Background/Purpose: Biologic therapy is recommended in patients with active ankylosing spondylitis (AS) despite adequate trial of NSAIDs. Biologic treatment in AS are currently limited to TNF and IL-17A inhibitors (IL-17Ai). It is unknown whether there are predictors of AS patients who only respond to 1 of these mechanisms of action or respond to switching from TNF-blocker to IL-17Ai. This post-hoc analysis evaluated whether patients who did not respond to TNF inhibitor adalimumab (ADA) but did subsequently respond to IL-17Ai ixekizumab (IXE) differed from those that responded to both ADA and subsequent IXE.

Methods: The analysis included patients from the phase-3 COAST-V trial in bio-naive patients with active AS (BASDAI ≥4 and back pain ≥4 on VAS of 0-10). There were 341 patients randomized 1/1/1/1 to IXE 80 mg/2 weeks (wks) (Q2W), IXE 80 mg/4 wks (Q4W), ADA 40 mg Q2W (reference arm), and placebo (PBO) for the 16-week blinded-treatment period. Of these, 329 entered the dose double-blind extended treatment period (wks 16 to 52). Those who received PBO or ADA were re-randomized to receive IXE 80 mg Q4W or Q2W. Patients were stratified as responders or non-responders based on their Assessment of Spondyloarthritis International Society (ASAS) 40 response at wks 16 and 52. Data for the 2 IXE dose groups were pooled.

Results: Overall, more patients responded to IXE than ADA at wk 16.¹ Based on ASAS40 response at wks 16 and at wk 52, 30.9% of patients responded to both initial ADA and subsequent IXE, 23.5% of patients did not respond to initial ADA but did respond to subsequent IXE, 45.9% of patients responded to IXE at both time points, and 12.3% of patients did not respond to IXE at wk 16 but did so at wk 52. Across the groups, patients were of similar age and predominantly males, though there were proportionally more women among those who did not respond to either ADA or IXE at wk 16. No meaningful differences were observed in disease duration or baseline clinical disease activity. However, ADA non-responders at wk 16/IXE responders at wk 52 had numerically lower baseline (mean[SD]) C-reactive protein (11.2 [11.2]), lower magnetic resonance imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) scores of the spine (11.6 [12.1]), and lower MRI SPARCC score of the sacroiliac joints (1.1 [2.2]) than ADA responders at wk16/IXE responders at wk 52 patients (16.0 [17.1], 24.6 [32.6], and 5.5 [9.8]), respectively (Table 1).

Conclusion: In this analysis, patients who did not respond to ADA but subsequently responded to IXE exhibited overall lower levels of inflammation, as measured by CRP and MRI of the spine or sacroiliac joints, compared with patients who responded on ADA and also after switching to IXE. Along with comparative findings in patients who continuously received IXE and responded at both wks 16 and 52 or wk 52 only, these data indicate that IXE is efficacious in patients with active AS irrespective of inflammation level, assessed by CRP and MRI. Alternatively, lower baseline inflammation may be a predictor of delayed response.

Reference: 1van der Heijde et. al. Lancet 2018

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-features-of-patients-with-active-ankylosing-spondylitis-who-did-not-respond-to-adalimumab-but-responded-to-ixekizumab-a-post-hoc-analysis/