Background/Purpose: PsA has a negative impact on patients’ quality of life, physical function, and work productivity. Ixekizumab (IXE) is an IgG4 mAb that binds with high affinity and specificity to the proinflammatory cytokine IL-17A. In this phase 3 trial (SPIRIT P1), previously reported results showed that IXE treatment resulted in significant improvements (compared with placebo [PBO]) at Week [Wk] 24 in the patient‑reported outcome (PRO) measures of HAQ – Disability Index (HAQ-DI), Short Form-36 Health Survey Physical Component Summary (SF-36 PCS), European Quality of Life 5 Dimensions Visual Analog Scale (EQ-5D VAS), and Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP; presenteeism, work productivity, and activity impairment).The objective was to evaluate whether an effect of IXE on improvement of PROs is also observed at Wk 52.  

Methods: A total of 417 biologic DMARD (bDMARD)-naive patients (pts) with active PsA were randomly assigned 1:1:1:1 to subcutaneous administration of either 80 mg IXEQ4W or IXEQ2W, each with a 160 mg starting dose at Wk 0; adalimumab [ADA] 40 mg Q2W (active comparator); or PBO in the Double-Blind Treatment Period (DBTP; Wks 0 through 24). Of these pts, 381 continued into the Extension Period (EP; Wks 24-52). PBO- and ADA‑treated pts were randomly re-assigned (1:1) to 80 mg IXEQ4W or IXEQ2W at Wk 16 (inadequate responders) or Wk 24; ADA-treated pts started IXE after an 8-wk wash-out period at Wk 24 (inadequate responders) or Wk 32. Investigators were blinded as to criteria for inadequate response. Analyses for the EP were conducted on the EP Population, defined as all pts who received at least 1 dose of study drug during the EP. Missing values were imputed by nonresponder imputation for categorical data and modified baseline observation carried forward for continuous data.  

Results: Baseline demographics and clinical characteristics were generally similar between treatment groups; population mean baseline (Wk 0) scores for HAQ-DI, SF-36 PCS, and EQ-5D VAS (Table) indicated impaired physical function and quality of life. Physician‑assessed clinical efficacy was shown by 69% of pts treated with IXE for 52 wks achieving ACR20 response. Pts receiving IXE (Q4W or Q2W) for 52 wks reported similar improvements in HAQ-DI, SF‑36, EQ-5D VAS, and WPAI‑SHP (presenteeism, work productivity, and activity impairment) (Table) as reported at Wk 24, and the percentage of IXE pts with improvement from baseline HAQ-DI score ≥0.35 achieving minimally clinically important difference for HAQ‑DI was sustained at Wk 52 (Table) compared with Wk 24. At Wk 52, pts receiving ADA/IXE also showed similar improvements in ACR20 response and most PRO measures (Table) to those observed at Wk 24.  

Conclusion:   IXE provided sustained improvement through 52 wks in physical function, quality of life, and work productivity in bDMARD-naive pts with active PsA.