Abstract
Background/Aims
Pooled safety data have been reported with secukinumab in patients with psoriatic arthritis (PsA), ankylosing spondylitis (AS) and psoriasis (PsO). Here we report longterm safety data for secukinumab in patients with PsA, AS or PsO up to 5 years.
Methods
The integrated clinical trial safety dataset included data pooled from 28 randomised controlled clinical trials of secukinumab 300, 150 or 75 mg in PsO (11 Phase 3 and 8 Phase 4 trials), PsA (5 Phase 3 trials) and AS (4 Phase 3 trials), along with post-marketing safety surveillance data starting 26 December 2014, with a cut-off date of 25 December 2018. Adverse events were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥1 dose of secukinumab.
Results
A total of 12,637 patients (8,819, 2,678 and 1,140 patients with PsO, PsA and AS, with an exposure of 15,063.1, 5,984.6 and 3,527.2 patient-years, respectively) were included. The most frequent adverse event was upper respiratory tract infection and the EAIR per 100 patient-years for inflammatory bowel disease (IBD), malignancies and major adverse cardiac events (MACE) remained low. The EAIR per 100 patient-years for adverse events of special interest are reported in Table 1. The cumulative post-marketing exposure to secukinumab was estimated to be ∼285,811 patient-years across the approved indications. Post-marketing safety data showed cumulative reporting rates of 1.4, 0.3, 0.2 and 0.2 patienttreatment years for serious infections, malignancy, total IBD and MACE, respectively.
Conclusion
Secukinumab was well tolerated in this long-term analysis of patients with PsO, PsA and AS across clinical trials and post-marketing surveillance, with a safety profile consistent with previous reports (Deodhar, 2019). P191 Table 1:Selected adverse events of interest with secukinumab across pooled clinical trialsVariablePsOPsAASSEC N = 8,819SEC N = 2,678SEC N = 1,140Exposure (days),mean (SD)623.9 (567.7)816.2 (580.7)1130.1 (583.0)Death, n (%)14 (0.2)11 (0.4)9 (0.8)Selected adverse events of interest, EAIR (95% CI)Serious infectionsa1.4 (1.2-1.6)1.8 (1.5-2.2)1.2 (0.9-1.6)Candida infectionsb2.9 (2.7-3.2)1.5 (1.2-1.9)0.7 (0.5-1.1)IBDc0.01 (0.0-0.05)0.03 (0.0-0.1)0.03 (0.0-0.2)Crohns diseasec0.1 (0.05-0.2)0.1 (0.04-0.2)0.4 (0.24-0.7)Ulcerative colitisc0.1 (0.08-0.2)0.1 (0.04-0.2)0.2 (0.1-0.5)MACEd0.4 (0.3-0.5)0.4 (0.3-0.6)0.7 (0.4-1.0)Uveitisc0.01 (0.0-0.05)0.1 (0.04-0.2)1.2 (0.9-1.7)Malignancye0.9 (0.7-1.0)1.0 (0.77-1.3)0.5 (0.3-0.8)aRates for system organ class;bRates for high level term;cRates for preferred term (PT; IBD for unspecified IBD);dRates for Novartis MedDRA Query term;eRates for standardised MedDRA Query term - ‘malignancies and unspecified tumour’. AS, ankylosing spondylitis; CI, confidence interval; EAIR, exposure-adjusted incidence rate per 100 patient-years; IBD, inflammatory bowel disease; MACE, major adverse cardiac events; MedDRA, Medical Dictionary for Regulatory Activities; N, number of patients in the analysis; PsA, psoriatic arthritis; PsO, psoriasis; PT, preferred term; SD, standard deviation; SEC, secukinumab.
Disclosure
I. McInnes: Other; I.M. has received research grants, consultation fees or speaker honoraria from AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. X. Baraliakos: Consultancies; X.B. is a consultant for AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen. Member of speakers’ bureau; X.B. is a member of the speakers' bureau for AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen. Grants/research support; X.B. has received grant/research support from AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen. A. Deodhar: Other; A.D. has received honoraria for consulting or speaking for, or has received research grants from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Eli Lilly, GlaxoSmithKline (GSK), Janssen, Novartis, Pfizer and UCB. A. Gottlieb: Other; A.G. has received research grants, consultation fees or speaker honoraria for lectures from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB. M. Lebwohl: Consultancies; M.L. is a consultant for Allergan, Almirall, Arcutis, Inc., Avotres Therapeutics, BirchBioMed Inc., Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Foundation for Research and Education in Dermatology, Inozyme Pharma, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Theravance and Verrica. Grants/research support; M.B. receives receives research funds from AbbVie, Amgen, Arcutis, AstraZeneca, Boehringer Ingelheim, Celgene, Clinuvel, Eli Lilly, Incyte, Janssen Research & Development, LLC, Kadmon Corp., LLC, LEO Pharma, Medimmune, Novartis, Ortho Dermatologics, Pfizer, Sciderm, UCB, Inc. and ViDac. S. Schreiber: Consultancies; S.S. has received consultation fees from AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, IMAB, Gilead, MSD, Mylan, Pfizer, Fresenius, Janssen, Takeda, Theravance, Provention Bio, Protagonist, and Dr Falk Pharma. K. Marfo: Other; K.M. is an employee of Novartis with Novartis stock. W. Bao: Other; W.B. is an employee of Novartis with Novartis stock. H. Richards: Other; H.B.R. is an employee of Novartis with Novartis stock. L. Pricop: Other; L.P. is an employee of Novartis with Novartis stock. A. Shete: Other; A.S. is an employee of Novartis with Novartis stock. J. Safi: Other; J.S. is an employee of Novartis with Novartis stock. P. Mease: Consultancies; P.M. is a consultant for AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB. Member of speakers’ bureau; P.M. is a member of the speakers' bureau for AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB. Grants/research support; P.M. has received grant/research support from AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB.
FRI0128 Integrated safety data analysis across phase 3 clinical studies for intravenous golimumab in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis