Background Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease associated with psoriasis, peripheral arthritis, enthesitis, dactylitis, and spondylitis. PsA has a negative impact on patients' quality of life, physical function, and work productivity. Ixekizumab (IXE) is an IgG4 monoclonal antibody 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 Health Assessment Questionnaire – 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, activity impairment).
Objectives To evaluate whether an effect of IXE on improvement of PROs is also observed at Wk 52.
Methods A total of 417 biologic disease-modifying antirheumatic drug (bDMARD)-naive patients with active PsA were randomly assigned 1:1:1:1 to subcutaneous administration of 80-mg IXE every 4 wks (Q4W) or 2 wks (Q2W), 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 patients, 381 continued into the Extension Period (EP; Wks 24 through 52). PBO- and ADA-treated patients were randomly re-assigned (1:1) to 80 mg IXEQ4W or IXEQ2W at Wk 16 (inadequate responders) or Wk 24; ADA-treated patients 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 patients 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 patients treated with IXE for 52 wks achieving American College of Rheumatology (ACR) 20 response. Patients 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, activity impairment) (Table) to Wk 24 results, and the percentage of IXE patients 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, patients receiving ADA/IXE also showed similar improvements in ACR20 response and most PRO measures (Table) to Wk 24 results.
Conclusions IXE provided sustained improvement through 52 wks in physical function, quality of life, and work productivity in bDMARD-naive patients with active PsA.
Disclosure of Interest A. Gottlieb Grant/research support from: Centocor (Janssen), Amgen, Abbott (AbbVie), Novartis, Celgene, Pfizer, Lilly, Coronado, Levia, Merck, Xenoport, Dermira, Consultant for: Amgen, Astellas, Akros, Centocor (Janssen), Celgen, Bristol Myers Squibb, Beiersdorf, Abbot Labs (AbbVie), TEVA, Actelion, UCB, Novo Nordisk, Novartis, Dermipsor, Incyte, Pfizer, Canfite, Lilly, Coronado, Vertex, Karyopharm, CSL Behring Biotherapies for Life, Glaxo Smith Kline, Xenoport, Catabasis, Meiji Seika Pharma, Takeda, Mitsubishi Tanabe Pharma Development America, Genentech, M. E. Husni Consultant for: Lilly, Novartis, Abbvie, Celgene, Bristol Myers Squibb, Amgen, Janssen, UCP Pharma, C. Shuler Shareholder of: Lilly, Employee of: Eli Lilly and Company, R. Burge Shareholder of: Lilly, Employee of: Eli Lilly and Company, C.-Y. Lin Shareholder of: Lilly, Employee of: Eli Lilly and Company, C. Lee Shareholder of: Lilly, Employee of: Eli Lilly and Company, D. Gladman Grant/research support from: AbVie, Amgen, Celgene, Janssen, Novartis, UCP Pharma, Consultant for: Abbvie, Amgen, BMS, Celgene, Lilly, Novartis, Pfizer, UCB