Risk of Malignancy Related to Ixekizumab in Patients in Patients With Psoriatic Arthritis or Axial Spondyloarthropathy: Systematic Review and Meta-analysis.

Abstract

Background: We aimed to estimate the risk of malignancy associated with ixekizumab in randomized controlled trials (RCTs) and long-term extension studies (LTEs) in patients with rheumatological indications.

Methods: A systematic review of the literature up to June 2024 was performed to analyze the risk of malignancy associated with ixekizumab use in patients with psoriatic arthritis and axial spondyloarthritis. The primary endpoint was overall malignancy risk in RCTs and LTEs. Meta-analyses of RCTs were performed when at least 3 studies had comparable outcome measures using Peto odds ratios. For LTEs, meta-analyses were performed using random-effects computing incidence rates (IRs) per 100 patient-years.

Results: Twelve articles, 4 LTEs and 8 pooled analyses, were included. Meta-analyses of RCTs for malignancy risk at week 24 showed a Peto odds ratio of 0.45 (0.11-1.86), with an I2 of 43.0%. When stratified according to the comparator, heterogeneity decreased. Malignancy risk comparing ixekizumab with placebo was 1.43 (0.18-11.53), with an I2 of 39.6%. Malignancy risk comparing ixekizumab with adalimumab was 0.11 (0.01-0.77), with an I2 of 0%. At week 52, the IR of all malignancies with ixekizumab was 0.31 (0.07-0.72), with an I2 of 18.9%. At 156 weeks, the IR of all malignancies with ixekizumab was 0.58 (0.29-0.96), with an I2 of 0%.

Conclusion: Ixekizumab appears to confer a low malignancy risk in patients treated for rheumatological indications. Patients with psoriatic arthritis and axial spondyloarthritis appeared to be at similar risk, except for those with nonmelanoma skin cancer.