Long-term Safety of Secukinumab Over Five Years in Patients with Moderate-to-severe Plaque Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis: Update on Integrated Pooled Clinical Trial and Post-marketing Surveillance Data
Keywords:Ankylosing spondylitis, biologics, interleukin, psoriasis, psoriatic arthritis, safety
Secukinumab, a selective interleukin (IL)-17A inhibitor, is approved for use in adult and paediatric psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis. The aim of this study was to report the long-term safety of secukinumab in pooled data from 28 clinical trials and a post-marketing safety surveillance in psoriasis, psoriatic arthritis and ankylosing spondylitis patients. Analyses included 12,637 secukinumab-treated patients, corresponding to 15,063, 5,985 and 3,527 patient-years of exposure in psoriasis, psoriatic arthritis and ankylosing spondylitis patients, respectively. Incidences of serious adverse events were low, with no identifiable patterns across indications. Active tuberculosis or latent tuberculosis infections were rare. The incidence of opportunistic infections was < 0.2/100 patient-years, the incidence of malignancy was ≤ 1/100 patient-years, and the incidence of major adverse cardiovascular events was < 0.7/100 patient-years, with no apparent increases over time. Secukinumab demonstrated a favourable safety profile for up to 5 years of treatment across the 3 indications, and no new safety signals were identified.
Beringer A, Noack M, Miossec P. IL-17 in chronic inflammation: from discovery to targeting. Trends Mol Med 2016; 22: 230-241.
Blauvelt A, Chiricozzi A. The immunologic role of IL-17 in psoriasis and psoriatic arthritis pathogenesis. Clin Rev Allergy Immunol 2018; 55: 379-390.
Patel DD, Lee DM, Kolbinger F, Antoni C. Effect of IL-17A blockade with secukinumab in autoimmune diseases. Ann Rheum Dis 2013; 72: ii116-ii123.
McGeachy MJ, Cua DJ, Gaffen SL. The IL-17 family of cytokines in health and disease. Immunity 2019; 50: 892-906.
Elmets CA, Leonardi CL, Davis DMR, Gelfand JM, Lichten J, Mehta NN, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol 2019; 80: 1073-1113.
Liew JW, Ramiro S, Gensler LS. Cardiovascular morbidity and mortality in ankylosing spondylitis and psoriatic arthritis. Best Pract Res Clin Rheumatol 2018; 32: 369-389.
Molto A, Dougados M. Comorbidities in spondyloarthritis including psoriatic arthritis. Best Pract Res Clin Rheumatol 2018; 32: 390-400.
Ogdie A, Yu Y, Haynes K, Love TJ, Maliha S, Jiang Y, et al. Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study. Ann Rheum Dis 2015; 74: 326-332.
Perez-Chada LM, Merola JF. Comorbidities associated with psoriatic arthritis: review and update. Clin Immunol 2020; 214: 108397.
Puig L. Cardiometabolic comorbidities in psoriasis and psoriatic arthritis. Int J Mol Sci 2017; 19: 58.
Zhao SS, Ermann J, Xu C, Lyu H, Tedeschi SK, Liao KP, et al. Comparison of comorbidities and treatment between ankylosing spondylitis and non-radiographic axial spondyloarthritis in the United States. Rheumatology (Oxford) 2019; 58: 2025-2030.
Ananthakrishnan AN, Bernstein CN, Iliopoulos D, Macpherson A, Neurath MF, Ali RAR, et al. Environmental triggers in IBD: a review of progress and evidence. Nat Rev Gastroenterol Hepatol 2018; 15: 39-49.
Schreiber S, Colombel JF, Feagan BG, Reich K, Deodhar AA, McInnes IB, et al. Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials. Ann Rheum Dis 2019; 78: 473-479.
Armstrong AW, Vender R, Kircik L. Secukinumab in the treatment of palmoplantar, nail, scalp, and pustular psoriasis. J Clin Aesthet Dermatol 2016; 9: S12-S16.
Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, et al. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med 2015; 373: 2534-2548.
Blauvelt A, Prinz JC, Gottlieb AB, Kingo K, Sofen H, Ruer-Mulard M, et al. Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol 2015; 172: 484-493.
Deodhar A, Mease PJ, McInnes IB, Baraliakos X, Reich K, Blauvelt A, et al. Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post-marketing surveillance data. Arthritis Res Ther 2019; 21: 111.
Gottlieb AB, Blauvelt A, Prinz JC, Papanastasiou P, Pathan R, Nyirady J, et al. Secukinumab self-administration by prefilled syringe maintains reduction of plaque psoriasis severity over 52 weeks: results of the FEATURE trial. J Drugs Dermatol 2016; 15: 1226-1234.
Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, et al. Secukinumab in plaque psoriasis - results of two phase 3 trials. N Engl J Med 2014; 371: 326-338.
Paul C, Lacour JP, Tedremets L, Kreutzer K, Jazayeri S, Adams S, et al. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol 2015; 29: 1082-1090.
Reich K, Warren RB, Coates LC, Di Comite G. Long-term efficacy and safety of secukinumab in the treatment of the multiple manifestations of psoriatic disease. J Eur Acad Dermatol Venereol 2020; 34: 1161-1173.
Data on file. COSENTYX Access. Novartis Pharmaceuticals Corp; June 2021.
Blauvelt A, Reich K, Tsai TF, Tyring S, Vanaclocha F, Kingo K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: Results from the CLEAR study. J Am Acad Dermatol 2017; 76: 60-69.e9.
McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2015; 386: 1137-1146.
Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med 2015; 373: 1329-1339.
Mrowietz U, Leonardi CL, Girolomoni G, Toth D, Morita A, Balki SA, et al. Secukinumab retreatment-as-needed versus fixed-interval maintenance regimen for moderate to severe plaque psoriasis: a randomized, double-blind, noninferiority trial (SCULPTURE). J Am Acad Dermatol 2015; 73: 27-36.e21.
Thaci D, Blauvelt A, Reich K, Tsai TF, Vanaclocha F, Kingo K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol 2015; 73: 400-409.
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013; 310: 2191-2194.
Stolwijk C, van Tubergen A, Castillo-Ortiz JD, Boonen A. Prevalence of extra-articular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis. Ann Rheum Dis 2015; 74: 65-73.
Strober BE, Langley RGB, Menter A, Magid M, Porter B, Fox T, et al. No elevated risk for depression, anxiety or suicidality with secukinumab in a pooled analysis of data from 10 clinical studies in moderate-to-severe plaque psoriasis. Br J Dermatol 2018; 178: e105-e107.
Vallabhaneni S, Chiller TM. Fungal infections and new biologic therapies. Curr Rheumatol Rep 2016; 18: 29.
Wakkee M, de Vries E, van den Haak P, Nijsten T. Increased risk of infectious disease requiring hospitalization among patients with psoriasis: a population-based cohort. J Am Acad Dermatol 2011; 65: 1135-1144.
Schett G, Sticherling M, Neurath MF. COVID-19: risk for cytokine targeting in chronic inflammatory diseases? Nat Rev Immunol 2020; 20: 271-272.
Felder JB, Korelitz BI, Rajapakse R, Schwarz S, Horatagis AP, Gleim G. Effects of nonsteroidal antiinflammatory drugs on inflammatory bowel disease: a case-control study. Am J Gastroenterol 2000; 95: 1949-1954.
Molodecky NA, Kaplan GG. Environmental risk factors for inflammatory bowel disease. Gastroenterol Hepatol (NY) 2010; 6: 339-346.
Timmer A. Environmental influences on inflammatory bowel disease manifestations. Lessons from epidemiology. Dig Dis 2003; 21: 91-104.
Molnar T, Lakatos PL, Farkas K, Nagy F, Szepes Z, Miheller P, et al. Predictors of relapse in patients with Crohn's disease in remission after 1 year of biological therapy. Aliment Pharmacol Ther 2013; 37: 225-233.
Kennedy NA, Warner B, Johnston EL, Flanders L, Hendy P, Ding NS, et al. Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis. Aliment Pharmacol Ther 2016; 43: 910-923.
Gouveia EB, Elmann D, Morales MS. Ankylosing spondylitis and uveitis: overview. Rev Bras Reumatol 2012; 52: 742-756.
Lebwohl M, Deodhar A, Griffiths CEM, Menter MA, Poddubnyy D, Bao W, et al. The risk of malignancy in patients with secukinumab-treated psoriasis, psoriatic arthritis and ankylosing spondylitis: analysis of clinical trial and postmarketing surveillance data with up to five years of follow-up. Br J Dermatol 2021; 185: 935-944.
How to Cite
Copyright (c) 2022 Alice B. Gottlieb, Atul Deodhar, Iain B. Mcinnes, Xenofon Baraliakos, Kristian Reich, Stefan Schreiber, Weibin Bao, Kwaku Marfo, Hanno B. Richards, Luminita Pricop, Abhijit Shete, Vivek Trivedi, Deborah Keefe, Charis C. Papavassilis, Piotr Jagiello, Philemon Papanastasiou, Philip J. Mease, Mark Lebwohl
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.