Background/Purpose: Multiple biologic DMARD (bDMARD) treatments are available for PsA, but there is limited research that compares the safety and efficacy of these treatments. Head-to-head (H2H) studies may improve the strength of PsA treatment guidelines and provide valuable guidance to physicians in selecting optimal treatment.¹ SPIRIT-H2H, the first completed H2H superiority study in active PsA, showed superiority of ixekizumab (IXE), an IL-17A antagonist, over adalimumab (ADA), a TNF inhibitor, on a combined endpoint at Week 24.² Here we report the Week 24 efficacy of IXE and ADA in subgroups defined by baseline disease characteristics.

Methods: SPIRIT-H2H (NCT03151551) is a 52-week, multicenter, open-label, blinded assessor study in bDMARD-naïve patients who were inadequate responders to conventional synthetic DMARD (csDMARD) with active PsA (≥3 tender joint count [TJC] and ≥3 swollen joint count [SJC]) and plaque psoriasis (body surface area [BSA] ≥3%). All patients met Classification Criteria for PsA. Patients were randomized 1:1 to IXE or ADA on-label dosing based on presence/absence of moderate-to-severe psoriasis (BSA ≥10% + Psoriasis Area and Severity Index [PASI] ≥12 + static Physician Global Assessment [sPGA] ≥3). A blinded assessor measured TJC, SJC, enthesitis, dactylitis, PASI, sPGA, BSA, and fingernail psoriasis. This post hoc subgroup analysis assessed efficacy in patients with baseline enthesitis (presence/absence), dactylitis (presence/absence), fingernail psoriasis (presence/absence), BSA (10% cutoff), and CRP (6 mg/L cutoff). Week 24 outcomes were compared between IXE and ADA at ACR20/50/70 responses and minimal disease activity (MDA). Missing data were imputed by nonresponder imputation. While the post hoc analysis was not controlled for multiplicity, all comparisons were analyzed by Fisher’s exact test.

Results: The Table summarizes Week 24 efficacy outcomes by subgroup. There were no statistical differences between IXE and ADA at ACR20 and ACR50 response rates across all of the examined subgroups. ACR70 responses were comparable across subgroups, except significantly more IXE-treated patients with baseline fingernail psoriasis achieved ACR70 than ADA-treated patients (p=.02). Significantly more IXE- than ADA-treated patients achieved MDA-6 in subgroups with baseline enthesitis (p=.002), without dactylitis (p=.015), with fingernail psoriasis (p< .001), CRP≤6 mg/L (p=.046), and BSA ≥10% (p=.01). All other subgroups analyzed demonstrated comparable efficacy on IXE and ADA.
A limitation of this analysis is that it was completed post hoc, not controlled for multiplicity, and patients were not stratified by these baseline disease characteristics.

Conclusion: IXE and ADA are associated with comparable efficacy in the signs and symptoms of PsA in patient subgroups defined by baseline enthesitis, dactylitis, fingernail psoriasis, BSA, and CRP.

References:

1. Singh JA, et al. Arthritis Rheumatol. 2019 Jan;71(1):5-32.
2. Available at: https://clinicaltrials.gov/ct2/show/results/NCT03151551?term=spirit-h2h&rank=1

Table

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/improvement-in-the-signs-and-symptoms-of-psoriatic-arthritis-with-ixekizumab-compared-to-adalimumab-in-patient-subgroups-defined-by-baseline-disease-characteristics/