Background/Purpose: SKIPPAIN (NCT03136861) is the first randomized controlled study involving a biological disease modifying antirheumatic drug, with spinal pain as the primary endpoint as early as Week (Wk) 8 in a broad population of patients (pts) with axial spondyloarthritis (axSpA; ankylosing spondylitis [AS] and non-radiographic [nr]-axSpA). Clinical studies in axSpA routinely use composite measures of disease activity to assess treatment effect, despite pain being the most troubling symptom for pts^1–2. Here we present the 24-wk results from the SKIPPAIN study that evaluated the efficacy and safety of secukinumab (SEC) in reducing spinal pain and disease activity following a step-up dosing approach.

Methods: SKIPPAIN was a 24-wk, randomized, double-blind, multicenter, placebo (PBO)-controlled phase 3b study. Pts (aged ≥18 years) diagnosed with active disease defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4 and average spinal pain numerical rating scale (NRS) score >4 at baseline and inadequate response to ≥2 NSAIDs ≥4 wks were enrolled. Pts were randomized (3:1) to receive subcutaneous SEC 150 mg or PBO wkly followed by every 4 wks (q4w) starting at Wk 4. At Wk 8, PBO pts were re-randomized to SEC 150 or 300 mg q4w up to Wk 24. Pts originally randomized to SEC 150 mg, were further classified as responders (spinal pain NRS score < 4) or non-responders (spinal pain NRS score ≥4) at Wk 8. Responders were re-assigned to continue double-blind treatment with 150 mg q4w up to Wk 24 (Arm A1). Non-responders were re-randomized to receive double-blind treatment with either 150 (Arm A2) or a step-up dose of 300 mg (Arm A3) q4w up to Wk 24. Primary endpoint was the proportion of pts achieving an average spinal pain score < 4 on a 0–10 NRS with SEC vs PBO at Wk 8. Change in spinal pain NRS and Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) scores at Wk 24 were exploratory endpoints.

Results: A total of 380 axSpA pts (269 [70.8%] AS and 111 [29.2%] nr-axSpA) were randomized to SEC 150 mg (N=285) or placebo (N=95). Primary endpoint of the study was met (proportion of spinal pain NRS (average) score responders: 32% vs 20% with an odds ratio [95% CI] of 1.9 [1.1, 3.3] favoring SEC vs PBO; P < 0.05). At Wk 24, further reductions in spinal pain were observed across treatment groups especially in those initially randomized to placebo and switched to active drug at Wk 8. Pronounced improvements were also observed in other disease activity measurements such as ASDAS-CRP score (Table and Figure). Of note, a numerically higher proportion of pts achieved ASDAS low disease activity at Wk 24 after SEC dose escalation at Wk 8 (Arm A3) as compared to those who remained on the same dose (Arm A2). No new or unexpected safety signals were reported.

Conclusion: Conclusion: SEC provided rapid, significant improvement in spinal pain and led to low disease activity in pts with axSpA. SEC dose escalation might be beneficial for pts not responding fully to the starting dose.

References:

1. Danve A & Deodhar A. Clin Rheumatol. 2019; 38:625-34.
2. Strand V, Singh JA. J Clin Rheumatol. 2017;23:383‐391.

Table. Spinal pain and ASDAS-CRP scores at Wks 8 and 24

Figure. Efficacy results at Wk 24

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/secukinumab-provides-significant-improvement-of-spinal-pain-and-lowers-disease-activity-in-patients-with-axial-spondyloarthritis-24-week-results-from-a-randomized-controlled-phase-3b-trial/