FRI0379\u2005LONG-TERM EVALUATION OF SECUKINUMAB 150 MG IN ANKYLOSING SPONDYLITIS: 5-YEAR END-OF-STUDY EFFICACY AND SAFETY RESULTS FROM A PHASE 3 TRIAL

Abstract

Background Evaluation of long-term efficacy and safety for treatments for ankylosing spondylitis (AS) is important. Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, has shown significant and sustained improvement in the signs and symptoms of AS through 3 years in the MEASURE 2 study (NCT01649375).1 Objectives We report the 5-year end-of-study results of subcutaneous (s.c.) secukinumab 150 mg in the MEASURE 2 study. Methods AS patients (pts; N = 219) were randomised to receive s.c. secukinumab 150 mg, 75 mg or placebo at baseline, Weeks (Wks) 1, 2 and 3 and every 4 wks from Wk 4. At Wk 16, placebo-treated pts were re–randomised to receive secukinumab 150/75 mg. Efficacy results are reported for pts initially randomised to secukinumab 150 mg and those who switched from placebo to secukinumab 150 mg at Wk 16 (N = 106). An optional dose escalation from secukinumab 75 mg to 150 mg was initiated beginning Wk 140. Outcome measures at Wk 260 included ASAS20/40, BASDAI50, BASMI, BASFI, SF-36 PCS and ASAS partial remission. Analyses stratified by anti-TNF status (anti–TNF-naïve and anti-TNF inadequate response [IR]) were performed. Safety analysis included all pts who received ≥1 dose of secukinumab. Results are reported as observed. Results The retention rate to Wk 260 was 77% (82/106) for secukinumab 150 mg. Sustained efficacy was observed with secukinumab 150 mg across all endpoints through 5 years (Table). Improvements were maintained regardless of prior exposure to anti–TNF therapy with greater responses in anti–TNF-naïve pts. A total of 49 pts on secukinumab 75 mg (46.7%) escalated dose to 150 mg after Wk 140; efficacy responses improved in pts whose dose was escalated. Over the entire study period, the mean exposure (±SD) to secukinumab was 1459.1 ± 597.8 days. Exposure-adjusted incidence rates (per 100 pt-years) with any secukinumab dose for selected adverse events were: Candida infections (1.0), Crohn’s disease (0.5), major adverse cardiovascular events (0.7), uveitis (0.5), and malignant/unspecified tumours (0.5). Conclusion Secukinumab 150 mg provided sustained improvement in the signs, symptoms, and physical function in pts with AS through 5 years of treatment. The safety profile of secukinumab remained consistent with previous reports.1–3 References [1] Marzo-Ortega, et al. RMD Open. 2017;3:e000592; 2. Marzo-Ortega, et al. Ann Rheum Dis. 2016;75:812–3; 3. Baraliakos X,et al. Clin Exp Rheumatol2017. Disclosure of Interests Helena Marzo-Ortega Grant/research support from: Janssen, Novartis and Pfizer, Consultant for: AbbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Speakers bureau: AbbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Joachim Sieper Consultant for: Abbvie, Böhringer Ingelheim, Janssen, Lilly, Merck, Mylan, Novartis, Pfizer, UCB., Speakers bureau: Abbvie, Böhringer Ingelheim, Janssen, Lilly, Merck, Mylan, Novartis, Pfizer, UCB., Alan Kivitz Shareholder of: Novartis, Consultant for: Abbvie, Janssen, Pfizer, UCB, Genzyme, Sanofi, Regeneron, Boehringer Ingelheim, Sun Pharma Advanced Research, Flexion., Paid instructor for: Celgene, Horizon, Merck, Novartis, Pfizer, Genzyme, Sanofi, Regeneron, Speakers bureau: Celgene, Horizon, Merck and Genetech, Flexion, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Martin Cohen Consultant for: AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sandoz, Sanofi and UCB, Speakers bureau: AbbVie, Amgen, Celgene, Janssen, Merck, Novartis and Pfizer, Karel Pavelka: None declared, Eumorphia Maria Delicha Employee of: Novartis, Anna Stefanska Shareholder of: Novartis, Employee of: Novartis, Hanno Richards Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, Susanne Rohrer Shareholder of: Novartis, Employee of: NovartisTable Efficacy Endpoints with Secukinumab 150 mg at Week 260 (5 year) Variable Secukinumab 150 mg1 Total N = 106 Anti–TNF-naïve N = 66 Anti–TNF-IR N = 40 ASAS202 69.9 (83) 73.7 (57) 61.5 (26) ASAS402 54.2 (83) 63.2 (57) 34.6 (26) ASAS-Partial Remission2 25.3 (83) 28.1 (57) 19.2 (26) BASDAI502 53.0 (83) 56.1 (57) 46.2 (26) BASMI3 -0.7±1.2 (80) - - BASFI3 -2.8±2.6 (83) - - SF-36 PCS3 8.0±8.5 (79) 8.5±8.9 (56) 6.8±7.4 (23) Data are reported as observed; 1Includes placebo switchers; 2% responders (n); 3mean change from baseline ± SD (n); IR, inadequate response; N, total number of randomised patients; n, number of evaluable patients; TNF, tumour necrosis factor