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Abstract
Background Ixekizumab (IXE) is an IgG4 monoclonal antibody that binds with high affinity and specificity to the proinflammatory cytokine IL-17A. In this phase 3 study (SPIRIT-P1), IXE was superior to placebo (PBO) in achieving American College of Rheumatology 20 (ACR20) response at Week 24 in biologic disease-modifying antirheumatic drug-naive (bDMARD-naive) patients with active psoriatic arthritis (PsA)1.
Objectives To evaluate efficacy and safety of IXE over 52 weeks in patients with active PsA.
Methods A total of 417 bDMARD-naive patients with active PsA were randomized 1:1:1:1 to IXE 80 mg once every 4 weeks (Q4W) or once every 2 weeks (Q2W) including a 160 mg starting dose, to 40 mg adalimumab (ADA), or to PBO (all subcutaneous dosing) during the Double-Blind Treatment Period (DBTP: Weeks 0 to 24). Of these, 381 patients completed the DBTP and entered the Extension Period (EP: Weeks 24 to 52) where they were assigned to 80 mg IXE Q4W or Q2W. Patients randomized to IXE at Week 0 continued the same dose regimen in the EP. Patients randomized to PBO or ADA at Week 0 were re-randomized (1:1) to 80 mg IXE Q4W or Q2W at Week 16 (inadequate responders) or 24. Those patients who initially received PBO started IXE at Week 16 or 24; patients who initially received ADA started IXE at Week 24 or 32 after an 8 week wash out period. Efficacy measures included ACR20/50/70 response, Health Assessment Questionnaire-Disability Index (HAQ-DI) Score, Disease Activity Score 28 diarthrodial joint count based on C-reactive protein (DAS 28-CRP), Psoriasis Area and Severity Index 75, 90, 100 (PASI 75/90/100), Leeds Enthesitis Index (LEI), and Leeds Dactylitis Index-Basic (LDI-B). Efficacy and safety were analyzed using the EP population defined as all patients who received at least 1 dose of study drug in the EP. Missing values were imputed by nonresponder imputation for categorical data and modified baseline observation carried forward for continuous data.
Results A total of 304 patients completed the EP. Efficacy and safety results in the EP population are summarized in Table 1. Improvements from baseline in ACR20/50/70, HAQ-DI, DAS 28-CRP, PASI 75/90/100, LEI and LDI-B were observed at Week 52. The frequency of treatment-emergent adverse events (AEs) in the EP was similar to that observed in the DBTP; the majority were mild or moderate in severity. Serious AEs occurred in 12 patients and no deaths occurred in the EP population.
Conclusions IXE demonstrated clinically significant improvement in signs and symptoms of PsA including arthritis, dactylitis and enthesitis as well as skin manifestations across treatment groups in the EP. The safety profile of IXE observed in the EP was similar to that observed in the DBTP and other phase 3 studies of IXE in patients with plaque psoriasis (UNCOVER studies).
Philip J. Mease et al. 2015 ACR/ARHP Annual Meeting, 6–11 November, San Francisco, CA 2015; [abstract 977].
Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer; UCB Pharma, Consultant for: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Pfizer, UCB Pharma, M. Okada Grant/research support from: Lilly, Consultant for: Lilly, Speakers bureau: Santen Pharmaceutical, Mitsubishi Tanabe Pharma, Pfizer, Abbott Japan, M. Kishimoto Consultant for: Lilly, C. Shuler Shareholder of: Lilly, Employee of: Lilly, H. Carlier Shareholder of: Lilly, Employee of: Lilly, C.-Y. Lin Shareholder of: Lilly, Employee of: Lilly, J. Mou Shareholder of: Lilly, Employee of: Lilly, S. Moriarty Shareholder of: Lilly, Employee of: Lilly, C. Lee Shareholder of: Lilly, Employee of: Lilly, D. Gladman Grant/research support from: AbbVie, Amgen, Celgene, Janssen, Novartis, UCB Pharma, Consultant for: Abbvie, Amgen, BMS, Celgene, Lilly, Novartis, Pfizer, UCB