Background/Purpose : There is a lack of validated outcome measures in non-psoriatic peripheral spondyloarthritis (pSpA). Therefore, a modified version of the minimal disease activity (mMDA)¹ was developed and validated. Identification of factors that predict long-term mMDA response in pSpA patients (pts) can facilitate decisions regarding treatment initiation and maintenance. The purpose of this analysis was to determine predictors of long-term mMDA response following adalimumab (ADA) treatment in pSpA pts from the ABILITY-2 study.

Methods : ABILITY-2² was a phase 3 randomized, double-blind trial evaluating the efficacy and safety of 40 mg ADA every other week versus placebo (PBO) over 12 weeks (wks) followed by open-label (OL) ADA for 144 wks in pts with pSpA. This post-hoc analysis included pts who received at least one dose of ADA during the PBO-controlled period or OL extension. The mMDA for pSpA was defined as achieving at least 5 out of the following 6 criteria: 1) TJC78 ≤1; 2) SJC76 ≤1; 3) pt pain visual analog scale (VAS) ≤ 15 of 100 mm; 4) pt global activity (PtGA) VAS ≤ 20 of 100 mm; 5) HAQ-DI ≤ 0.5; and 6) tender entheseal points ≤ 1 (Leeds Enthesitis Index [LEI] or Spondyloarthritis Research Consortium of Canada [SPARCC] Enthesitis Index). In this post hoc analysis, multiple logistic regression with stepwise variable selection was used to determine predictors of long-term (yrs 1-3) and sustained (defined as mMDA for at least 24 consecutive wks) mMDA responses. Variable selection of baseline (BL) pt demographics and disease characteristics were performed with and without mMDA response at after 12 wks of ADA exposure (mMDA12) as a candidate.

Results : In pSpA pts treated with ADA, mMDA (5/6 LEI or SPARCC) was achieved by almost 41%, 49%, and 50% of pts at yrs 1, 2, and 3, respectively and sustained mMDA response was achieved by 42% of pts. Regardless of mMDA definition, achieving mMDA response after 12 wks of ADA exposure was a robust positive predictor of attaining both long-term mMDA at yrs 1-3 and sustained mMDA (Figure). In the model examining the BL predictors (model without mMDA12), age, BL enthesitis and BL BASDAI scores were most commonly selected as negative predictors for achieving long-term and sustained mMDA. Other selected predictors included BL dactylitis, physician’s global assessment, hsCRP, and male sex; however, these predictors were not consistently selected for all time points or sustained mMDA.

Conclusion : Early mMDA response is a stronger and more consistent predictor of long-term mMDA, whether at 1, 2, or 3 yrs or sustained over time, than BL characteristics. The 5/6 versions of mMDA could be an appropriate treatment target in pSpA pts.

References:

1.            Coates LC, et al., Ann Rheum Dis, 2016; 75:334.

2.            Mease PJ, et al., Arthritis Rheumatol, 2015; 67(4): p.914-23.