Randomized Controlled Trial of Adalimumab in Patients with Nonpsoriatic Peripheral Spondyloarthritis

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SCIENCE
Randomized Controlled Trial of Adalimumab in Patients with Nonpsoriatic Peripheral Spondyloarthritis
Key Take-Away: 
  • Adalimumab treatment improved physical function in patients with active nonpsoriatic peripheral SpA who exhibited an inadequate response or intolerance to NSAIDs.
  • A high percentage of patients receiving adalimumab achieved a PSpARC40 response as compared to patients receiving placebo at week 12.

The spondyloarthritides (SpA) refers traditionally to a group of interrelated diseases, which includes ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), inflammatory bowel disease (IBD)–related arthritis, and undifferentiated SpA (uSpA). The Assessment of Spondyloarthritis international Society (ASAS) classification criteria for peripheral SpA were meant to be applied to patients with an established diagnosis of SpA, peripheral arthritis (usually asymmetric or predominantly involving the lower limbs), enthesitis, and/or dactylitis. 

ABSTRACT: 
Background: 

The spondyloarthritides (SpA) refers traditionally to a group of interrelated diseases, which includes ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), inflammatory bowel disease (IBD)–related arthritis, and undifferentiated SpA (uSpA). The Assessment of Spondyloarthritis international Society (ASAS) classification criteria for peripheral SpA were meant to be applied to patients with an established diagnosis of SpA, peripheral arthritis (usually asymmetric or predominantly involving the lower limbs), enthesitis, and/or dactylitis.

However, majority of patients with peripheral SpA present with features typical of SpA, but their disease overall does not fit in any of these categories. These patients have been labeled as having uSpA and will probably benefit most from the new classification criteria for peripheral SpA. For example, the most cited study about a possible effect of sulfasalazine in patients with SpA included only patients with AS, PsA, or ReA. Anti–tumor necrosis factor (anti-TNF) therapy, including adalimumab, has been proven effective for the treatment of PsA (10–13). Patients with nonpsoriatic peripheral SpA may also benefit from anti-TNF therapy.

Rationale behind research

  1. Numerous studies proven that adalimumab has been effective for the treatment of PsA but patients with nonpsoriatic peripheral SpA may also benefit from anti-TNF therapy
  • Objective

To evaluate the efficacy and safety of adalimumab in patients with active nonpsoriatic peripheral spondyloarthritis (SpA)

Methods: 

 

Study outcomes 

  • Primary outcome: The proportion of patients achieving 40% improvement in disease activity according to Peripheral SpA Response Criteria (PSpARC40) at week 12. It was defined as >40% improvement from baseline (>20-mm absolute improvement on a visual analog scale) in patient’s global assessments of disease activity and pain, and >40% improvement in at least one of the following features: swollen joint and tender joint counts, total enthesitis count, or dactylitis count.
  • Secondary outcomes:
  • Physician’s global assessment of disease activity (0–100-mm VAS), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; scale 0–10), the Health Assessment Questionnaire modified for the Spondyloarthropathies (HAQ-S), and the Short-Form 36 version 2 (SF-36v2) Health Survey physical component summary (PCS) score.
  • Other variables analyzed at various time points included the enthesitis assessment, consisting of the Leeds Enthesitis Index (scale 0–6), SPARCC Enthesitis Index (scale 0–16), and MASES (scale 0–13), and the Ankylosing Spondylitis Disease Activity Score (ASDAS)
  • Frequency of AEs that began or worsened after treatment
  • Time-points
  • Efficacy: Baseline and every two weeks upto 12 weeks
Results: 

 

  • Baseline:
  • Percentage of patients with other clinical manifestations or features associated with SpA were similar in both groups at baseline, except that there were more patients with a history of preceding infection characteristic of ReA in the placebo group.
  • Mean age was higher in the adalimumab group, and the percentage of patients with a dactylitis count ≥1 was lower in the adalimumab group compared to placebo group.
  • Primary outcome:
  • At week 12, a great proportion of patients receiving adalimumab achieved PSpARC40 response compared to placebo patients (39% versus 20%; P =0.006)
  • The proportions of patients meeting the PSpARC20, PSpARC50, and PSpARC70 response levels at week 12 were also significantly greater in the adalimumab group compared to the placebo group
  • Mean improvements in some of the individual components of  PSpARC40 (patient’s global assessments of disease activity and pain, TJC, SJC, and total enthesitis count) were significantly greater with adalimumab treatment compared to placebo
  • Secondary outcome:
  • Improvement in physical function and health-related quality of life, as measured by the SF-36v2 PCS, was significantly greater in patients receiving adalimumab compared to those receiving placebo but no significant difference in the HAQ-S scores at week 12 was observed between the adalimumab and placebo groups.
  • Significant improvement was observed with adalimumab than placebo in the Leeds and SPARCC scores for enthesitis and total enthesitis count, but not in MASES
  • The overall incidence of any AE in the adalimumab group was similar to that in the placebo group
Conclusion: 

Treatment with adalimumab ameliorated the signs and symptoms of disease and improved physical function in patients with active nonpsoriatic peripheral SpA who exhibited an inadequate response or intolerance to NSAIDs, with a safety profile consistent with that observed in patients with AS, PsA, or other immune-mediated diseases.

These results suggest that the novel composite end point of the PSpARC40, which was developed specifically for this nonpsoriatic peripheral SpA population, performs well in discriminating the efficacy of the active drug from the placebo treatment in this population while enabling a comprehensive evaluation of disease activity. Previously published reports on the benefits of anti-TNF therapy in enthesitis, significant improvement in enthesitis was demonstrated following treatment with adalimumab, as indicated by the Leeds and SPARCC enthesitis indices but not by the MASES. These observations are consistent with the findings in a study by Paramarta et al, in which the BASDAI50 score (adalimumab 42% versus placebo 5%) and ASDAS inactive disease score (adalimumab 42% versus placebo 0%) showed significant improvements in those treated with placebo after 12 weeks of therapy. Furthermore, in the adalimumab group, significant improvement in function and health-related quality of life, as measured using the SF-36v2 PCS, was also observed.

Arthritis Rheumatol. 2015 Apr;67(4):914-23.
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