Adalimumab effective in nonpsoriatic peripheral spondyloarthritis

Adalimumab alleviated symptoms and improved physical functions in certain patients with active nonpsoriatic peripheral spondyloarthritis in the first 12 weeks of treatment in the ongoing ABILITY-2 trial.

The findings of the trial, which investigators called the “first global, multicenter, randomized, controlled trial” in patients with nonpsoriatic peripheral spondyloarthritis (SpA), add to the growing list of evidence that tumor necrosis factor inhibitors are effective in treating spondyloarthritis (Arthritis Rheumatol. 2014 Dec. 29 [doi:10.1002/art.39008]).

The randomized, double-blind study examined 165 patients aged at least 18 years with active, nonpsoriatic peripheral SpA. The patients met Assessment of Spondyloarthritis International Society (ASAS) peripheral SpA criteria rather than the “older” European Spondyloarthropathy Study Group (ESSG) criteria and had inadequate response to at least two nonsteroidal anti-inflammatory drugs (NSAIDs) or were intolerant to or had a contraindication for NSAIDs. These subjects were placed into cohorts receiving either 40 mg of adalimumab or a placebo for 12 weeks followed by a 144-week-long open-label period. After randomization, 84 subjects were placed on the adalimumab regimen and the remaining 81 were given a placebo. All patients will enter an open-label, 144-week treatment period on adalimumab, according to lead author Dr. Philip Mease of the University of Washington, Seattle, and his coauthors.

The investigators reported that the groups had similar baseline demographics, including 52%-57% being female and mean ages of 38.5-42.5 years, and disease characteristics, including mean symptom duration of 6.6-7.7 years and time since diagnosis of 3.0-4.2 years.

The investigators used a novel primary outcome measurement that required at least 40% improvement in Patient Global Assessments of Disease Activity (PGA) and Pain (PGA-pain) scores from baseline (with at least 20 mm absolute improvement on a visual analog scale) and at least 40% improvement in one or more of the following areas: swollen joint (SJC) and tender joint counts (TJC); enthesitis count; or dactylitis count. Subjects who achieved the primary endpoint of peripheral SpA response criteria were noted as PSpARC 40; individuals who reached other levels of improvement – 20%, 50%, and 70%, with at least 10, 20, or 30 mm absolute improvement, respectively – were noted as PSpARC 20, PSpARC 50, and PSpARC 70, respectively.

After 12 weeks of treatment, nearly twice as many adalimumab-treated patients achieved PSpARC 40 as did placebo-treated patients (39% [33 of 84] vs. 20% [16 of 81]; P = .006). Also, the proportions of patients who achieved PSpARC 20, PSpARC 50, and PSpARC 70 were higher in subjects on adalimumab than in those receiving the placebo: 56% vs. 37% (P < .05), 34% vs. 11% (P < .001), and 22% vs. 3% (P < .001), respectively.

Significant differences between the two treatments were noted by investigators as early as week 2 of the trial. In subjects who achieved PSpARC 40, investigators recorded a minimum 40% improvement and at least 20-mm improvement in the PGA (54% adalimumab vs. 29% placebo; P < .001) and PGA-pain (54% adalimumab vs. 31% placebo; P = .004), and at least 40% improvement in TJC/SJC (57% adalimumab vs. 30% placebo; P < .001). Adverse effects between both cohorts were not significantly different.

“The safety profile of adalimumab in this patient population was consistent with the well-established safety of adalimumab in multiple immune-mediated diseases, [but] longer-term data are needed to confirm and support the favorable benefit-risk profile of adalimumab in nonpsoriatic peripheral SpA observed in this study,” Dr. Mease and his associates concluded.

In an interview, Dr. Grant Louie of Johns Hopkins Arthritis Center in Baltimore, who was not involved in the study, noted that the results are significant because the investigators used such a “rigorously controlled environment” and a more relevant classification system for diagnosing patients.

“When using the ASAS criteria for classifying peripheral spondyloarthritis, it introduces a little more heterogeneity into the patient population,” said Dr. Louie. “This new system incorporates what used to be referred to as undifferentiated spondyloarthritis as well as patients who have reactive arthritis [and] some with inflammatory bowel disease-associated arthritis, while excluding patients who have psoriatic arthritis and ankylosing spondylitis. So a big advantage is that you can incorporate some of these patients earlier in the process so they can undergo the appropriate treatments.”

However, Dr. Louie explained that he had reservations with how the study measured its primary outcome and how clinicians and researchers will be able to use these data without having an externally validated endpoint.

“The biggest caveat – which the authors themselves do mention in the paper, to their credit – is that they’re introducing a new primary study endpoint,” Dr. Louie said. “This composite score that they’re using, which takes into account factors like tender and swollen joints, has not been validated in any external study. Without knowing if the primary endpoint has validity and reliability, I am a little skeptical.”

Dr. Dafna A. Gladman of the University of Toronto shared some of Dr. Louie’s skepticism of the primary endpoint, but credits the investigators with creating a measure that appears to have “construct validity, as well as sensitivity to change.”

In Dr. Gladman’s editorial (Arthritis Rheumatol. 2014 Dec. 29 [doi:10.1002/art.39014]), she noted that “the development of the measure is not described. Was it developed through a Delphi process? Has it shown face and construct validity in peripheral SpA? Has it shown test retest reliability? What we do know is that this measure distinguished between drug and placebo treated patients, [that] the majority of the response was related to the patient reported outcome which was a prerequisite and to the joint count item, [and] that the individual measures tested in this study showed the same results. One could then conclude that the new measure has construct validity, as well as sensitivity to change and thus would be acceptable as the primary outcome measure in this study.”

The ABILITY-2 study was funded by AbbVie, which markets adalimumab. Two authors are employees of the company. All other authors reported receiving grant/research support, consulting fees, and/or speaking fees from AbbVie and other companies that market biologics.

[email protected]

Adalimumab alleviated symptoms and improved physical functions in certain patients with active nonpsoriatic peripheral spondyloarthritis in the first 12 weeks of treatment in the ongoing ABILITY-2 trial.

The findings of the trial, which investigators called the “first global, multicenter, randomized, controlled trial” in patients with nonpsoriatic peripheral spondyloarthritis (SpA), add to the growing list of evidence that tumor necrosis factor inhibitors are effective in treating spondyloarthritis (Arthritis Rheumatol. 2014 Dec. 29 [doi:10.1002/art.39008]).

The randomized, double-blind study examined 165 patients aged at least 18 years with active, nonpsoriatic peripheral SpA. The patients met Assessment of Spondyloarthritis International Society (ASAS) peripheral SpA criteria rather than the “older” European Spondyloarthropathy Study Group (ESSG) criteria and had inadequate response to at least two nonsteroidal anti-inflammatory drugs (NSAIDs) or were intolerant to or had a contraindication for NSAIDs. These subjects were placed into cohorts receiving either 40 mg of adalimumab or a placebo for 12 weeks followed by a 144-week-long open-label period. After randomization, 84 subjects were placed on the adalimumab regimen and the remaining 81 were given a placebo. All patients will enter an open-label, 144-week treatment period on adalimumab, according to lead author Dr. Philip Mease of the University of Washington, Seattle, and his coauthors.

The investigators reported that the groups had similar baseline demographics, including 52%-57% being female and mean ages of 38.5-42.5 years, and disease characteristics, including mean symptom duration of 6.6-7.7 years and time since diagnosis of 3.0-4.2 years.

The investigators used a novel primary outcome measurement that required at least 40% improvement in Patient Global Assessments of Disease Activity (PGA) and Pain (PGA-pain) scores from baseline (with at least 20 mm absolute improvement on a visual analog scale) and at least 40% improvement in one or more of the following areas: swollen joint (SJC) and tender joint counts (TJC); enthesitis count; or dactylitis count. Subjects who achieved the primary endpoint of peripheral SpA response criteria were noted as PSpARC 40; individuals who reached other levels of improvement – 20%, 50%, and 70%, with at least 10, 20, or 30 mm absolute improvement, respectively – were noted as PSpARC 20, PSpARC 50, and PSpARC 70, respectively.

After 12 weeks of treatment, nearly twice as many adalimumab-treated patients achieved PSpARC 40 as did placebo-treated patients (39% [33 of 84] vs. 20% [16 of 81]; P = .006). Also, the proportions of patients who achieved PSpARC 20, PSpARC 50, and PSpARC 70 were higher in subjects on adalimumab than in those receiving the placebo: 56% vs. 37% (P < .05), 34% vs. 11% (P < .001), and 22% vs. 3% (P < .001), respectively.

Significant differences between the two treatments were noted by investigators as early as week 2 of the trial. In subjects who achieved PSpARC 40, investigators recorded a minimum 40% improvement and at least 20-mm improvement in the PGA (54% adalimumab vs. 29% placebo; P < .001) and PGA-pain (54% adalimumab vs. 31% placebo; P = .004), and at least 40% improvement in TJC/SJC (57% adalimumab vs. 30% placebo; P < .001). Adverse effects between both cohorts were not significantly different.

“The safety profile of adalimumab in this patient population was consistent with the well-established safety of adalimumab in multiple immune-mediated diseases, [but] longer-term data are needed to confirm and support the favorable benefit-risk profile of adalimumab in nonpsoriatic peripheral SpA observed in this study,” Dr. Mease and his associates concluded.

In an interview, Dr. Grant Louie of Johns Hopkins Arthritis Center in Baltimore, who was not involved in the study, noted that the results are significant because the investigators used such a “rigorously controlled environment” and a more relevant classification system for diagnosing patients.

“When using the ASAS criteria for classifying peripheral spondyloarthritis, it introduces a little more heterogeneity into the patient population,” said Dr. Louie. “This new system incorporates what used to be referred to as undifferentiated spondyloarthritis as well as patients who have reactive arthritis [and] some with inflammatory bowel disease-associated arthritis, while excluding patients who have psoriatic arthritis and ankylosing spondylitis. So a big advantage is that you can incorporate some of these patients earlier in the process so they can undergo the appropriate treatments.”

However, Dr. Louie explained that he had reservations with how the study measured its primary outcome and how clinicians and researchers will be able to use these data without having an externally validated endpoint.

“The biggest caveat – which the authors themselves do mention in the paper, to their credit – is that they’re introducing a new primary study endpoint,” Dr. Louie said. “This composite score that they’re using, which takes into account factors like tender and swollen joints, has not been validated in any external study. Without knowing if the primary endpoint has validity and reliability, I am a little skeptical.”

Dr. Dafna A. Gladman of the University of Toronto shared some of Dr. Louie’s skepticism of the primary endpoint, but credits the investigators with creating a measure that appears to have “construct validity, as well as sensitivity to change.”

In Dr. Gladman’s editorial (Arthritis Rheumatol. 2014 Dec. 29 [doi:10.1002/art.39014]), she noted that “the development of the measure is not described. Was it developed through a Delphi process? Has it shown face and construct validity in peripheral SpA? Has it shown test retest reliability? What we do know is that this measure distinguished between drug and placebo treated patients, [that] the majority of the response was related to the patient reported outcome which was a prerequisite and to the joint count item, [and] that the individual measures tested in this study showed the same results. One could then conclude that the new measure has construct validity, as well as sensitivity to change and thus would be acceptable as the primary outcome measure in this study.”

The ABILITY-2 study was funded by AbbVie, which markets adalimumab. Two authors are employees of the company. All other authors reported receiving grant/research support, consulting fees, and/or speaking fees from AbbVie and other companies that market biologics.

[email protected]

Adalimumab alleviated symptoms and improved physical functions in certain patients with active nonpsoriatic peripheral spondyloarthritis in the first 12 weeks of treatment in the ongoing ABILITY-2 trial.

The findings of the trial, which investigators called the “first global, multicenter, randomized, controlled trial” in patients with nonpsoriatic peripheral spondyloarthritis (SpA), add to the growing list of evidence that tumor necrosis factor inhibitors are effective in treating spondyloarthritis (Arthritis Rheumatol. 2014 Dec. 29 [doi:10.1002/art.39008]).

The randomized, double-blind study examined 165 patients aged at least 18 years with active, nonpsoriatic peripheral SpA. The patients met Assessment of Spondyloarthritis International Society (ASAS) peripheral SpA criteria rather than the “older” European Spondyloarthropathy Study Group (ESSG) criteria and had inadequate response to at least two nonsteroidal anti-inflammatory drugs (NSAIDs) or were intolerant to or had a contraindication for NSAIDs. These subjects were placed into cohorts receiving either 40 mg of adalimumab or a placebo for 12 weeks followed by a 144-week-long open-label period. After randomization, 84 subjects were placed on the adalimumab regimen and the remaining 81 were given a placebo. All patients will enter an open-label, 144-week treatment period on adalimumab, according to lead author Dr. Philip Mease of the University of Washington, Seattle, and his coauthors.

The investigators reported that the groups had similar baseline demographics, including 52%-57% being female and mean ages of 38.5-42.5 years, and disease characteristics, including mean symptom duration of 6.6-7.7 years and time since diagnosis of 3.0-4.2 years.

The investigators used a novel primary outcome measurement that required at least 40% improvement in Patient Global Assessments of Disease Activity (PGA) and Pain (PGA-pain) scores from baseline (with at least 20 mm absolute improvement on a visual analog scale) and at least 40% improvement in one or more of the following areas: swollen joint (SJC) and tender joint counts (TJC); enthesitis count; or dactylitis count. Subjects who achieved the primary endpoint of peripheral SpA response criteria were noted as PSpARC 40; individuals who reached other levels of improvement – 20%, 50%, and 70%, with at least 10, 20, or 30 mm absolute improvement, respectively – were noted as PSpARC 20, PSpARC 50, and PSpARC 70, respectively.

After 12 weeks of treatment, nearly twice as many adalimumab-treated patients achieved PSpARC 40 as did placebo-treated patients (39% [33 of 84] vs. 20% [16 of 81]; P = .006). Also, the proportions of patients who achieved PSpARC 20, PSpARC 50, and PSpARC 70 were higher in subjects on adalimumab than in those receiving the placebo: 56% vs. 37% (P < .05), 34% vs. 11% (P < .001), and 22% vs. 3% (P < .001), respectively.

Significant differences between the two treatments were noted by investigators as early as week 2 of the trial. In subjects who achieved PSpARC 40, investigators recorded a minimum 40% improvement and at least 20-mm improvement in the PGA (54% adalimumab vs. 29% placebo; P < .001) and PGA-pain (54% adalimumab vs. 31% placebo; P = .004), and at least 40% improvement in TJC/SJC (57% adalimumab vs. 30% placebo; P < .001). Adverse effects between both cohorts were not significantly different.

“The safety profile of adalimumab in this patient population was consistent with the well-established safety of adalimumab in multiple immune-mediated diseases, [but] longer-term data are needed to confirm and support the favorable benefit-risk profile of adalimumab in nonpsoriatic peripheral SpA observed in this study,” Dr. Mease and his associates concluded.

In an interview, Dr. Grant Louie of Johns Hopkins Arthritis Center in Baltimore, who was not involved in the study, noted that the results are significant because the investigators used such a “rigorously controlled environment” and a more relevant classification system for diagnosing patients.

“When using the ASAS criteria for classifying peripheral spondyloarthritis, it introduces a little more heterogeneity into the patient population,” said Dr. Louie. “This new system incorporates what used to be referred to as undifferentiated spondyloarthritis as well as patients who have reactive arthritis [and] some with inflammatory bowel disease-associated arthritis, while excluding patients who have psoriatic arthritis and ankylosing spondylitis. So a big advantage is that you can incorporate some of these patients earlier in the process so they can undergo the appropriate treatments.”

However, Dr. Louie explained that he had reservations with how the study measured its primary outcome and how clinicians and researchers will be able to use these data without having an externally validated endpoint.

“The biggest caveat – which the authors themselves do mention in the paper, to their credit – is that they’re introducing a new primary study endpoint,” Dr. Louie said. “This composite score that they’re using, which takes into account factors like tender and swollen joints, has not been validated in any external study. Without knowing if the primary endpoint has validity and reliability, I am a little skeptical.”

Dr. Dafna A. Gladman of the University of Toronto shared some of Dr. Louie’s skepticism of the primary endpoint, but credits the investigators with creating a measure that appears to have “construct validity, as well as sensitivity to change.”

In Dr. Gladman’s editorial (Arthritis Rheumatol. 2014 Dec. 29 [doi:10.1002/art.39014]), she noted that “the development of the measure is not described. Was it developed through a Delphi process? Has it shown face and construct validity in peripheral SpA? Has it shown test retest reliability? What we do know is that this measure distinguished between drug and placebo treated patients, [that] the majority of the response was related to the patient reported outcome which was a prerequisite and to the joint count item, [and] that the individual measures tested in this study showed the same results. One could then conclude that the new measure has construct validity, as well as sensitivity to change and thus would be acceptable as the primary outcome measure in this study.”

The ABILITY-2 study was funded by AbbVie, which markets adalimumab. Two authors are employees of the company. All other authors reported receiving grant/research support, consulting fees, and/or speaking fees from AbbVie and other companies that market biologics.

[email protected]