Objectives To describe the safety profile of secukinumab, an anti–interleukin-17A monoclonal antibody, in patients (pts) with psoriatic arthritis (PsA) treated in phase 3 studies.
Methods Safety data from two randomized, double-blind, placebo (PBO)-controlled, phase 3 studies in pts with active PsA, FUTURE 1 (NCT01392326) and FUTURE 2 (NCT01752634), were pooled. In FUTURE 1, 606 pts were randomized to secukinumab or PBO. Pts on secukinumab received 10 mg/kg i.v at baseline, Week (Wk) 2, and 4, followed by 150 or 75 mg s.c. every 4 wks from Wk 8. PBO was given according to the same i.v. and s.c. schedule. In FUTURE 2, 397 pts were randomized to receive s.c. secukinumab (300, 150, or 75 mg) or PBO at baseline, Wk 1, 2, 3, 4, and every 4 wks thereafter. At Wk16, PBO pts with ≤20% reduction in both tender and swollen joint count (nonresponders) were re-randomized to receive secukinumab 150 or 75 mg s.c. in FUTURE 1, and secukinumab 300 or 150 mg s.c. in FUTURE 2; responders were re-randomized at Wk 24. Anti-drug antibodies (ADAs) were assessed using a Meso Scale Discovery bridging assay with a stepwise approach for screening, confirmation and titration. All randomized pts were included in the pooled safety analysis.
Results 974 pts received ≥1 dose of secukinumab (955 pt-years of exposure). Baseline demographics, disease/medical history and concomitant medications were similar between the pooled secukinumab and PBO populations. During the 16-wk PBO-controlled period, adverse events (AEs)/serious AEs (SAEs) were reported in 58.9%/3.4% and 58.3%/4.0% of pts in the pooled secukinumab and PBO groups, respectively. Exposure-adjusted AE/SAE incidence rates across the entire safety period (mean/max exposure: 358.1/721 days secukinumab; 128.6/233 days PBO) were 210.3/9.0 and 319.6/13.6 per 100 pt-years with secukinumab and PBO, respectively; 25 (2.6%) pts receiving secukinumab discontinued due to AEs during this period vs. 14 (4.7%) with PBO. Nasopharyngitis and upper respiratory tract infection (URTI) were the most frequent AEs with secukinumab and PBO in both the PBO-controlled period and throughout the entire safety period. There was one death due to intracranial hemorrhage in a pt with a history of CV disease who received secukinumab. The incidence of inflammatory bowel disease (IBD)/Crohn's, Candida infections, neutropenia, MACE and malignancy was low with secukinumab (Table). Injection site reactions with secukinumab were observed in 26 (2.7%) pts vs. 3 (1.0%) with PBO. Treatment-emergent ADAs were detected in 1 (0.1%) pt, with no associated loss of efficacy.
Conclusions Secukinumab was well-tolerated in pts with active PsA, with a low incidence of SAEs and discontinuations due to AEs, and a low potential for immunogenicity.
Acknowledgements Medical writing support was provided by Chris Strutynskyj-Stannard at Seren Communications (Tytherington, UK), and was funded by Novartis.
Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, Consultant for: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Covagen, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, Speakers bureau: AbbVie, Amgen, Biogen Idec, BMS, Crescendo, Janssen, Lilly, Pfizer, and UCB, I. McInnes Consultant for: Novartis, Amgen, Janssen, BMS, Pfizer, UCB, Abbvie, Celgene, and Lilly, H. Richards Employee of: Novartis, L. Pricop Shareholder of: Novartis, Employee of: Novartis, A. Widmer Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis