Session Information
Date: Tuesday, November 10, 2015
Title: Spondylarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment Poster III: Therapy
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Secukinumab, an anti–interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) in 2 Phase 3, randomized, double-blind, placebo (PBO)-controlled studies, MEASURE 1 (NCT01358175) and MEASURE 2 (NCT01649375).1,2We report the safety of secukinumab in AS through ≥52 weeks (wks) using pooled data from these 2 studies.
Methods: Both studies enrolled patients (pts) with active AS with radiological evidence fulfilling the modified New York Criteria. In MEASURE 1, 371 pts were randomized to secukinumab or PBO. Pts on secukinumab received 10 mg/kg intravenously (IV) at baseline (BL), Wk 2 and 4, followed by 75 or 150 mg subcutaneously (SC) every 4 wks (q4w) from Wk 8. PBO was given according to the same IV to SC schedule. In MEASURE 2, 219 pts were randomized to receive SC secukinumab (75 or 150 mg) or PBO at BL, Wk 1, 2, and 3, and q4w starting from Wk 4. At Wk 16, PBO pts were re-randomized to receive secukinumab 150 or 75 mg SC q4w. Anti-drug antibodies (ADAs) were assessed using a Meso Scale Discovery bridging assay. Safety data were pooled at the pt level, with a data cut-off of Wk 52 visit of the last pt enrolled in each study.
Results: 571 pts received ≥1 dose of secukinumab (691.1 pt-years of exposure). Baseline demographic and disease characteristics were well-balanced in the pooled secukinumab and PBO populations. The incidence of adverse events (AEs)/serious AEs (SAEs) during the 16-wk PBO-controlled period was 65.7/3.3% and 58.7/4.1% in the secukinumab and PBO groups, respectively. Exposure-adjusted AE/SAE rates across the entire safety period (mean exposure: secukinumab, 442.1 days; PBO, 118.5 days) were 206.8/7.9 and 359.5/12.8 per 100 pt-years with secukinumab and PBO, respectively; 27 (4.7%) pts receiving secukinumab and 11 (5.6%) receiving PBO discontinued due to AEs during the study. Three deaths were reported: 1 suicide (PBO); 1 due to respiratory failure (IV→75 mg) and 1 due to an acute myocardial infarction (75 mg), both in pts with multiple cardiovascular risk factors. Nasopharyngitis was the most frequent AE with secukinumab (11.2% with secukinumab vs 6.1% with PBO during the 16-wk PBO-controlled period; 17.9 vs 19.5 per 100 pt-years during the entire study period). The incidence of inflammatory bowel/Crohn’s disease, Candidainfections, neutropenia, major adverse cardiac events, and malignancy was low with secukinumab (Table). Uveitis AEs were reported in 7 (1.2%) pts on secukinumab and 2 (1.0%) on PBO. Treatment-emergent ADAs were detected in 2 (0.3%) pts, with no associated loss of efficacy. There were no suicidality-related AEs with secukinumab.
Conclusion: Secukinumab was well-tolerated in pts with active AS, with a low incidence of SAEs and discontinuations due to AEs.
References:
- Baeten D, et al. Arthritis Rheumatol 2014; 66 (11Suppl):S360
- Sieper J, et al. Arthritis Rheumatol. 2014;66(11Suppl):S232
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Table: Summary of pooled safety across the MEASURE 1 and MEASURE 2 studies |
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Placebo-controlled period: 16 wks |
Entire safety period:
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Any secukinumab dose N=394 |
Placebo N=196 |
Any secukinumab dose N=571a |
Placebo N=196 |
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Exposure (days), mean (SD) |
112.1 (14.3) |
108.6 (22.5) |
442.1 (142.8) |
118.5 (32.8) |
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Minimum–maximum exposure (days) |
8-195 |
1-176 |
8-757 |
1-206 |
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Number of pts with event (%) |
Number of events per 100 pt-years (95% CI) |
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Any AE |
259 (65.7) |
115 (58.7) |
206.8 (188.4- 226.4) |
359.5 (297.6-430.5) |
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Any SAE |
13 (3.3) |
8 (4.1) |
7.9 (5.9-10.3) |
12.8 (5.5-25.2) |
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AEs of special Interest |
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Infections and infestations Candida infections |
121 (30.7) 2 (0.5) |
35 (17.9) 0 (0.0) |
68.8 (61.2-77.0) 0.9 (0.3-1.9) |
63.8 (44.7-88.4) 0.0 (0.0-5.8) |
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IBD Crohn’s disease |
3 (0.8) 2 (0.5) |
0 (0.0) 0 (0.0) |
1.2 (0.5-2.3) 0.7 (0.2-1.7) |
0.0 (0.0-5.8) 0.0 (0.0-5.8) |
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MACEb |
1 (0.3) |
0 (0.0) |
0.4 (0.1-1.3) |
0.0 (0.0-5.8) |
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Malignancy |
1 (0.3) |
1 (0.5) |
0.6 (0.2-1.5) |
1.6 (0.0-8.8) |
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Neutropenia |
10 (2.5) |
1 (0.5) |
4.1 (2.7-5.9) |
1.6 (0.0-8.8) |
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aIncludes PBO pts re-randomized to secukinumab; bAdjudicated events AE, adverse event; CI, confidence interval; IBD, inflammatory bowel disease; MACE, major adverse cardiac events; pts, patients; SAE, serious adverse event; SD, standard deviation; wks, weeks |
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To cite this abstract in AMA style:
Deodhar AA, Baeten D, Sieper J, Porter B, Widmer A, Richards H. Safety and Tolerability of Secukinumab in Patients with Active Ankylosing Spondylitis: Pooled Safety Analysis of Two Phase 3, Randomized, Controlled Trials [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/safety-and-tolerability-of-secukinumab-in-patients-with-active-ankylosing-spondylitis-pooled-safety-analysis-of-two-phase-3-randomized-controlled-trials/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-and-tolerability-of-secukinumab-in-patients-with-active-ankylosing-spondylitis-pooled-safety-analysis-of-two-phase-3-randomized-controlled-trials/