fetching data ...

FRI0272 (2020)
SECUKINUMAB DEMONSTRATES A CONSISTENT SAFETY PROFILE IN PATIENTS WITH PSORIASIS, PSORIATIC ARTHRITIS AND ANKYLOSING SPONDYLITIS OVER LONG TERM: UPDATED POOLED SAFETY ANALYSES
A. Deodhar1, I. Mcinnes2, X. Baraliakos3, K. Reich4,5, A. B. Gottlieb6, M. Lebwohl7, S. Schreiber8, W. Bao9, K. Marfo10, H. Richards10, L. Pricop9, A. Shete10, J. Safi9, P. J. Mease11
1Oregon Health & Science University, Portland, United States of America
2University of Glasgow, Glasgow, United Kingdom
3Ruhr-University Bochum, Bochum, Germany
4University Medical Center Hamburg-Eppendorf, Hamburg, Germany
5Skinflammation® Center, Hamburg, Germany
6Icahn School of Medicine at Mount Sinai, New York, United States of America
7Mount Sinai Hospital, New York, United States of America
8University Hospital Schleswig-Holstein, Kiel, Germany
9Novartis Pharmaceuticals Corp., East Hanover, United States of America
10Novartis Pharma AG, Basel, Switzerland
11Swedish Medical Center and University of Washington, Seattle, United States of America

Background: Pooled safety data has been reported with secukinumab (SEC) in patients (pts) with Psoriatic arthritis (PsA), Ankylosing Spondylitis (AS) and Psoriasis (PsO). 1


Objectives: To report longer-term safety data of SEC treatment in PsA, AS, PsO pts up to 5 years.


Methods: The integrated clinical trial safety dataset included data pooled from 28 randomised controlled clinical trials of SEC 300 or 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 with a cut-off date of 25 December 2018. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 pt-years. Analyses included all pts who received ≥1 dose of SEC.


Results: A total of 12637 pts (8819, 2678 and 1140 pts with PsO, PsA and AS, with an exposure of 15063.1, 5984.6 and 3527.2 pt-years, respectively) were included. The most frequent AE was upper respiratory tract infection and EAIR per 100 pt-years for IBD, malignancies and MACE remained low. The EAIR per 100 pt-years for adverse events (AEs) of special interest are reported in Table 1 . The cumulative post-marketing exposure to SEC was estimated to be ~285,811 pt-years across the approved indications. Safety data from post-marketing surveillance are reported in Table 2 .

Selected AEs of interest with SEC across pooled clinical trials

Variable PsO PsA AS
SEC N=8819 SEC N=2678 SEC N=1140
Exposure (Days), Mean (SD) 623.9 (567.7) 816.2 (580.7) 1130.1 (583.0)
Death, n (%) 15 (0.2) 13 (0.5) 10 (0.9)
Selected AE’s of interest, EAIR (95% CI)
Serious infections 1 1.4 (1.2, 1.6) 1.8 (1.5, 2.2) 1.2 (0.9, 1.6)
Candida infections 2 2.9 (2.7, 3.2) 1.5 (1.2, 1.9) 0.7 (0.5, 1.1)
IBD 3 Crohn’s disease 3 Ulcerative colitis 3 0.01 (0.0, 0.05) 0.1 (0.05, 0.2) 0.1 (0.08, 0.2) 0.03 (0.0, 0.1) 0.1 (0.04, 0.2) 0.1 (0.04, 0.2) 0.03 (0.0, 0.2) 0.4 (0.24, 0.7) 0.2 (0.1, 0.5)
MACE 4 0.4 (0.31, 0.5) 0.4 (0.3, 0.6) 0.7 (0.4, 1.0)
Uveitis 3 0.01 (0.0, 0.05) 0.1 (0.04, 0.2) 1.2 (0.9, 1.7)
Malignancy 5 0.9 (0.7, 1.0) 1.0 (0.77, 1.3) 0.5 (0.3, 0.8)

1 Rates for system organ class; 2 Rates for high level term; 3 Rates for preferred term (PT; IBD for unspecified IBD); 4 Rates for Novartis MedDRA Query term; 5 Rates for standardized MedDRA query term – ‘malignancies and unspecified tumour’; EAIR, exposure adjusted incidence rate per 100 pt-years; N, number of pts in the analysis

Summary of SEC post-marketing safety

Exposure (PTY) PSUR1 26Dec14 -25Jun15 PSUR2 26 Jun - 25Dec15 PSUR3 26Dec15 -25Jun16 PSUR4 26Jun -25Dec16 PSUR5 26Dec16 -25Dec17 PSUR6 26Dec17 -25Dec18 Cumulative
1838 7450 16871 28549 93744 137325 285811
                    n (Reporting rate PTY)
Serious infections 89 (4.8) 149 (2.0) 232 (1.4) 475 (1.7) 649 (0.7) 1841 (1.3) 3980 (1.4)
Malignancy 2 (0.1) 15 (0.2) 21 (0.1) 50 (0.2) 225 (0.2) 422 (0.3) 788 (0.3)
Total IBD 4 (0.2) 12 (0.2) 37(0.2) 46 (0.2) 185 (0.2) 340 (0.3) 693 (0.2)
MACE 6 (0.3) 15 (0.2) 16 (0.1) 39 (0.1) 151 (0.2) 238 (0.2) 504 (0.2)

PSUR, periodic safety update report; PTY, pt-treatment years


Conclusion: In this long-term analysis across clinical trials and post-marketing surveillance, of pts with PsO, PsA and AS, SEC was well tolerated, with a safety profile consistent with previous reports. 1


REFERENCE:

[1]Deodhar et al. Arthritis Research & Therapy (2019) 21:111.


Disclosure of Interests: Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Kristian Reich Grant/research support from: Affibody; Almirall; Amgen; Biogen; Boehringer Ingelheim; Celgene; Centocor; Covagen; Eli Lilly; Forward Pharma; Fresenius Medical Care; GlaxoSmithKline; Janssen; Kyowa Kirin; LEO Pharma; Medac; Merck; Novartis; Miltenyi Biotec; Ocean Pharma; Pfizer; Regeneron; Samsung Bioepis; Sanofi Genzyme; Takeda; UCB; Valeant and Xenoport., Consultant of: Affibody; Almirall; Amgen; Biogen; Boehringer Ingelheim; Celgene; Centocor; Covagen; Eli Lilly; Forward Pharma; Fresenius Medical Care; GlaxoSmithKline; Janssen; Kyowa Kirin; LEO Pharma; Medac; Merck; Novartis; Miltenyi Biotec; Ocean Pharma; Pfizer; Regeneron; Samsung Bioepis; Sanofi Genzyme; Takeda; UCB; Valeant and Xenoport., Speakers bureau: Affibody; Almirall; Amgen; Biogen; Boehringer Ingelheim; Celgene; Centocor; Covagen; Eli Lilly; Forward Pharma; Fresenius Medical Care; GlaxoSmithKline; Janssen; Kyowa Kirin; LEO Pharma; Medac; Merck; Novartis; Miltenyi Biotec; Ocean Pharma; Pfizer; Regeneron; Samsung Bioepis; Sanofi Genzyme; Takeda; UCB; Valeant and Xenoport., Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Mark Lebwohl Grant/research support from: AbbVie, Amgen, Arcutis, AstraZeneca, Boehringer Ingelheim, Celgene, Clinuvel, Eli Lilly, Incyte, Janssen Research & Development, LLC, Kadmon Corp., LLC, Leo Pharmaceutucals, Medimmune, Novartis, Ortho Dermatologics, Pfizer, Sciderm, UCB, Inc., and ViDac, Consultant of: 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, Stefan Schreiber Consultant of: AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, IMAB, Gilead, MSD, Mylan, Pfizer, Fresenius, Janssen, Takeda, Theravance, provention Bio, Protagonist and Falk, Weibin Bao Shareholder of: Novartis, Employee of: Novartis, Kwaku Marfo Shareholder of: Novartis, Employee of: Novartis, Hanno Richards Shareholder of: Novartis, Employee of: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Abhijit Shete Shareholder of: Novartis, Employee of: Novartis, Jorge Safi Shareholder of: Novartis, Employee of: Novartis, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Citation: Ann Rheum Dis, volume 79, supplement 1, year 2020, page 718
Session: Spondyloarthritis - treatment (Poster Presentations)