Safety of Brodalumab in Plaque Psoriasis: Integrated Pooled Data from Five Clinical Trials
Keywords:brodalumab, interleukin-17, psoriasis, safety
Brodalumab is approved for treatment of moderate-to-severe plaque psoriasis. Here, we assess the safety profile of brodalumab using pooled safety data from 5 phase II/III trials of brodalumab 140 mg or 210 mg. In total, 4,464 patients received brodalumab, representing 8,891.6 patient-years of exposure. During the placebo-controlled 12-week induction period, rates of serious adverse events per 100 patient-years were 10.8 and 9.6 (brodalumab 140 mg and 210 mg, respectively) vs 4.3 and 6.5 (ustekinumab and placebo, respectively); infections were the most frequent serious adverse event. Rates of serious adverse events during the comparator-controlled 52-week period were 14.4, 10.2 and 8.3 per 100 patient-years for brodalumab 210 mg, brodalumab 140 mg, and ustekinumab, respectively. Brodalumab was not associated with increased risks of malignancy, major adverse cardiac events, suicidal ideation and behaviour, or fatal events. Overall, brodalumab demonstrated an acceptable safety profile in short- and long-term treatment.
Egeberg A, Mallbris L, Warren RB, Bachelez H, Gislason GH, Hansen PR, et al. Association between psoriasis and inflammatory bowel disease: a Danish nationwide cohort study. Br J Dermatol 2016; 175: 487-492.
https://doi.org/10.1111/bjd.14528 DOI: https://doi.org/10.1111/bjd.14528
Lonnberg AS, Skov L. Co-morbidity in psoriasis: mechanisms and implications for treatment. Expert Rev Clin Immunol 2017; 13: 27-34.
https://doi.org/10.1080/1744666X.2016.1213631 DOI: https://doi.org/10.1080/1744666X.2016.1213631
Takeshita J, Grewal S, Langan SM, Mehta NN, Ogdie A, Van Voorhees AS, et al. Psoriasis and comorbid diseases: epidemiology. J Am Acad Dermatol 2017; 76: 377-390.
https://doi.org/10.1016/j.jaad.2016.07.064 DOI: https://doi.org/10.1016/j.jaad.2016.07.064
Strober B, Ryan C, van de Kerkhof P, van der Walt J, Kimball AB, Barker J, et al. Recategorization of psoriasis severity: Delphi consensus from the International Psoriasis Council. J Am Acad Dermatol 2020; 82: 117-122.
https://doi.org/10.1016/j.jaad.2019.08.026 DOI: https://doi.org/10.1016/j.jaad.2019.08.026
Sawyer LM, Cornic L, Levin LÅ, Gibbons C, Møller AH, Jemec GB. Long-term efficacy of novel therapies in moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis of PASI response. J Eur Acad Dermatol Venereol 2019; 33: 355-366.
https://doi.org/10.1111/jdv.15277 DOI: https://doi.org/10.1111/jdv.15277
Sawyer LM, Malottki K, Sabry-Grant C, Yasmeen N, Wright E, Sohrt A, et al. Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis of PASI response. PLoS One 2019; 14: e0220868-e0220868.
https://doi.org/10.1371/journal.pone.0220868 DOI: https://doi.org/10.1371/journal.pone.0220868
Loos AM, Liu S, Segel C, Ollendorf DA, Pearson SD, Linder JA. Comparative effectiveness of targeted immunomodulators for the treatment of moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis. J Am Acad Dermatol 2018; 79: 135-144.e7.
https://doi.org/10.1016/j.jaad.2018.02.027 DOI: https://doi.org/10.1016/j.jaad.2018.02.027
Russell CB, Rand H, Bigler J, Kerkof K, Timour M, Bautista E, et al. Gene expression profiles normalized in psoriatic skin by treatment with brodalumab, a human anti-IL-17 receptor monoclonal antibody. J Immunol 2014; 192: 3828-3836.
https://doi.org/10.4049/jimmunol.1301737 DOI: https://doi.org/10.4049/jimmunol.1301737
Frieder J, Kivelevitch D, Menter A. Secukinumab: a review of the anti-IL-17A biologic for the treatment of psoriasis. Ther Adv Chronic Dis 2018; 9: 5-21.
https://doi.org/10.1177/2040622317738910 DOI: https://doi.org/10.1177/2040622317738910
Hawkes JE, Chan TC, Krueger JG. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol 2017; 140: 645-653.
https://doi.org/10.1016/j.jaci.2017.07.004 DOI: https://doi.org/10.1016/j.jaci.2017.07.004
Papp KA, Reich K, Paul C, Blauvelt A, Baran W, Bolduc C, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol 2016; 175: 273-286.
https://doi.org/10.1111/bjd.14493 DOI: https://doi.org/10.1111/bjd.14493
Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med 2015; 373: 1318-1328.
https://doi.org/10.1056/NEJMoa1503824 DOI: https://doi.org/10.1056/NEJMoa1503824
Lebwohl MG, Blauvelt A, Menter A, Papp KA, Guenthner S, Pillai R, et al. Efficacy, safety, and patient-reported outcomes in patients with moderate-to-severe plaque psoriasis treated with brodalumab for 5 years in a long-term, open-label, Phase II study. Am J Clin Dermatol 2019; 20: 863-871.
https://doi.org/10.1007/s40257-019-00466-2 DOI: https://doi.org/10.1007/s40257-019-00466-2
Papp K, Leonardi C, Menter A, Thompson EH, Milmont CE, Kricorian G, et al. Safety and efficacy of brodalumab for psoriasis after 120 weeks of treatment. J Am Acad Dermatol 2014; 71: 1183-1190.e3.
https://doi.org/10.1016/j.jaad.2014.08.039 DOI: https://doi.org/10.1016/j.jaad.2014.08.039
Langley RG, Armstrong AW, Lebwohl MG, Blauvelt A, Hsu S, Tyring S, et al. Efficacy and safety of brodalumab in patients with psoriasis who had inadequate responses to ustekinumab: subgroup analysis of two randomized phase III trials. Br J Dermatol 2019; 180: 306-314.
https://doi.org/10.1111/bjd.17318 DOI: https://doi.org/10.1111/bjd.17318
Puig L, Lebwohl M, Bachelez H, Sobell J, Jacobson AA. Long-term efficacy and safety of brodalumab in the treatment of psoriasis: 120-week results from the randomized, double-blind, placebo- and active comparator-controlled phase 3 AMAGINE-2 trial. J Am Acad Dermatol 2020; 82: 352-359.
https://doi.org/10.1016/j.jaad.2019.05.095 DOI: https://doi.org/10.1016/j.jaad.2019.05.095
Blair HA. Brodalumab: a review in moderate to severe plaque psoriasis. Drugs 2018; 78: 495-504.
https://doi.org/10.1007/s40265-018-0888-4 DOI: https://doi.org/10.1007/s40265-018-0888-4
Lebwohl MG, Papp KA, Marangell LB, Koo J, Blauvelt A, Gooderham M, et al. Psychiatric adverse events during treatment with brodalumab: analysis of psoriasis clinical trials. J Am Acad Dermatol 2018; 78: 81-89.e5.
https://doi.org/10.1016/j.jaad.2017.08.024 DOI: https://doi.org/10.1016/j.jaad.2017.08.024
Puig L. Brodalumab: the first anti-IL-17 receptor agent for psoriasis. Drugs Today (Barc) 2017; 53: 283-297.
https://doi.org/10.1358/dot.2017.53.5.2613690 DOI: https://doi.org/10.1358/dot.2017.53.5.2613690
Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG, Kricorian G, et al. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med 2012; 366: 1181-1189.
https://doi.org/10.1056/NEJMoa1109017 DOI: https://doi.org/10.1056/NEJMoa1109017
Gupta SK. Intention-to-treat concept: a review. Perspect Clin Res 2011; 2: 109-112.
https://doi.org/10.4103/2229-3485.83221 DOI: https://doi.org/10.4103/2229-3485.83221
Armstrong A, Paul C, Puig L, Boehncke WH, Freeman M, Torii H, et al. Safety of ixekizumab treatment for up to 5 years in adult patients with moderate-to-severe psoriasis: results from greater than 17,000 patient-years of exposure. Dermatol Ther (Heidelb) 2020; 10: 133-150.
https://doi.org/10.1007/s13555-019-00340-3 DOI: https://doi.org/10.1007/s13555-019-00340-3
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.
https://doi.org/10.1186/s13075-019-1882-2 DOI: https://doi.org/10.1186/s13075-019-1882-2
Ali Z, Matthews R, Al-Janabi A, Warren RB. Bimekizumab: a dual IL-17A and IL-17F inhibitor for the treatment of psoriasis and psoriatic arthritis. Expert Rev Clin Immunol 2021; 17: 1073-1081.
https://doi.org/10.1080/1744666X.2021.1967748 DOI: https://doi.org/10.1080/1744666X.2021.1967748
Silfvast-Kaiser A, Paek SY, Menter A. Anti-IL17 therapies for psoriasis. Expert Opin Biol Ther 2019; 19: 45-54.
https://doi.org/10.1080/14712598.2019.1555235 DOI: https://doi.org/10.1080/14712598.2019.1555235
Roman M, Chiu MW. Spotlight on brodalumab in the treatment of moderate-to-severe plaque psoriasis: design, development, and potential place in therapy. Drug Des Devel Ther 2017; 11: 2065-2075.
https://doi.org/10.2147/DDDT.S113683 DOI: https://doi.org/10.2147/DDDT.S113683
Kynetheum. Industriparken 55 DK-2750 Ballerup Denmark: LEO Pharma A/S, 2017.
Hu SC, Lan CE. Psoriasis and cardiovascular comorbidities: focusing on severe vascular events, cardiovascular risk factors and implications for treatment. Int J Mol Sci 2017; 18: 2211.
https://doi.org/10.3390/ijms18102211 DOI: https://doi.org/10.3390/ijms18102211
How to Cite
Copyright (c) 2022 Kristian Reich, Diamant Thaçi, Georg Stingl, Jens Strodl Andersen, Line Conradsen Hiort, Michala Oron Lexner, David Winkler, Carle Paul
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All digitalized ActaDV contents is available freely online. The Society for Publication of Acta Dermato-Venereologica owns the copyright for all material published until volume 88 (2008) and as from volume 89 (2009) the journal has been published fully Open Access, meaning the authors retain copyright to their work.
Unless otherwise specified, all Open Access articles are published under CC-BY-NC licences, 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.