Background/Purpose: PsA is a chronic immune-mediated inflammatory disease associated with psoriasis, peripheral arthritis, enthesitis, dactylitis, and spondylitis. Ixekizumab (IXE) is an IgG4 mAb that binds with high affinity and specificity to the proinflammatory cytokine IL-17A. Data are presented for the phase 3 trial (SPIRIT‑P1) with IXE treatment of patients (pts) with active PsA. The objective was to evaluate the efficacy and safety of IXE when used alone or in combination with concomitant conventional DMARDs (cDMARDs).

Methods: A total of 417 bDMARD-naive adult pts were randomly assigned 1:1:1:1 to subcutaneous administration of 80-mg IXE every 4 wks (Q4W) or every 2 wks (Q2W), each starting with a 160-mg dose at Wk 0; adalimumab (ADA) 40 mg Q2W (active comparator); or placebo (PBO) during the Double-Blind Treatment Period (DBTP; Wks 0-24). Of these pts, 267 were receiving a concomitant cDMARD at baseline, 149 were not, and 1 did not receive study drug; pts were stratified by cDMARD use, and were to remain on their cDMARD through the DBTP. At Wk 24, efficacy was evaluated by ACR response; and progression of structural damage was assessed by the modified Total Sharp Score (mTSS). Safety assessments included the percentage of pts experiencing treatment‑emergent adverse events (TEAEs), serious adverse events (SAEs), and discontinuations due to adverse events (AEs). Efficacy analyses were conducted on the Intent‑to‑Treat Population, defined as all randomly assigned pts; safety analyses were conducted on the Safety Population, defined as all randomly assigned pts who received at least 1 dose of study drug. Fisher’s test was used for treatment comparisons in ACR and AE data, and an analysis of covariance model was used for mTSS data. Missing values were imputed by nonresponder imputation for ACR data and by linear extrapolation for mTSS data.  

Results: At Wk 24, compared with pts receiving PBO, significantly more pts receiving IXEQ4W or IXEQ2W (with/without concomitant cDMARD) achieved ACR20/50/70 responses (see Table for ADA results). Pts receiving IXEQ2W (with/without concomitant cDMARD) or IXEQ4W or ADA (with concomitant cDMARD) showed significantly less progression in mTSS from baseline compared with pts receiving PBO (Table). No treatment-by-subgroup effects were observed for ACR20/50/70 or mTSS (Table footnotes). In pts receiving concomitant cDMARDs, significantly more pts receiving IXE or ADA experienced ≥1 TEAE, compared with pts receiving PBO; the percentages of pts with SAEs or discontinuations due to an AE were comparable among treatment groups (Table).  

Conclusion: IXE demonstrated efficacy in improvement of PsA signs and symptoms and structural inhibition in bDMARD‑naive pts with/without concomitant cDMARD use. With concomitant cDMARD use, although significantly more pts receiving IXE or ADA experienced ≥1 TEAE, compared with pts receiving PBO, the frequency of SAEs and discontinuations due to an AE were comparable among all treatment group.