Syndrome Study Group recently reported that in a prospective study of 103 consecutive outpatients with clinically suspected primary Sjögren’s syndrome, a positive ultrasound examination of the major salivary glands in combination with the presence of anti-SSA/Ro antibodies was highly predictive of positive parotid and labial gland biopsies. Indeed, a positive ultrasound plus anti-SSA/Ro antibodies showed a high predictive value for Sjögren’s syndrome regardless of whether the classification was based upon American College of Rheumatology, American European Consensus Group, or ACR-EULAR criteria (Ann Rheum Dis. 2017;76[11]:1883-9).
“Ophthalmologists, dentists, and primary care physicians frequently refer patients with dry eyes and dry mouth to us to sort out whether they have Sjögren’s syndrome. The data show now that with a positive salivary gland ultrasound score and a positive anti-SSA/Ro antibody test you can avoid the biopsies,” the rheumatologist said.
That’s a fine thing for patients because these biopsies often result in residual numbness and tingling, he added.
Dr. Wells noted that a multicenter European group recently fine-tuned the criteria for an abnormal salivary gland ultrasound score. They identified echogenicity and homogeneity as the two most reliable items on the score. They also reported that the mean time it took five ultrasonographers to perform salivary gland assessments was reasonable at 11-27 minutes (RMD Open. 2017 Jun 9;3[1]:e000364).
“You can do this essentially in an office visit. The changes in the salivary glands are pathognomonic for Sjögren’s – you won’t get it confused with a neoplasm. I schedule these patients for a 15-minute time slot, and based upon the ultrasound and whether they’re positive or negative for anti-SSA/Ro antibodies I can make some decisions from there,” Dr. Wells explained.
He described what to look for on ultrasound: “A normal parotid looks like a homogeneous gray sponge on ultrasound. In Sjögren’s syndrome, you see icepicklike holes in the sponge. And there’s thickening of the intima, so you see blunting of the arterial wave on pulse wave.”
Implications of ultrasound enthesitis in early spondyloarthritis
French rheumatologists reported on the implications of an ultrasound peripheral enthesis assessment in 402 patients with early axial spondyloarthritis in the French DESIR cohort. The ultrasound evaluation covered the lateral epicondyles, Achilles tendon, and superior and inferior patellar ligament entheses. The results were summed up in ultrasound structural and power Doppler scores. In addition, the investigators obtained spine and sacroiliac joint MRI scans and spine x-rays, all scored centrally.
It turned out that ultrasound abnormalities weren’t useful in monitoring axial spondyloarthritis clinical disease activity as reflected in Bath Ankylosing Spondylitis Disease Activity Index scores, nor were the ultrasound structural and power Doppler scores associated with MRI spine inflammatory lesions or sacroiliitis. However, ultrasound enthesophytes were strongly associated with axial syndesmophytes, suggesting that these ultrasound abnormalities might be a marker of disease severity in axial spondyloarthritis (RMD Open. 2017 Sep 7;3[2]:e000482).
“Whether or not by inhibiting these peripheral enthesophytes you’ll ultimately inhibit further enthesophytes or syndesmophytes from forming is yet to be seen,” Dr. Wells cautioned.
He added, however, that a recent short-term, randomized, placebo-controlled trial in 185 patients with nonradiographic axial spondyloarthritis holds hope in that regard. Investigators in the ongoing multicenter EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic Spondyloarthritis) trial reported that treatment with etanercept was associated with a significantly greater reduction in erosions, an increase in backfill, and improved clinical outcomes, compared with placebo, as assessed by MRIs obtained at baseline and 12 weeks.
The investigators viewed these findings as consistent with an early reparative response to the anti–tumor necrosis factor agent, although they noted that understanding of the biologic agent’s true impact on disease progression awaits longer-term follow-up in the 104-week study (Ann Rheum Dis. 2018 Jan;77[1]:78-84).
Dr. Wells reported serving as a consultant to more than half a dozen pharmaceutical companies and receiving research funding from Abbott, Celgene, and UCB.
MAUI, HAWAII – Recent studies highlight novel applications of musculoskeletal ultrasound across a broad spectrum of rheumatic diseases beyond the imaging method’s well-established role in diagnosis and follow-up of patients with rheumatoid arthritis, Alvin F. Wells, MD, PhD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited recently published evidence in support of his contention:
Systemic lupus erythematosus
Portuguese investigators reported that 77% of their study participants with asymptomatic systemic lupus erythematosus (SLE) – that is, no arthralgia or musculoskeletal signs or symptoms on physical examination – demonstrated gray-scale ultrasound evidence of grade 1 or greater synovial hypertrophy of joints in the hands and/or wrists on a semiquantitative 0-3 scale. So did 100% of patients with symptomatic SLE in this small study, in which physicians evaluated 22 joints per person.
Moreover, grade 1 or greater intra-articular power Doppler changes were also detected in one-fifth of the asymptomatic patients and 83% of those with symptomatic SLE. What the researchers considered persuasive ultrasound evidence of synovitis – grade 2 or 3 synovial hypertrophy or at least grade 1 power Doppler findings – was noted in 23% of the asymptomatic SLE patients, 83% of those who were symptomatic, and none of the healthy controls.
The investigators concluded that asymptomatic patients with SLE may present with subclinical joint inflammation that often goes undetected by physical examination and x-ray. They added that ultrasound with power Doppler may be important in disease evaluation and therapeutic monitoring in patients with lupus (Lupus Sci Med. 2017 Jan 19;4[1]:e000184).
For Dr. Wells, the take-home message was clear: “Don’t overlook the hands.”
“In my lupus patients, sure, I look at the hips, making sure there are no subtle signs of osteonecrosis, but I think we often forget to look at the hands. We’re looking at the hair, looking at the mouth, we’re worried about the lungs. But I think we often overlook the synovitis. These patients are going to the ER because they’re having pain in their hands, and they’re getting told, ‘This is fibromyalgia, go back and see your rheumatologist.’ So it’s something to think about: When you’ve got a patient with active lupus, ultrasound may have a role to play,” according to Dr. Wells.
The big unanswered question is whether early aggressive treatment in SLE patients with these synovial abnormalities – that is, a treat-to-target, ultrasound-guided strategy – can limit erosive changes, avoid disease progression, and improve functional outcomes, as is now known to be the case in RA. Long-term studies will be required to find out, he noted.
Ultrasound of parotid glands in suspected Sjögren’s syndrome is biopsy sparing
Members of the European League Against Rheumatism Ultrasound Primary Sjögren’s Syndrome Study Group recently reported that in a prospective study of 103 consecutive outpatients with clinically suspected primary Sjögren’s syndrome, a positive ultrasound examination of the major salivary glands in combination with the presence of anti-SSA/Ro antibodies was highly predictive of positive parotid and labial gland biopsies. Indeed, a positive ultrasound plus anti-SSA/Ro antibodies showed a high predictive value for Sjögren’s syndrome regardless of whether the classification was based upon American College of Rheumatology, American European Consensus Group, or ACR-EULAR criteria (Ann Rheum Dis. 2017;76[11]:1883-9).
“Ophthalmologists, dentists, and primary care physicians frequently refer patients with dry eyes and dry mouth to us to sort out whether they have Sjögren’s syndrome. The data show now that with a positive salivary gland ultrasound score and a positive anti-SSA/Ro antibody test you can avoid the biopsies,” the rheumatologist said.
That’s a fine thing for patients because these biopsies often result in residual numbness and tingling, he added.
Dr. Wells noted that a multicenter European group recently fine-tuned the criteria for an abnormal salivary gland ultrasound score. They identified echogenicity and homogeneity as the two most reliable items on the score. They also reported that the mean time it took five ultrasonographers to perform salivary gland assessments was reasonable at 11-27 minutes (RMD Open. 2017 Jun 9;3[1]:e000364).
“You can do this essentially in an office visit. The changes in the salivary glands are pathognomonic for Sjögren’s – you won’t get it confused with a neoplasm. I schedule these patients for a 15-minute time slot, and based upon the ultrasound and whether they’re positive or negative for anti-SSA/Ro antibodies I can make some decisions from there,” Dr. Wells explained.
He described what to look for on ultrasound: “A normal parotid looks like a homogeneous gray sponge on ultrasound. In Sjögren’s syndrome, you see icepicklike holes in the sponge. And there’s thickening of the intima, so you see blunting of the arterial wave on pulse wave.”
Implications of ultrasound enthesitis in early spondyloarthritis
French rheumatologists reported on the implications of an ultrasound peripheral enthesis assessment in 402 patients with early axial spondyloarthritis in the French DESIR cohort. The ultrasound evaluation covered the lateral epicondyles, Achilles tendon, and superior and inferior patellar ligament entheses. The results were summed up in ultrasound structural and power Doppler scores. In addition, the investigators obtained spine and sacroiliac joint MRI scans and spine x-rays, all scored centrally.
It turned out that ultrasound abnormalities weren’t useful in monitoring axial spondyloarthritis clinical disease activity as reflected in Bath Ankylosing Spondylitis Disease Activity Index scores, nor were the ultrasound structural and power Doppler scores associated with MRI spine inflammatory lesions or sacroiliitis. However, ultrasound enthesophytes were strongly associated with axial syndesmophytes, suggesting that these ultrasound abnormalities might be a marker of disease severity in axial spondyloarthritis (RMD Open. 2017 Sep 7;3[2]:e000482).
“Whether or not by inhibiting these peripheral enthesophytes you’ll ultimately inhibit further enthesophytes or syndesmophytes from forming is yet to be seen,” Dr. Wells cautioned.
He added, however, that a recent short-term, randomized, placebo-controlled trial in 185 patients with nonradiographic axial spondyloarthritis holds hope in that regard. Investigators in the ongoing multicenter EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic Spondyloarthritis) trial reported that treatment with etanercept was associated with a significantly greater reduction in erosions, an increase in backfill, and improved clinical outcomes, compared with placebo, as assessed by MRIs obtained at baseline and 12 weeks.
The investigators viewed these findings as consistent with an early reparative response to the anti–tumor necrosis factor agent, although they noted that understanding of the biologic agent’s true impact on disease progression awaits longer-term follow-up in the 104-week study (Ann Rheum Dis. 2018 Jan;77[1]:78-84).
Dr. Wells reported serving as a consultant to more than half a dozen pharmaceutical companies and receiving research funding from Abbott, Celgene, and UCB.
EXPERT ANALYSIS FROM RWCS 2018
TNF inhibitors curb spinal x-ray progression in ankylosing spondylitis
MAUI, HAWAII – How long do patients with ankylosing spondylitis need to be on a tumor necrosis factor (TNF) blocker in order to experience clinically meaningful inhibition of spinal x-ray progression?
At least 2 years, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited a study by the rheumatologists of the Swiss Clinical Quality Management Program which he considers one of the recent highlights in rheumatologic imaging.
The mean increase in mSASSS was 0.9 units in 2 years. Prior use of a TNF inhibitor reduced the likelihood of progression by 50% in a multivariate analysis, observed Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is also in private practice in Santa Monica, Calif.
Responders to anti-TNF therapy as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or less at the beginning of a 2-year radiographic interval had a mean mSASSS progression of just 0.31 units in the next 2 years, compared with a 1.45-unit increase in nonresponders to anti-TNF therapy with an ASDAS score above 2.1.
Moreover, patients on anti-TNF therapy who achieved inactive disease status as defined by an ASDAS of 1.3 or less at the beginning of the next 2-year radiographic interval experienced essentially no radiographic progression during that interval, with a mean mSASSS increase of just 0.01 units as compared with a 0.52-unit increase in those with an ASDAS of 1.3-2.1. The inference, according to the investigators, is that the reduction in spinal x-ray progression associated with TNF inhibitor (TNFi) therapy was mediated by the biologic therapy’s inhibitory effect on disease activity.
“We present important clues concerning the period of time needed before the inhibitory effects can be objectified: around 2 years of continuous TNFi use, as there was no impact of TNFi treatment during a 2-year radiographic interval, while there was an effect if the treatment was started before this interval. ... Our study suggests that [an ASDAS of 1.3 or less] might be an adequate target, if the goal of treatment is inhibition of further spinal radiographic damage in addition to control of signs and symptoms, ” according to the investigators (Ann Rheum Dis. 2018 Jan;77[1]:63-9).
Dr. Troum reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.
MAUI, HAWAII – How long do patients with ankylosing spondylitis need to be on a tumor necrosis factor (TNF) blocker in order to experience clinically meaningful inhibition of spinal x-ray progression?
At least 2 years, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited a study by the rheumatologists of the Swiss Clinical Quality Management Program which he considers one of the recent highlights in rheumatologic imaging.
The mean increase in mSASSS was 0.9 units in 2 years. Prior use of a TNF inhibitor reduced the likelihood of progression by 50% in a multivariate analysis, observed Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is also in private practice in Santa Monica, Calif.
Responders to anti-TNF therapy as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or less at the beginning of a 2-year radiographic interval had a mean mSASSS progression of just 0.31 units in the next 2 years, compared with a 1.45-unit increase in nonresponders to anti-TNF therapy with an ASDAS score above 2.1.
Moreover, patients on anti-TNF therapy who achieved inactive disease status as defined by an ASDAS of 1.3 or less at the beginning of the next 2-year radiographic interval experienced essentially no radiographic progression during that interval, with a mean mSASSS increase of just 0.01 units as compared with a 0.52-unit increase in those with an ASDAS of 1.3-2.1. The inference, according to the investigators, is that the reduction in spinal x-ray progression associated with TNF inhibitor (TNFi) therapy was mediated by the biologic therapy’s inhibitory effect on disease activity.
“We present important clues concerning the period of time needed before the inhibitory effects can be objectified: around 2 years of continuous TNFi use, as there was no impact of TNFi treatment during a 2-year radiographic interval, while there was an effect if the treatment was started before this interval. ... Our study suggests that [an ASDAS of 1.3 or less] might be an adequate target, if the goal of treatment is inhibition of further spinal radiographic damage in addition to control of signs and symptoms, ” according to the investigators (Ann Rheum Dis. 2018 Jan;77[1]:63-9).
Dr. Troum reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.
MAUI, HAWAII – How long do patients with ankylosing spondylitis need to be on a tumor necrosis factor (TNF) blocker in order to experience clinically meaningful inhibition of spinal x-ray progression?
At least 2 years, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited a study by the rheumatologists of the Swiss Clinical Quality Management Program which he considers one of the recent highlights in rheumatologic imaging.
The mean increase in mSASSS was 0.9 units in 2 years. Prior use of a TNF inhibitor reduced the likelihood of progression by 50% in a multivariate analysis, observed Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is also in private practice in Santa Monica, Calif.
Responders to anti-TNF therapy as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or less at the beginning of a 2-year radiographic interval had a mean mSASSS progression of just 0.31 units in the next 2 years, compared with a 1.45-unit increase in nonresponders to anti-TNF therapy with an ASDAS score above 2.1.
Moreover, patients on anti-TNF therapy who achieved inactive disease status as defined by an ASDAS of 1.3 or less at the beginning of the next 2-year radiographic interval experienced essentially no radiographic progression during that interval, with a mean mSASSS increase of just 0.01 units as compared with a 0.52-unit increase in those with an ASDAS of 1.3-2.1. The inference, according to the investigators, is that the reduction in spinal x-ray progression associated with TNF inhibitor (TNFi) therapy was mediated by the biologic therapy’s inhibitory effect on disease activity.
“We present important clues concerning the period of time needed before the inhibitory effects can be objectified: around 2 years of continuous TNFi use, as there was no impact of TNFi treatment during a 2-year radiographic interval, while there was an effect if the treatment was started before this interval. ... Our study suggests that [an ASDAS of 1.3 or less] might be an adequate target, if the goal of treatment is inhibition of further spinal radiographic damage in addition to control of signs and symptoms, ” according to the investigators (Ann Rheum Dis. 2018 Jan;77[1]:63-9).
Dr. Troum reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2018
ACR sounds more welcoming tone in new biosimilars position paper
The American College of Rheumatology has shifted from a more cautious stance toward the use of biosimilars in clinical practice to now recommend in a new position statement that health care providers incorporate biosimilars, where appropriate, into treatment regimens for their patients living with rheumatic diseases.
“Now that biosimilars have been used successfully in Europe, with rigorously acquired data supporting their broader use, and , S. Louis Bridges Jr., MD, PhD, chair of the ACR Committee on Research, wrote with seven other authors of the position statement in Arthritis & Rheumatology.
The ACR position statement addresses the issues of immunogenicity, extrapolation of indications, interchangeability, substitution, switching, and cost surrounding biosimilars.
The position statement’s authors said they expect switching and nonmedical substitution to become as common in the United States as it is in the rest of the world. They do not anticipate efficacy and safety issues for biosimilars based on available data regarding switching between reference products and biosimilars and their understanding of product drift.
“However, we encourage vigorous postmarketing surveillance of both biosimilars and their reference products as we enter the era where patients may undergo multiple switches as a result of insurance company and [pharmacy benefits manager] formulary preferences,” they said.
Immunogenicity
Concerns about immunogenicity for biosimilars approved in the United States have mostly been well addressed through studies showing similar frequencies of binding and neutralizing antidrug antibodies (ADA) in biosimilars and their reference products. Furthermore, no safety signals between biosimilars and their reference products have been observed that suggest a differential effect of ADA on efficacy, safety, or patient outcomes, the authors said. But they noted that “if immunogenicity findings are to be extrapolated from one disease to additional indications, the subjects being studied should be those most likely to develop ADA, such as subjects not receiving concomitant immunosuppressive medications.” The results of comparative immunogenicity studies carried out to date also indicate that “a patient who develops ADA to a reference drug with resultant loss of clinical response should not be switched to its biosimilar.”
Again, the authors said postmarketing pharmacovigilance using observational registry data would be critical to assessing the effect of switching on immunogenicity.
Extrapolation of indications
The extrapolation of biosimilars to reference product indications for which the biosimilar was not assessed in clinical trials continues to “be an area of uneasiness” among clinicians “who are surprised to find” that a biosimilar can be approved for inflammatory bowel disease in the absence of clinical trials in the relevant patient populations, the authors said. In geographic areas where it is not mandatory to use biosimilars, this lack of confidence in extrapolation of indications may limit their acceptance, the authors wrote, but data from studies such as NOR-SWITCH and DANBIO have provided reassuring evidence to support regulated extrapolation of indication for biosimilars.
However, since extrapolation of indications also applies to pediatric patients who often metabolize drugs faster than adults, the position paper says that “it may be important” to conduct pharmacodynamic and pharmacokinetic studies in children as well as postmarketing surveillance “since potential immunogenicity may be of particular importance in these younger patients with chronic diseases who might encounter several biological agents during their lifetime.”
Substitution, interchangeability, and switching
The “interchangeability” regulatory pathway in the United States that would allow substitution at the point of dispensing has not been finalized, but most states have enacted, or are in the process of enacting, legislation to regulate the practice, the statement says.
While substitution describes a change made by someone other than the prescriber, the authors note that switching defines the “intentional change initiated by a health care provider in partnership with the patient” for economic or medical reasons. Switching has been studied most often in open-label extension studies of biosimilar clinic trials and has shown no loss of efficacy or increase in adverse events.
Dr. Fleischmann contended that substitution, extrapolation, and interchangeability of biosimilars in clinical practice remain gray areas. For example, in a clinical trial, patients switching from a reference product to a biosimilar may show equivalency of clinical response and adverse events. “But as rheumatologists, we don’t treat groups of patients; we treat individual patients and here the results may be different,” he wrote in Arthritis & Rheumatology.
While the white paper appropriately points out that interchangeability among multiple biosimilars is a question that should be answered in postmarketing registries, Dr. Fleischmann noted that no interchangeability study has been reported, even though the FDA has issued guidance on how a study should be done.
“Although interchangeability may be safe and effective in many patients, until the results of such a study are available and properly analyzed, it is only conjecture that interchangeability is appropriate and safe,” he said.
Costs
The white paper acknowledged that the “only anticipated advantage” of a biosimilar over its reference product was lower cost, since both drugs should be therapeutically equivalent. “The degree to which the availability of biosimilars in the U.S. will drive down the cost of biologic therapy, and who will benefit from any cost reductions remains to be seen,” the authors wrote.
“To incentivize the use of biosimilars,” the authors suggested that “commercial and government insurance programs could harmonize drug prices with patients’ out-of-pocket costs and provider reimbursement. Currently, however, patients with commercial insurance are likely to have similar copayments for both biosimilars and originator biologics because of [pharmacy benefits manager]– or plan-mandated patient cost sharing. Also, patients’ out-of-pocket costs for biosimilars in the Medicare Part D (self-administered drug) program likely will be higher than for originator biologics because of a flaw that maintains, rather than reduces, biosimilar patient cost sharing in the coverage gap (also known as the “donut hole”) until 2020.”
It is not at all clear that a biosimilar would be cheaper for the individual patient, Dr. Fleischmann said. “It may be cheaper to the pharmacy benefit management firm, but this may not really help patient access to these medications. It is also not clear that nonmedical substitution will be effective in every patient nor has it been demonstrated that extrapolation is effective,” he wrote.
No disclosures were listed for the authors of the position statement. Dr. Fleischmann is a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Sanofi Aventis, and UCB.
SOURCES: Bridges S et al. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40388; and Fleischmann R. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40402
The American College of Rheumatology has shifted from a more cautious stance toward the use of biosimilars in clinical practice to now recommend in a new position statement that health care providers incorporate biosimilars, where appropriate, into treatment regimens for their patients living with rheumatic diseases.
“Now that biosimilars have been used successfully in Europe, with rigorously acquired data supporting their broader use, and , S. Louis Bridges Jr., MD, PhD, chair of the ACR Committee on Research, wrote with seven other authors of the position statement in Arthritis & Rheumatology.
The ACR position statement addresses the issues of immunogenicity, extrapolation of indications, interchangeability, substitution, switching, and cost surrounding biosimilars.
The position statement’s authors said they expect switching and nonmedical substitution to become as common in the United States as it is in the rest of the world. They do not anticipate efficacy and safety issues for biosimilars based on available data regarding switching between reference products and biosimilars and their understanding of product drift.
“However, we encourage vigorous postmarketing surveillance of both biosimilars and their reference products as we enter the era where patients may undergo multiple switches as a result of insurance company and [pharmacy benefits manager] formulary preferences,” they said.
Immunogenicity
Concerns about immunogenicity for biosimilars approved in the United States have mostly been well addressed through studies showing similar frequencies of binding and neutralizing antidrug antibodies (ADA) in biosimilars and their reference products. Furthermore, no safety signals between biosimilars and their reference products have been observed that suggest a differential effect of ADA on efficacy, safety, or patient outcomes, the authors said. But they noted that “if immunogenicity findings are to be extrapolated from one disease to additional indications, the subjects being studied should be those most likely to develop ADA, such as subjects not receiving concomitant immunosuppressive medications.” The results of comparative immunogenicity studies carried out to date also indicate that “a patient who develops ADA to a reference drug with resultant loss of clinical response should not be switched to its biosimilar.”
Again, the authors said postmarketing pharmacovigilance using observational registry data would be critical to assessing the effect of switching on immunogenicity.
Extrapolation of indications
The extrapolation of biosimilars to reference product indications for which the biosimilar was not assessed in clinical trials continues to “be an area of uneasiness” among clinicians “who are surprised to find” that a biosimilar can be approved for inflammatory bowel disease in the absence of clinical trials in the relevant patient populations, the authors said. In geographic areas where it is not mandatory to use biosimilars, this lack of confidence in extrapolation of indications may limit their acceptance, the authors wrote, but data from studies such as NOR-SWITCH and DANBIO have provided reassuring evidence to support regulated extrapolation of indication for biosimilars.
However, since extrapolation of indications also applies to pediatric patients who often metabolize drugs faster than adults, the position paper says that “it may be important” to conduct pharmacodynamic and pharmacokinetic studies in children as well as postmarketing surveillance “since potential immunogenicity may be of particular importance in these younger patients with chronic diseases who might encounter several biological agents during their lifetime.”
Substitution, interchangeability, and switching
The “interchangeability” regulatory pathway in the United States that would allow substitution at the point of dispensing has not been finalized, but most states have enacted, or are in the process of enacting, legislation to regulate the practice, the statement says.
While substitution describes a change made by someone other than the prescriber, the authors note that switching defines the “intentional change initiated by a health care provider in partnership with the patient” for economic or medical reasons. Switching has been studied most often in open-label extension studies of biosimilar clinic trials and has shown no loss of efficacy or increase in adverse events.
Dr. Fleischmann contended that substitution, extrapolation, and interchangeability of biosimilars in clinical practice remain gray areas. For example, in a clinical trial, patients switching from a reference product to a biosimilar may show equivalency of clinical response and adverse events. “But as rheumatologists, we don’t treat groups of patients; we treat individual patients and here the results may be different,” he wrote in Arthritis & Rheumatology.
While the white paper appropriately points out that interchangeability among multiple biosimilars is a question that should be answered in postmarketing registries, Dr. Fleischmann noted that no interchangeability study has been reported, even though the FDA has issued guidance on how a study should be done.
“Although interchangeability may be safe and effective in many patients, until the results of such a study are available and properly analyzed, it is only conjecture that interchangeability is appropriate and safe,” he said.
Costs
The white paper acknowledged that the “only anticipated advantage” of a biosimilar over its reference product was lower cost, since both drugs should be therapeutically equivalent. “The degree to which the availability of biosimilars in the U.S. will drive down the cost of biologic therapy, and who will benefit from any cost reductions remains to be seen,” the authors wrote.
“To incentivize the use of biosimilars,” the authors suggested that “commercial and government insurance programs could harmonize drug prices with patients’ out-of-pocket costs and provider reimbursement. Currently, however, patients with commercial insurance are likely to have similar copayments for both biosimilars and originator biologics because of [pharmacy benefits manager]– or plan-mandated patient cost sharing. Also, patients’ out-of-pocket costs for biosimilars in the Medicare Part D (self-administered drug) program likely will be higher than for originator biologics because of a flaw that maintains, rather than reduces, biosimilar patient cost sharing in the coverage gap (also known as the “donut hole”) until 2020.”
It is not at all clear that a biosimilar would be cheaper for the individual patient, Dr. Fleischmann said. “It may be cheaper to the pharmacy benefit management firm, but this may not really help patient access to these medications. It is also not clear that nonmedical substitution will be effective in every patient nor has it been demonstrated that extrapolation is effective,” he wrote.
No disclosures were listed for the authors of the position statement. Dr. Fleischmann is a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Sanofi Aventis, and UCB.
SOURCES: Bridges S et al. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40388; and Fleischmann R. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40402
The American College of Rheumatology has shifted from a more cautious stance toward the use of biosimilars in clinical practice to now recommend in a new position statement that health care providers incorporate biosimilars, where appropriate, into treatment regimens for their patients living with rheumatic diseases.
“Now that biosimilars have been used successfully in Europe, with rigorously acquired data supporting their broader use, and , S. Louis Bridges Jr., MD, PhD, chair of the ACR Committee on Research, wrote with seven other authors of the position statement in Arthritis & Rheumatology.
The ACR position statement addresses the issues of immunogenicity, extrapolation of indications, interchangeability, substitution, switching, and cost surrounding biosimilars.
The position statement’s authors said they expect switching and nonmedical substitution to become as common in the United States as it is in the rest of the world. They do not anticipate efficacy and safety issues for biosimilars based on available data regarding switching between reference products and biosimilars and their understanding of product drift.
“However, we encourage vigorous postmarketing surveillance of both biosimilars and their reference products as we enter the era where patients may undergo multiple switches as a result of insurance company and [pharmacy benefits manager] formulary preferences,” they said.
Immunogenicity
Concerns about immunogenicity for biosimilars approved in the United States have mostly been well addressed through studies showing similar frequencies of binding and neutralizing antidrug antibodies (ADA) in biosimilars and their reference products. Furthermore, no safety signals between biosimilars and their reference products have been observed that suggest a differential effect of ADA on efficacy, safety, or patient outcomes, the authors said. But they noted that “if immunogenicity findings are to be extrapolated from one disease to additional indications, the subjects being studied should be those most likely to develop ADA, such as subjects not receiving concomitant immunosuppressive medications.” The results of comparative immunogenicity studies carried out to date also indicate that “a patient who develops ADA to a reference drug with resultant loss of clinical response should not be switched to its biosimilar.”
Again, the authors said postmarketing pharmacovigilance using observational registry data would be critical to assessing the effect of switching on immunogenicity.
Extrapolation of indications
The extrapolation of biosimilars to reference product indications for which the biosimilar was not assessed in clinical trials continues to “be an area of uneasiness” among clinicians “who are surprised to find” that a biosimilar can be approved for inflammatory bowel disease in the absence of clinical trials in the relevant patient populations, the authors said. In geographic areas where it is not mandatory to use biosimilars, this lack of confidence in extrapolation of indications may limit their acceptance, the authors wrote, but data from studies such as NOR-SWITCH and DANBIO have provided reassuring evidence to support regulated extrapolation of indication for biosimilars.
However, since extrapolation of indications also applies to pediatric patients who often metabolize drugs faster than adults, the position paper says that “it may be important” to conduct pharmacodynamic and pharmacokinetic studies in children as well as postmarketing surveillance “since potential immunogenicity may be of particular importance in these younger patients with chronic diseases who might encounter several biological agents during their lifetime.”
Substitution, interchangeability, and switching
The “interchangeability” regulatory pathway in the United States that would allow substitution at the point of dispensing has not been finalized, but most states have enacted, or are in the process of enacting, legislation to regulate the practice, the statement says.
While substitution describes a change made by someone other than the prescriber, the authors note that switching defines the “intentional change initiated by a health care provider in partnership with the patient” for economic or medical reasons. Switching has been studied most often in open-label extension studies of biosimilar clinic trials and has shown no loss of efficacy or increase in adverse events.
Dr. Fleischmann contended that substitution, extrapolation, and interchangeability of biosimilars in clinical practice remain gray areas. For example, in a clinical trial, patients switching from a reference product to a biosimilar may show equivalency of clinical response and adverse events. “But as rheumatologists, we don’t treat groups of patients; we treat individual patients and here the results may be different,” he wrote in Arthritis & Rheumatology.
While the white paper appropriately points out that interchangeability among multiple biosimilars is a question that should be answered in postmarketing registries, Dr. Fleischmann noted that no interchangeability study has been reported, even though the FDA has issued guidance on how a study should be done.
“Although interchangeability may be safe and effective in many patients, until the results of such a study are available and properly analyzed, it is only conjecture that interchangeability is appropriate and safe,” he said.
Costs
The white paper acknowledged that the “only anticipated advantage” of a biosimilar over its reference product was lower cost, since both drugs should be therapeutically equivalent. “The degree to which the availability of biosimilars in the U.S. will drive down the cost of biologic therapy, and who will benefit from any cost reductions remains to be seen,” the authors wrote.
“To incentivize the use of biosimilars,” the authors suggested that “commercial and government insurance programs could harmonize drug prices with patients’ out-of-pocket costs and provider reimbursement. Currently, however, patients with commercial insurance are likely to have similar copayments for both biosimilars and originator biologics because of [pharmacy benefits manager]– or plan-mandated patient cost sharing. Also, patients’ out-of-pocket costs for biosimilars in the Medicare Part D (self-administered drug) program likely will be higher than for originator biologics because of a flaw that maintains, rather than reduces, biosimilar patient cost sharing in the coverage gap (also known as the “donut hole”) until 2020.”
It is not at all clear that a biosimilar would be cheaper for the individual patient, Dr. Fleischmann said. “It may be cheaper to the pharmacy benefit management firm, but this may not really help patient access to these medications. It is also not clear that nonmedical substitution will be effective in every patient nor has it been demonstrated that extrapolation is effective,” he wrote.
No disclosures were listed for the authors of the position statement. Dr. Fleischmann is a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Sanofi Aventis, and UCB.
SOURCES: Bridges S et al. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40388; and Fleischmann R. Arthritis Rheumatol. 2018 Feb 7. doi: 10.1002/art.40402
FROM ARTHRITIS & RHEUMATOLOGY
FDA approves infliximab biosimilar Ixifi for all of Remicade’s indications
The Food and Drug Administration has approved Ixifi (infliximab-qbtx), a biosimilar of Remicade, the original infliximab product. Ixifi is the third infliximab biosimilar to be approved by the FDA, and it is approved for all the same indications as Remicade, according to an announcement from its manufacturer, Pfizer.
Ixifi and Remicade are approved for the treatment of rheumatoid arthritis in combination with methotrexate, Crohn’s disease, pediatric Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.
The most common adverse events associated with Ixifi are upper respiratory infections, sinusitis, pharyngitis, infusion-related reactions, headache, and abdominal pain.
The Food and Drug Administration has approved Ixifi (infliximab-qbtx), a biosimilar of Remicade, the original infliximab product. Ixifi is the third infliximab biosimilar to be approved by the FDA, and it is approved for all the same indications as Remicade, according to an announcement from its manufacturer, Pfizer.
Ixifi and Remicade are approved for the treatment of rheumatoid arthritis in combination with methotrexate, Crohn’s disease, pediatric Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.
The most common adverse events associated with Ixifi are upper respiratory infections, sinusitis, pharyngitis, infusion-related reactions, headache, and abdominal pain.
The Food and Drug Administration has approved Ixifi (infliximab-qbtx), a biosimilar of Remicade, the original infliximab product. Ixifi is the third infliximab biosimilar to be approved by the FDA, and it is approved for all the same indications as Remicade, according to an announcement from its manufacturer, Pfizer.
Ixifi and Remicade are approved for the treatment of rheumatoid arthritis in combination with methotrexate, Crohn’s disease, pediatric Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.
The most common adverse events associated with Ixifi are upper respiratory infections, sinusitis, pharyngitis, infusion-related reactions, headache, and abdominal pain.
Testing for latent tuberculosis infection
While cases of active tuberculosis are relatively rare in the United States, TB is a major cause of morbidity and mortality worldwide. In the United States, there are an estimated 11 million individuals who have latent TB infection (LTBI). Without prophylactic treatment, somewhere between 4%-6% of individuals with LTBI will develop active disease during their lifetimes; roughly half of these cases will occur within a few years of the initial infection. Treatment of LTBI reduces – but does not eliminate – the risk for active disease, decreasing the consequences of active disease for the patient and the risk of transmitting infection to others.
Diagnostic tests for LTBI
The tuberculin skin test (TST) has been the standard method of diagnosing LTBI. It involves measuring induration caused by a delayed-type hypersensitivity reaction to Mycobacterium tuberculosis (Mtb) 2 or 3 days after injecting the reagent into the skin. The TST can result in false positives when detecting antibodies to BCG and nontuberculous mycobacteria, and false negatives when the patient does not demonstrate a robust immune response. A newer testing method is the Interferon Gamma Release Assay (IGRA), which involves phlebotomy, followed by a series of laboratory procedures that measure IFN-gamma release by T cells that have been sensitized to Mtb. The sensitivity of IGRA is similar to the TST, but it has better specificity; it is much less likely to react to antigens from BCG or nontuberculous mycobacteria. As detailed below, this guideline suggests a significantly more prominent role for IGRA, compared with previous recommendations.
Recommendation 1. Perform an IGRA, rather than a TST, in individuals 5 years or older who meet the following criteria: 1) are likely to be infected with Mtb; 2) have a low or intermediate risk of disease progression; 3) in whom it has been decided that testing for LTBI is warranted. A TST is an acceptable alternative, particularly if an IGRA is not available, is too costly, or is too burdensome. If an individual either has a history of BCG vaccination or is unlikely to return to have their TST read, then it is strongly recommended to use the IGRA as the test of choice.
Recommendation 2. There are insufficient data to recommend a preference for either a TST or an IGRA as the first-line diagnostic test in individuals 5 years or older who are likely to be infected with Mtb, who have a high risk of progression to active disease, and in whom it has been determined that diagnostic testing for LTBI infection is warranted; either test would be acceptable. In very high-risk patients, consider dual testing, with a positive result from either test (TST or IGRA) being considered positive.
Recommendation 3. Guidelines do not recommend testing for persons at low risk for Mtb infection. However, the authors recognize that testing in such persons may nevertheless be mandated in certain situations (for example in some school or child care settings). In these cases, the authors recommend performing an IGRA instead of a TST, to minimize the chance of a false-positive result, although a TST is an acceptable alternative. Furthermore, if the initial test is positive, they suggest performing a confirmatory test (either an IGRA or TST) and considering the person infected only if both tests are positive.
Recommendation 4. The authors suggest performing a TST rather than an IGRA in healthy children less than 5 years of age for whom it has been decided that diagnostic testing for LTBI is warranted. This recommendation reflects the limited body of evidence regarding IGRA testing in young children and the apparent decreased sensitivity (i.e. more false negatives) in this population, compared with TST use.
In the area of serial testing for TB infection, often done in health care and institutional settings, the guideline points out areas of uncertainty with IGRA testing. Specifically, the IGRA test is subject to variability in readings and boosting with antigen exposure that can complicate interpretation of apparent conversion on repeat testing. One longitudinal study showed conversion rates with IGRA to be six to nine times higher than that seen for the TST, and those conversions were thought to represent false positive tests. The guideline concludes that, “There is insufficient information available to guide the establishment of definitive criteria for the conversion.” The committee thought that a positive test in a low-risk individual was likely to be a false-positive result and recommended repeat testing. Because of the possibility of boosting with antigen exposure in situations where dual testing is anticipated, it may be preferable to obtain a specimen for IGRA prior to, or concurrently with TST placement.
Bottom line
Current guidelines suggest a more prominent role for IGRA in testing for LTBI, particularly when the likelihood of exposure is low and in situations where a person may have received BCG vaccination, or would be unlikely to return for TST reading.
Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Clark is associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.
Reference
Lewisohn DM et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Inf Dis. 2017;64(2):111-5.
While cases of active tuberculosis are relatively rare in the United States, TB is a major cause of morbidity and mortality worldwide. In the United States, there are an estimated 11 million individuals who have latent TB infection (LTBI). Without prophylactic treatment, somewhere between 4%-6% of individuals with LTBI will develop active disease during their lifetimes; roughly half of these cases will occur within a few years of the initial infection. Treatment of LTBI reduces – but does not eliminate – the risk for active disease, decreasing the consequences of active disease for the patient and the risk of transmitting infection to others.
Diagnostic tests for LTBI
The tuberculin skin test (TST) has been the standard method of diagnosing LTBI. It involves measuring induration caused by a delayed-type hypersensitivity reaction to Mycobacterium tuberculosis (Mtb) 2 or 3 days after injecting the reagent into the skin. The TST can result in false positives when detecting antibodies to BCG and nontuberculous mycobacteria, and false negatives when the patient does not demonstrate a robust immune response. A newer testing method is the Interferon Gamma Release Assay (IGRA), which involves phlebotomy, followed by a series of laboratory procedures that measure IFN-gamma release by T cells that have been sensitized to Mtb. The sensitivity of IGRA is similar to the TST, but it has better specificity; it is much less likely to react to antigens from BCG or nontuberculous mycobacteria. As detailed below, this guideline suggests a significantly more prominent role for IGRA, compared with previous recommendations.
Recommendation 1. Perform an IGRA, rather than a TST, in individuals 5 years or older who meet the following criteria: 1) are likely to be infected with Mtb; 2) have a low or intermediate risk of disease progression; 3) in whom it has been decided that testing for LTBI is warranted. A TST is an acceptable alternative, particularly if an IGRA is not available, is too costly, or is too burdensome. If an individual either has a history of BCG vaccination or is unlikely to return to have their TST read, then it is strongly recommended to use the IGRA as the test of choice.
Recommendation 2. There are insufficient data to recommend a preference for either a TST or an IGRA as the first-line diagnostic test in individuals 5 years or older who are likely to be infected with Mtb, who have a high risk of progression to active disease, and in whom it has been determined that diagnostic testing for LTBI infection is warranted; either test would be acceptable. In very high-risk patients, consider dual testing, with a positive result from either test (TST or IGRA) being considered positive.
Recommendation 3. Guidelines do not recommend testing for persons at low risk for Mtb infection. However, the authors recognize that testing in such persons may nevertheless be mandated in certain situations (for example in some school or child care settings). In these cases, the authors recommend performing an IGRA instead of a TST, to minimize the chance of a false-positive result, although a TST is an acceptable alternative. Furthermore, if the initial test is positive, they suggest performing a confirmatory test (either an IGRA or TST) and considering the person infected only if both tests are positive.
Recommendation 4. The authors suggest performing a TST rather than an IGRA in healthy children less than 5 years of age for whom it has been decided that diagnostic testing for LTBI is warranted. This recommendation reflects the limited body of evidence regarding IGRA testing in young children and the apparent decreased sensitivity (i.e. more false negatives) in this population, compared with TST use.
In the area of serial testing for TB infection, often done in health care and institutional settings, the guideline points out areas of uncertainty with IGRA testing. Specifically, the IGRA test is subject to variability in readings and boosting with antigen exposure that can complicate interpretation of apparent conversion on repeat testing. One longitudinal study showed conversion rates with IGRA to be six to nine times higher than that seen for the TST, and those conversions were thought to represent false positive tests. The guideline concludes that, “There is insufficient information available to guide the establishment of definitive criteria for the conversion.” The committee thought that a positive test in a low-risk individual was likely to be a false-positive result and recommended repeat testing. Because of the possibility of boosting with antigen exposure in situations where dual testing is anticipated, it may be preferable to obtain a specimen for IGRA prior to, or concurrently with TST placement.
Bottom line
Current guidelines suggest a more prominent role for IGRA in testing for LTBI, particularly when the likelihood of exposure is low and in situations where a person may have received BCG vaccination, or would be unlikely to return for TST reading.
Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Clark is associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.
Reference
Lewisohn DM et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Inf Dis. 2017;64(2):111-5.
While cases of active tuberculosis are relatively rare in the United States, TB is a major cause of morbidity and mortality worldwide. In the United States, there are an estimated 11 million individuals who have latent TB infection (LTBI). Without prophylactic treatment, somewhere between 4%-6% of individuals with LTBI will develop active disease during their lifetimes; roughly half of these cases will occur within a few years of the initial infection. Treatment of LTBI reduces – but does not eliminate – the risk for active disease, decreasing the consequences of active disease for the patient and the risk of transmitting infection to others.
Diagnostic tests for LTBI
The tuberculin skin test (TST) has been the standard method of diagnosing LTBI. It involves measuring induration caused by a delayed-type hypersensitivity reaction to Mycobacterium tuberculosis (Mtb) 2 or 3 days after injecting the reagent into the skin. The TST can result in false positives when detecting antibodies to BCG and nontuberculous mycobacteria, and false negatives when the patient does not demonstrate a robust immune response. A newer testing method is the Interferon Gamma Release Assay (IGRA), which involves phlebotomy, followed by a series of laboratory procedures that measure IFN-gamma release by T cells that have been sensitized to Mtb. The sensitivity of IGRA is similar to the TST, but it has better specificity; it is much less likely to react to antigens from BCG or nontuberculous mycobacteria. As detailed below, this guideline suggests a significantly more prominent role for IGRA, compared with previous recommendations.
Recommendation 1. Perform an IGRA, rather than a TST, in individuals 5 years or older who meet the following criteria: 1) are likely to be infected with Mtb; 2) have a low or intermediate risk of disease progression; 3) in whom it has been decided that testing for LTBI is warranted. A TST is an acceptable alternative, particularly if an IGRA is not available, is too costly, or is too burdensome. If an individual either has a history of BCG vaccination or is unlikely to return to have their TST read, then it is strongly recommended to use the IGRA as the test of choice.
Recommendation 2. There are insufficient data to recommend a preference for either a TST or an IGRA as the first-line diagnostic test in individuals 5 years or older who are likely to be infected with Mtb, who have a high risk of progression to active disease, and in whom it has been determined that diagnostic testing for LTBI infection is warranted; either test would be acceptable. In very high-risk patients, consider dual testing, with a positive result from either test (TST or IGRA) being considered positive.
Recommendation 3. Guidelines do not recommend testing for persons at low risk for Mtb infection. However, the authors recognize that testing in such persons may nevertheless be mandated in certain situations (for example in some school or child care settings). In these cases, the authors recommend performing an IGRA instead of a TST, to minimize the chance of a false-positive result, although a TST is an acceptable alternative. Furthermore, if the initial test is positive, they suggest performing a confirmatory test (either an IGRA or TST) and considering the person infected only if both tests are positive.
Recommendation 4. The authors suggest performing a TST rather than an IGRA in healthy children less than 5 years of age for whom it has been decided that diagnostic testing for LTBI is warranted. This recommendation reflects the limited body of evidence regarding IGRA testing in young children and the apparent decreased sensitivity (i.e. more false negatives) in this population, compared with TST use.
In the area of serial testing for TB infection, often done in health care and institutional settings, the guideline points out areas of uncertainty with IGRA testing. Specifically, the IGRA test is subject to variability in readings and boosting with antigen exposure that can complicate interpretation of apparent conversion on repeat testing. One longitudinal study showed conversion rates with IGRA to be six to nine times higher than that seen for the TST, and those conversions were thought to represent false positive tests. The guideline concludes that, “There is insufficient information available to guide the establishment of definitive criteria for the conversion.” The committee thought that a positive test in a low-risk individual was likely to be a false-positive result and recommended repeat testing. Because of the possibility of boosting with antigen exposure in situations where dual testing is anticipated, it may be preferable to obtain a specimen for IGRA prior to, or concurrently with TST placement.
Bottom line
Current guidelines suggest a more prominent role for IGRA in testing for LTBI, particularly when the likelihood of exposure is low and in situations where a person may have received BCG vaccination, or would be unlikely to return for TST reading.
Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Clark is associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.
Reference
Lewisohn DM et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Inf Dis. 2017;64(2):111-5.
TNFi response evaluations may conflict when fibromyalgia, axial SpA coexist
The concomitant presence of both axial spondyloarthritis (axSpA) and fibromyalgia affects response to tumor necrosis factor (TNF) blockers through increased symptom severity on patient-reported outcomes but not on more objective measurements, according to findings from a prospective, longitudinal study.
Although reports have less frequently examined the relationship between fibromyalgia diagnosis and disease activity in patients who have rheumatologist-diagnosed axSpA than they have in patients with rheumatoid arthritis, those reports have indicated that patients with axSpA and concomitant fibromyalgia tend to present with higher disease activity on measures such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the investigators wrote in Annals of the Rheumatic Diseases.
In this prospective, longitudinal study, a total of 508 adult patients with axSpA from 65 centers first attended a baseline visit, then 12 weeks after commencing treatment with TNF blockers, they attended an “effectiveness visit” in which they were evaluated for a response on the BASDAI. This response was defined as a reduction of at least 50% or two units, compared with baseline measurements. Furthermore, a total of 37.8% tested positive at baseline on the self-reported Fibromyalgia Rapid Screening Tool (FiRST) questionnaire, defined as a score of 5 or 6 out of 6.
These patients testing positive on FiRST at baseline were more likely to be female (55.7% vs. 41.1%), to have a history of peripheral enthesitis (64.7% vs. 47.8%), and to have a higher disease severity at baseline on the BASDAI and Ankylosing Spondylitis Disease Activity Score at baseline (6.5 vs. 5.1 and 3.5 vs. 3.2, respectively). They were also were more likely to be taking antidepressants (26.8% vs. 16.2%).
Patients who had fibromyalgia according to FiRST presented less frequently with a BASDAI response (87 of 192; 45.3%) after 12 weeks, compared with patients who had only axSpA at baseline (171 of 316; 54.1%). But this difference did not reach statistical significance in both univariate or multivariate analyses. However, nearly all of the secondary endpoints of response, such as various levels of response on the Assessment of SpondyloArthritis international Society criteria and the Ankylosing Spondylitis Disease Activity Score, were achieved significantly less often among patients who also had fibromyalgia.
Although BASDAI response was not different between the groups, the investigators said that fibromyalgia had a negative effect on TNF blocker response that “seems related to the instruments used in its evaluation rather than a different treatment effect of the molecule.”
Sensitivity analyses that used the 1990 American College of Rheumatology criteria to define the presence of fibromyalgia rather than the FiRST questionnaire result at baseline did not find any differences in TNF blocker responses between the groups on the main endpoint and most of the secondary endpoints. The ACR criteria classified fibromyalgia in 16.1% of the patients.
Another set of sensitivity analyses that used only the FiRST results at 12 weeks to diagnose fibromyalgia found that fibromyalgia patients had lower responses to treatment on nearly all endpoints. Only 18.7% of patients tested positive on the FiRST questionnaire at 12 weeks.
The change in C-reactive protein (CRP) levels at 12 weeks was not different between the groups of patients regardless of the definition used for fibromyalgia.
The researchers observed a decreased frequency of HLA-B27 positivity, radiographic sacroiliitis, and MRI sacroiliitis in people with both diseases. The authors called this finding “intriguing” and said it “might suggest that some patients participating in the trial might have been misdiagnosed and were in fact suffering from [fibromyalgia] only.”
But other clinical features suggestive of axSpA, such as uveitis, psoriasis, and inflammatory bowel disease, were equally present across the different groups.
Overall, “these results suggest that there is indeed an impact on the treatment response, but seems more related to the patient-reported outcomes used in the effectiveness endpoints, as suggested by the absence of difference across groups for the objective biological parameters (i.e., CRP).”
Dr. Moltó and her colleagues said their findings highlighted the importance not only of evaluating the presence of coexisting fibromyalgia in patients with axSpA when evaluating treatment response but also in determining treatment targets.
“This seems particularly important for decision of the treatment target in patients with axSpA when applying a treat-to-target strategy: For example, remission might not be a feasible target for these patients [with concomitant fibromyalgia] who will not likely reach this state, but should rather aim for a significant change or focus in only on objective parameters (i.e., CRP),” they concluded.
The study was funded by an unrestricted grant from Merck Sharp & Dohme. The authors declared having no competing interests.
SOURCE: Moltó A et al. Ann Rheum Dis. 2017 Nov 28. doi: 10.1136/annrheumdis-2017-212378.
The concomitant presence of both axial spondyloarthritis (axSpA) and fibromyalgia affects response to tumor necrosis factor (TNF) blockers through increased symptom severity on patient-reported outcomes but not on more objective measurements, according to findings from a prospective, longitudinal study.
Although reports have less frequently examined the relationship between fibromyalgia diagnosis and disease activity in patients who have rheumatologist-diagnosed axSpA than they have in patients with rheumatoid arthritis, those reports have indicated that patients with axSpA and concomitant fibromyalgia tend to present with higher disease activity on measures such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the investigators wrote in Annals of the Rheumatic Diseases.
In this prospective, longitudinal study, a total of 508 adult patients with axSpA from 65 centers first attended a baseline visit, then 12 weeks after commencing treatment with TNF blockers, they attended an “effectiveness visit” in which they were evaluated for a response on the BASDAI. This response was defined as a reduction of at least 50% or two units, compared with baseline measurements. Furthermore, a total of 37.8% tested positive at baseline on the self-reported Fibromyalgia Rapid Screening Tool (FiRST) questionnaire, defined as a score of 5 or 6 out of 6.
These patients testing positive on FiRST at baseline were more likely to be female (55.7% vs. 41.1%), to have a history of peripheral enthesitis (64.7% vs. 47.8%), and to have a higher disease severity at baseline on the BASDAI and Ankylosing Spondylitis Disease Activity Score at baseline (6.5 vs. 5.1 and 3.5 vs. 3.2, respectively). They were also were more likely to be taking antidepressants (26.8% vs. 16.2%).
Patients who had fibromyalgia according to FiRST presented less frequently with a BASDAI response (87 of 192; 45.3%) after 12 weeks, compared with patients who had only axSpA at baseline (171 of 316; 54.1%). But this difference did not reach statistical significance in both univariate or multivariate analyses. However, nearly all of the secondary endpoints of response, such as various levels of response on the Assessment of SpondyloArthritis international Society criteria and the Ankylosing Spondylitis Disease Activity Score, were achieved significantly less often among patients who also had fibromyalgia.
Although BASDAI response was not different between the groups, the investigators said that fibromyalgia had a negative effect on TNF blocker response that “seems related to the instruments used in its evaluation rather than a different treatment effect of the molecule.”
Sensitivity analyses that used the 1990 American College of Rheumatology criteria to define the presence of fibromyalgia rather than the FiRST questionnaire result at baseline did not find any differences in TNF blocker responses between the groups on the main endpoint and most of the secondary endpoints. The ACR criteria classified fibromyalgia in 16.1% of the patients.
Another set of sensitivity analyses that used only the FiRST results at 12 weeks to diagnose fibromyalgia found that fibromyalgia patients had lower responses to treatment on nearly all endpoints. Only 18.7% of patients tested positive on the FiRST questionnaire at 12 weeks.
The change in C-reactive protein (CRP) levels at 12 weeks was not different between the groups of patients regardless of the definition used for fibromyalgia.
The researchers observed a decreased frequency of HLA-B27 positivity, radiographic sacroiliitis, and MRI sacroiliitis in people with both diseases. The authors called this finding “intriguing” and said it “might suggest that some patients participating in the trial might have been misdiagnosed and were in fact suffering from [fibromyalgia] only.”
But other clinical features suggestive of axSpA, such as uveitis, psoriasis, and inflammatory bowel disease, were equally present across the different groups.
Overall, “these results suggest that there is indeed an impact on the treatment response, but seems more related to the patient-reported outcomes used in the effectiveness endpoints, as suggested by the absence of difference across groups for the objective biological parameters (i.e., CRP).”
Dr. Moltó and her colleagues said their findings highlighted the importance not only of evaluating the presence of coexisting fibromyalgia in patients with axSpA when evaluating treatment response but also in determining treatment targets.
“This seems particularly important for decision of the treatment target in patients with axSpA when applying a treat-to-target strategy: For example, remission might not be a feasible target for these patients [with concomitant fibromyalgia] who will not likely reach this state, but should rather aim for a significant change or focus in only on objective parameters (i.e., CRP),” they concluded.
The study was funded by an unrestricted grant from Merck Sharp & Dohme. The authors declared having no competing interests.
SOURCE: Moltó A et al. Ann Rheum Dis. 2017 Nov 28. doi: 10.1136/annrheumdis-2017-212378.
The concomitant presence of both axial spondyloarthritis (axSpA) and fibromyalgia affects response to tumor necrosis factor (TNF) blockers through increased symptom severity on patient-reported outcomes but not on more objective measurements, according to findings from a prospective, longitudinal study.
Although reports have less frequently examined the relationship between fibromyalgia diagnosis and disease activity in patients who have rheumatologist-diagnosed axSpA than they have in patients with rheumatoid arthritis, those reports have indicated that patients with axSpA and concomitant fibromyalgia tend to present with higher disease activity on measures such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the investigators wrote in Annals of the Rheumatic Diseases.
In this prospective, longitudinal study, a total of 508 adult patients with axSpA from 65 centers first attended a baseline visit, then 12 weeks after commencing treatment with TNF blockers, they attended an “effectiveness visit” in which they were evaluated for a response on the BASDAI. This response was defined as a reduction of at least 50% or two units, compared with baseline measurements. Furthermore, a total of 37.8% tested positive at baseline on the self-reported Fibromyalgia Rapid Screening Tool (FiRST) questionnaire, defined as a score of 5 or 6 out of 6.
These patients testing positive on FiRST at baseline were more likely to be female (55.7% vs. 41.1%), to have a history of peripheral enthesitis (64.7% vs. 47.8%), and to have a higher disease severity at baseline on the BASDAI and Ankylosing Spondylitis Disease Activity Score at baseline (6.5 vs. 5.1 and 3.5 vs. 3.2, respectively). They were also were more likely to be taking antidepressants (26.8% vs. 16.2%).
Patients who had fibromyalgia according to FiRST presented less frequently with a BASDAI response (87 of 192; 45.3%) after 12 weeks, compared with patients who had only axSpA at baseline (171 of 316; 54.1%). But this difference did not reach statistical significance in both univariate or multivariate analyses. However, nearly all of the secondary endpoints of response, such as various levels of response on the Assessment of SpondyloArthritis international Society criteria and the Ankylosing Spondylitis Disease Activity Score, were achieved significantly less often among patients who also had fibromyalgia.
Although BASDAI response was not different between the groups, the investigators said that fibromyalgia had a negative effect on TNF blocker response that “seems related to the instruments used in its evaluation rather than a different treatment effect of the molecule.”
Sensitivity analyses that used the 1990 American College of Rheumatology criteria to define the presence of fibromyalgia rather than the FiRST questionnaire result at baseline did not find any differences in TNF blocker responses between the groups on the main endpoint and most of the secondary endpoints. The ACR criteria classified fibromyalgia in 16.1% of the patients.
Another set of sensitivity analyses that used only the FiRST results at 12 weeks to diagnose fibromyalgia found that fibromyalgia patients had lower responses to treatment on nearly all endpoints. Only 18.7% of patients tested positive on the FiRST questionnaire at 12 weeks.
The change in C-reactive protein (CRP) levels at 12 weeks was not different between the groups of patients regardless of the definition used for fibromyalgia.
The researchers observed a decreased frequency of HLA-B27 positivity, radiographic sacroiliitis, and MRI sacroiliitis in people with both diseases. The authors called this finding “intriguing” and said it “might suggest that some patients participating in the trial might have been misdiagnosed and were in fact suffering from [fibromyalgia] only.”
But other clinical features suggestive of axSpA, such as uveitis, psoriasis, and inflammatory bowel disease, were equally present across the different groups.
Overall, “these results suggest that there is indeed an impact on the treatment response, but seems more related to the patient-reported outcomes used in the effectiveness endpoints, as suggested by the absence of difference across groups for the objective biological parameters (i.e., CRP).”
Dr. Moltó and her colleagues said their findings highlighted the importance not only of evaluating the presence of coexisting fibromyalgia in patients with axSpA when evaluating treatment response but also in determining treatment targets.
“This seems particularly important for decision of the treatment target in patients with axSpA when applying a treat-to-target strategy: For example, remission might not be a feasible target for these patients [with concomitant fibromyalgia] who will not likely reach this state, but should rather aim for a significant change or focus in only on objective parameters (i.e., CRP),” they concluded.
The study was funded by an unrestricted grant from Merck Sharp & Dohme. The authors declared having no competing interests.
SOURCE: Moltó A et al. Ann Rheum Dis. 2017 Nov 28. doi: 10.1136/annrheumdis-2017-212378.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: Patients with both axSpA and fibromyalgia presented less frequently with a BASDAI response after 12 weeks than did patients without both diseases (45.3% vs. 54.1%), but the finding did not reach statistical significance.
Data source: Prospective, longitudinal study of 508 adult patients with rheumatologist-diagnosed axSpA.
Disclosures: The study was funded by an unrestricted grant from Merck Sharp & Dohme. The authors declared having no competing interests.
Source: Moltó A et al. Ann Rheum Dis. 2017 Nov 28. doi: 10.1136/annrheumdis-2017-212378.
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.
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
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.
