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. 2025 Jul 9;161(10):1048-1056.
doi: 10.1001/jamadermatol.2025.2056. Online ahead of print.

Ixekizumab and Malignant Neoplasms: A Pooled Analysis of Data From 25 Randomized Clinical Trials

Joseph F Merola  1 , Kim A Papp  2   3 , Atul Deodhar  4 , Andrew Blauvelt  5 , Andris Kronbergs  6 , Meghan Feely McDonald  7 , Nadezdha Eberhart  6 , Danting Zhu  6 , Elsa Inman  6 , Elsie Grace  6 , Thorsten Holzkaemper  6 , Proton Rahman  8 , Helena Marzo-Ortega  9 , Alice B Gottlieb  10 , Sergio Schwartzman  11 , Mark Lebwohl  7
Affiliations

Ixekizumab and Malignant Neoplasms: A Pooled Analysis of Data From 25 Randomized Clinical Trials

Joseph F Merola et al. JAMA Dermatol. .

Abstract

Importance: Assessing malignant neoplasm risk among patients with long-term biologic exposure is of interest. This study provides insight into the risk of malignant neoplasm among patients with psoriasis (PsO), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) who received ixekizumab (IXE) over time.

Objective: To determine the incidence of malignant neoplasms among patients with PsO, PsA, or axSpA who received long-term (up to 6 years) IXE treatment, and to compare the recorded incidences (excluding nonmelanoma skin cancer) with those observed in the US general population.

Design, setting, and participants: This multicenter, global pooled analysis examined patient data from 25 randomized clinical trials (RCTs) in patients with PsO, PsA, or axSpA receiving at least 1 dose of IXE over 5 years (PsO) or 3 years (PsA and axSpA). Eligibility criteria varied across the 25 RCTs, but most of the patients were naive to biologic treatments. The primary analysis was performed in March 2021 (PsA) and March 2022 (PsO and axSpA).

Intervention: Long-term treatment with IXE.

Main outcomes and measures: Incidence rates of malignant neoplasms and standardized incidence ratios (SIRs).

Results: The mean age across the 3 indications was 45.9 years; most patients in the PsO and axSpA cohorts were male (4696/6892 [68.1%] and 650/932 [69.7%], respectively), whereas the proportion of male to female patients in the PsA cohort was largely balanced (679/1401 [48.5%] vs 722/1401 [51.5%], respectively). The study included 6892 patients with PsO, 1401 patients with PsA, and 932 patients with axSpA, representing a cumulative exposure to IXE of 22 371.1 patient-years (PY) (18 025.7 PY for PsO, 2247.7 PY for PsA, and 2097.7 PY for axSpA). Malignant neoplasms were reported among 141 patients with PsO (2.0%; incidence rate [IR], 0.8 per 100 PY [95% CI, 0.7-0.9]), 15 patients with PsA (1.1%; IR, 0.7 per 100 PY [95% CI, 0.4-1.1]), and 9 patients with axSpA (1.0%; IR, 0.4 per 100 PY [95% CI, 0.2-0.8]). IRs of malignant neoplasms at 1-year intervals remained low (≤1.2 per 100 PY) and constant over time. SIRs with 95% CIs were below or near 1 (PsO, 0.89 [95% CI, 0.71-1.08]; PsA, 0.49 [95% CI, 0.13-0.85]; axSpA, 1.07 [95% CI, 0.37-1.77]).

Conclusions and relevance: This pooled analysis of 25 RCTs demonstrated that the safety profile of IXE supports long-term use in patients with PsO, PsA, or axSpA. This is evidenced by incidences of malignant neoplasms consistent with previous reports, and with SIRs of malignant neoplasms across indications similar to the US general population.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Merola reported being a consultant and/or investigator for Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly and Company, MoonLake, Novartis, Janssen, Oruka, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, and Pfizer. Dr Papp reported receiving personal fees from AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bain Capital, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite BioPharma, Celltrion, Concert Pharmaceuticals, CorEvitas, Dermavant, Dermira, Dice Therapeutics, Eli Lilly and Company, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte, Janssen, Kenvue, Kymab, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Mitsubishi Pharma, Nektar, Nimbus Therapeutics, Novartis, Pfizer, Reistone, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB, and Zai Lab outside the submitted work. Dr Deodhar reported receiving grants and honorarium from Eli Lilly and Company during the conduct of the study; writing support from AbbVie; and grants and honoraria from Bristol Myers Squibb, Johnson & Johnson, MoonLake, Pfizer, Novartis, and UCB outside the submitted work. Dr Blauvelt reported serving as a speaker for and receiving honoraria from Eli Lilly and Company and UCB; serving as a scientific advisor for and receiving honoraria from AbbVie, Almirall, Alumis, Amgen, AnaptysBio, Apogee, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Corvus, Dermavant, Eli Lilly and Company, Galderma, GlaxoSmithKline, Incyte, IQVIA, Janssen, LEO Pharma, Lipidio, Merck, Novartis, Oruka, Paragon, Pfizer, Regeneron, Sanofi, Spherix Global Insights, Sun Pharma, Takeda, UCB, and Union; acting as a clinical study investigator for AbbVie, Acelyrin, Almirall, Alumis, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Galderma, Incyte, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, Takeda, and UCB; and owning stock in Lipidio and Oruka. Dr Feely McDonald reported being a shareholder and former employee of Eli Lilly and Company outside the submitted work. Dr Zhu reported being a shareholder in Eli Lilly and Company. Dr Inman reported being a shareholder in Eli Lilly and Company outside the submitted work. Dr Grace reported being a shareholder in Eli Lilly and Company. Dr Holzkaemper reported being a shareholder in Eli Lilly and Company. Dr Rahman reported receiving consulting fees from Janssen, Eli Lilly and Company, Novartis, UCB, and AbbVie outside the submitted work. Dr Marzo-Ortega reported receiving grants from Janssen, Novartis, Pfizer, and UCB during the conduct of the study; personal fees from AbbVie, Amgen, Biogen, Eli Lilly and Company, Janssen, MoonLake, Novartis, Pfizer, Takeda, and UCB; and being supported by the National Institute for Health and Care Research Leeds Biomedical Research Centre outside the submitted work. Dr Gottlieb reported receiving nonfinancial support from Eli Lilly and Company during the conduct of the study; personal fees from UCB, Janssen, Takeda, Bristol Myers Squibb, and Novartis; grants from UCB, Janssen, and Bristol Myers Squibb; and nonfinancial support from MoonLake, Takeda, Novartis, and Boehringer Ingelheim outside the submitted work. Dr Lebwohl reported receiving research funds from AbbVie, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Clexio, Dermavant, Eli Lilly, Incyte, Inozyme, Johnson & Johnson, Pfizer, Sanofi-Regeneron, UCB, and Facilitation of International Dermatology Education; and serving as a consultant for Aikium, Almirall, AltruBio, Amgen, Apogee, Arcutis, AstraZeneca, Atomwise, Avotres, Boehringer Ingelheim, Bristol Myers Squibb, Castle Biosciences, Celltrion, CorEvitas, Dermavant, Dermsquared, Evommune, Forte Biosciences, Galderma, Genentech, Incyte, LEO Pharma, Mayne Pharmaceuticals, Meiji Seika Pharma, Mindera, Mirium Pharmaceuticals, Oruka, Pfizer, Sanofi-Regeneron, Revolo, Seanergy, Strata, Sun Pharma, Takeda, Trevi, and Verrica. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Standardized Incidence Ratios (SIRs) and Incidence Rates (IRs) per 100 Patient-Years (PY) of Malignant Neoplasms by Cohorta
A, Forest plot shows SIRs with 95% CIs. B, IRs per 100 patient-years of malignant neoplasms, excluding nonmelanoma skin cancer, in patients with PsO, PsA, or axSpA. Reference data are from the Psoriasis Longitudinal Assessment and Registry (PSOLAR; ranges shown for ustekinumab, infliximab, other biologics, and nonbiologics), and Vaengebjerg et al. axSpA indicates axial spondyloarthritis; PsA, psoriatic arthritis; PsO, psoriasis; RCTs, randomized clinical trials. aStandardized to the US general population using Surveillance, Epidemiology, and End Results (SEER) data.
Figure 2.
Figure 2.. Incidence Rates (IRs) of Malignant Neoplasms Across Indications by Yearly Intervals
Data points on the graphs are the IR (95% CI) per 100 PY at successive year intervals from year 0-5 (PsO), year 0-3 (PsA), or year 0-3 (axSpA). IRs across all indications throughout the time periods examined are also included. axSpA indicates axial spondyloarthritis; PsA, psoriatic arthritis; PsO, psoriasis; PY, patient-years.
See this image and copyright information in PMC

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