Malignancy Rates in Brodalumab Clinical Studies for Psoriasis

Alice Gottlieb, Mark Lebwohl, Clive Liu, Robert J Israel, Abby Jacobson, Alice Gottlieb, Mark Lebwohl, Clive Liu, Robert J Israel, Abby Jacobson

Abstract

Background: Brodalumab is a fully human anti-interleukin-17 receptor A monoclonal antibody efficacious for the treatment of adults with moderate-to-severe plaque psoriasis.

Objective: This study summarizes malignancy rates in psoriasis clinical studies of brodalumab.

Methods: Data were pooled from one phase II study and three large, multicenter, phase III randomized studies of brodalumab for the treatment of psoriasis, including two studies with randomization to brodalumab, ustekinumab, or placebo. Data from the 52-week (brodalumab and ustekinumab) and long-term (brodalumab) pools were summarized as exposure-adjusted or follow-up time-adjusted event rates per 100 patient-years (PY).

Results: Exposure-adjusted event rates per 100 PY at 52 weeks were lower with brodalumab (n = 4019; 3446 total PY of exposure) than with ustekinumab (n = 613; 495 total PY of exposure), including adjudicated malignancies (0.9 vs 2.6) and Surveillance, Epidemiology, and End Results (SEER)-adjudicated malignancies (0.3 vs 0.4). The exposure-adjusted event rate of adjudicated malignancies in the brodalumab group remained stable in the long-term analysis (0.9 [82 events]).

Conclusions: Rates of malignancy among brodalumab-treated patients with psoriasis were generally low.

Trial registry: ClinicalTrials.gov identifier NCT00975637; NCT01101100; NCT01708590 (AMAGINE-1); NCT01708603 (AMAGINE-2); NCT01708629 (AMAGINE-3).

Conflict of interest statement

Alice Gottlieb has served as a consultant or as an advisory board member for Janssen, Celgene, Bausch Health, Bristol-Myers Squibb, Beiersdorf, AbbVie, UCB, Novartis, Incyte, Eli Lilly, Dr. Reddy’s Laboratories, Dermira, Allergan, Sun Pharma, XBiotech, LEO Pharmaceuticals, Avotres Therapeutics, and Boehringer Ingelheim and has received research or educational grants from Janssen, Incyte, Novartis, XBiotech, UCB, and Boehringer Ingelheim. Mark Lebwohl is an employee of Mount Sinai, which receives research funds from AbbVie, Amgen, Arcutis, AstraZeneca, Boehringer Ingelheim, Celgene, Clinuvel, Eli Lilly, Incyte, Janssen Research & Development, LLC, Kadmon Corp., LLC, LEO Pharmaceuticals, Medimmune, Novartis, Ortho Dermatologics, Pfizer, Sciderm, UCB, Inc., and ViDac and has been 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 Pharmaceuticals, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Theravance, and Verrica. Clive Liu has served on speaker bureaus and participated in research and advisory boards for AbbVie, Celgene, Novartis, Lilly, Regeneron, Sanofi, Sun Pharma, Ortho Dermatologics, and Janssen. Robert J. Israel is an employee of Bausch Health US, LLC (an affiliate of Bausch Health Companies Inc.) and holds stock and/or stock options in the company. Abby Jacobson is an employee of Ortho Dermatologics (a division of Bausch Health US, LLC) and holds stocks and/or stock options in Bausch Health.

Figures

Fig. 1
Fig. 1
Malignancy event rates (52-week results). The all-brodalumab group includes all patients who received ≥ 1 dose of brodalumab. NMSC nonmelanoma skin cancer, PY total patient-years of exposure through week 52, Q2W every 2 weeks, SEER Surveillance, Epidemiology, and End Results

References

    1. Brauchli YB, Jick SS, Miret M, Meier CR. Psoriasis and risk of incident cancer: an inception cohort study with a nested case-control analysis. J Invest Dermatol. 2009;129(11):2604–2612. doi: 10.1038/jid.2009.113.
    1. Pouplard C, Brenaut E, Horreau C, Barnetche T, Misery L, Richard MA, et al. Risk of cancer in psoriasis: a systematic review and meta-analysis of epidemiological studies. J Eur Acad Dermatol Venereol. 2013;27(suppl 3):36–46. doi: 10.1111/jdv.12165.
    1. Kimball AB, Gladman D, Gelfand JM, Gordon K, Horn EJ, Korman NJ, et al. National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening. J Am Acad Dermatol. 2008;58(6):1031–1042. doi: 10.1016/j.jaad.2008.01.006.
    1. Paul CF, Ho VC, McGeown C, Christophers E, Schmidtmann B, Guillaume JC, et al. Risk of malignancies in psoriasis patients treated with cyclosporine: a 5 y cohort study. J Invest Dermatol. 2003;120(2):211–216. doi: 10.1046/j.1523-1747.2003.12040.x.
    1. Geller S, Xu H, Lebwohl M, Nardone B, Lacouture ME, Kheterpal M. Malignancy risk and recurrence with psoriasis and its treatments: a concise update. Am J Clin Dermatol. 2018;19(3):363–375. doi: 10.1007/s40257-017-0337-2.
    1. Kaushik SB, Lebwohl MG. Psoriasis: which therapy for which patient: psoriasis comorbidities and preferred systemic agents. J Am Acad Dermatol. 2019;80(1):27–40. doi: 10.1016/j.jaad.2018.06.057.
    1. Ngiow SF, Teng MW, Smyth MJ. A balance of interleukin-12 and -23 in cancer. Trends Immunol. 2013;34(11):548–555. doi: 10.1016/j.it.2013.07.004.
    1. Teng MW, Vesely MD, Duret H, McLaughlin N, Towne JE, Schreiber RD, et al. Opposing roles for IL-23 and IL-12 in maintaining occult cancer in an equilibrium state. Cancer Res. 2012;72(16):3987–3996. doi: 10.1158/0008-5472.CAN-12-1337.
    1. Siliq [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America, LLC; 2017.
    1. 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(14):1318–1328. doi: 10.1056/NEJMoa1503824.
    1. 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(2):273–286. doi: 10.1111/bjd.14493.
    1. 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. doi: 10.2147/DDDT.S113683.
    1. Tong Y, Peranteau AJ, Nawas Z, Tyring SK. A review of brodalumab, an IL-17 receptor antagonist, for moderate-to-severe plaque psoriasis. Skin Therapy Lett. 2017;22(1):1–6.
    1. Sbidian E, Chaimani A, Garcia-Doval I, Do G, Hua C, Mazaud C, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev. 2017;12:CD011535.
    1. 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(13):1181–1189. doi: 10.1056/NEJMoa1109017.
    1. 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(6):1183–90 e3.
    1. National Cancer Institute. Surveillance, Epidemiology, and End Results Program 2019. . Accessed 29 October 2019.
    1. Papp KA, Griffiths CE, Gordon K, Lebwohl M, Szapary PO, Wasfi Y, et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol. 2013;168(4):844–854. doi: 10.1111/bjd.12214.
    1. van de Kerkhof PC, Griffiths CE, Reich K, Leonardi CL, Blauvelt A, Tsai TF, et al. Secukinumab long-term safety experience: a pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2016;75(1):83–98 e4.
    1. Strober B, Leonardi C, Papp KA, Mrowietz U, Ohtsuki M, Bissonnette R, et al. Short- and long-term safety outcomes with ixekizumab from 7 clinical trials in psoriasis: etanercept comparisons and integrated data. J Am Acad Dermatol. 2017;76(3):432–40 e17.
    1. Mease P, Roussou E, Burmester GR, Goupille P, Gottlieb A, Moriarty SR, et al. Safety of ixekizumab in patients with psoriatic arthritis: results from a pooled analysis of three clinical trials. Arthritis Care Res (Hoboken). 2019;71(3):367–378. doi: 10.1002/acr.23738.
    1. Lebwohl M, Leonardi C, Wu JJ, et al. One-year pharmacovigilance update of brodalumab. Poster presented at: 20th Annual Las Vegas Dermatology Seminar; November 7–9, 2019; Las Vegas, NV.
    1. Blake SJ, Teng MW. Role of IL-17 and IL-22 in autoimmunity and cancer. Actas Dermosifiliogr. 2014;105(suppl 1):41–50. doi: 10.1016/S0001-7310(14)70017-1.
    1. Menter A, Thaci D, Wu JJ, Abramovits W, Kerdel F, Arikan D, et al. Long-term safety and effectiveness of adalimumab for moderate to severe psoriasis: results from 7-year interim analysis of the ESPRIT registry. Dermatol Ther (Heidelb). 2017;7(3):365–381. doi: 10.1007/s13555-017-0198-x.
    1. Kimball AB, Schenfeld J, Accortt NA, Anthony MS, Rothman KJ, Pariser D. Cohort study of malignancies and hospitalized infectious events in treated and untreated patients with psoriasis and a general population in the United States. Br J Dermatol. 2015;173(5):1183–1190. doi: 10.1111/bjd.14068.
    1. Strober B, Crowley J, Langley RG, Gordon K, Menter A, Leonardi C, et al. Systematic review of the real-world evidence of adalimumab safety in psoriasis registries. J Eur Acad Dermatol Venereol. 2018;32(12):2126–2133. doi: 10.1111/jdv.15203.
    1. Peleva E, Exton LS, Kelley K, Kleyn CE, Mason KJ, Smith CH. Risk of cancer in patients with psoriasis on biological therapies: a systematic review. Br J Dermatol. 2018;178(1):103–113. doi: 10.1111/bjd.15830.
    1. D’Haens G, Reinisch W, Colombel JF, Panes J, Ghosh S, Prantera C, et al. Five-year safety data from ENCORE, a European observational safety registry for adults with Crohn’s disease Treated with infliximab [Remicade(R)] or conventional therapy. J Crohns Colitis. 2017;11(6):680–689.
    1. D’Haens G, Reinisch W, Panaccione R, Satsangi J, Petersson J, Bereswill M, et al. Lymphoma risk and overall safety profile of adalimumab in patients with Crohn’s disease with up to 6 years of follow-up in the pyramid registry. Am J Gastroenterol. 2018;113(6):872–882. doi: 10.1038/s41395-018-0098-4.
    1. Hellgren K, Dreyer L, Arkema EV, Glintborg B, Jacobsson LT, Kristensen LE, et al. Cancer risk in patients with spondyloarthritis treated with TNF inhibitors: a collaborative study from the ARTIS and DANBIO registers. Ann Rheum Dis. 2017;76(1):105–111. doi: 10.1136/annrheumdis-2016-209270.
    1. Mercer LK, Galloway JB, Lunt M, Davies R, Low AL, Dixon WG, et al. Risk of lymphoma in patients exposed to antitumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Ann Rheum Dis. 2017;76(3):497–503. doi: 10.1136/annrheumdis-2016-209389.
    1. Chakravarty EF, Michaud K, Wolfe F. Skin cancer, rheumatoid arthritis, and tumor necrosis factor inhibitors. J Rheumatol. 2005;32(11):2130–2135.
    1. Chen Y, Friedman M, Liu G, Deodhar A, Chu CQ. Do tumor necrosis factor inhibitors increase cancer risk in patients with chronic immune-mediated inflammatory disorders? Cytokine. 2018;101:78–88. doi: 10.1016/j.cyto.2016.09.013.
    1. Raaschou P, Simard JF, Holmqvist M, Askling J, Group AS. Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population based prospective cohort study from Sweden. BMJ. 2013;346:f1939.
    1. Nardone B, Hammel JA, Raisch DW, Weaver LL, Schneider D, West DP. Melanoma associated with tumour necrosis factor-alpha inhibitors: a Research on Adverse Drug events And Reports (RADAR) project. Br J Dermatol. 2014;170(5):1170–1172. doi: 10.1111/bjd.12779.
    1. Chen Y, Sun J, Yang Y, Huang Y, Liu G. Malignancy risk of anti-tumor necrosis factor alpha blockers: an overview of systematic reviews and meta-analyses. Clin Rheumatol. 2016;35(1):1–18. doi: 10.1007/s10067-015-3115-7.
    1. Fiorentino D, Ho V, Lebwohl MG, Leite L, Hopkins L, Galindo C, et al. Risk of malignancy with systemic psoriasis treatment in the Psoriasis Longitudinal Assessment Registry. J Am Acad Dermatol. 2017;77(5):845–854. doi: 10.1016/j.jaad.2017.07.013.
    1. Gottlieb AB, Kalb RE, Langley RG, Krueger GG, de Jong EM, Guenther L, et al. Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): experience with infliximab and other systemic and biologic therapies. J Drugs Dermatol. 2014;13(12):1441–1448.
    1. Papp K, Gottlieb AB, Naldi L, Pariser D, Ho V, Goyal K, et al. Safety surveillance for ustekinumab and other psoriasis treatments from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) J Drugs Dermatol. 2015;14(7):706–714.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅