Journal Article

JAK inhibitors and the risk of malignancy: a meta-analysis across disease indications

Cope, Andrew P, Stovin, Christopher, Patel, Vishit, Norton, Sam, Galloway, James B, Chan, Chun Kit David, Atzeni, Fabiola, Ng, Kenrick K H, Adeyemi, Olukemi, Russell, Mark D, Alveyn, Edward, Rutherford, Andrew I, Adas, Maryam A

2023

Overview

ObjectivesTo estimate the association of Janus kinase inhibitors (JAKi) with the incidence of malignancy, compared with placebo, tumour necrosis factor (TNF)-α inhibitors (TNFi) and methotrexate.MethodsSystematic searches of databases were performed, to December 2022, to identify phase II/III/IV randomised clinical trials (RCTs) and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) compared with placebo, TNFi or methotrexate, in adults with rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease or atopic dermatitis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy between JAKi and comparators. Bias was assessed using the Cochrane Risk of Bias-2 tool.ResultsIn 62 eligible RCTs and 16 LTE studies, there were 82 366 person-years of exposure to JAKi, 2924 to placebo, 7909 to TNFi and 1074 to methotrexate. The overall malignancy incidence rate was 1.15 per 100 person-years in RCTs, and 1.26 per 100 person-years across combined RCT and LTE data. In network meta-analyses, the incidence of all malignancies including non-melanomatous skin cancers (NMSCs) was not significantly different between JAKi and placebo (IRR 0.71; 95% CI 0.44 to 1.15) or between JAKi and methotrexate (IRR 0.77; 95% CI 0.35 to 1.68). Compared with TNFi, however, JAKi were associated with an increased incidence of malignancy (IRR 1.50; 95% CI 1.16 to 1.94). Findings were consistent when analysing NMSC only and when analysing combined RCT/LTE data.ConclusionsJAKi were associated with a higher incidence of malignancy compared with TNFi but not placebo or methotrexate. Cancers were rare events in all comparisons.PROSPERO registration numberCRD42022362630.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited,BMJ Publishing Group
• Subject: Adult / Antirheumatic Agents - adverse effects / Arthritis / arthritis, psoriatic / arthritis, rheumatoid / Arthritis, Rheumatoid - drug therapy / Arthritis, Rheumatoid - epidemiology / Atopic dermatitis / biological therapy / Cancer / Clinical trials / Disease / Drug dosages / epidemiology / FDA approval / Humans / Inflammatory bowel disease / Inflammatory bowel diseases / Inflammatory diseases / Janus kinase / Janus Kinase Inhibitors - adverse effects / Kinases / Malignancy / Meta-analysis / Methotrexate / Methotrexate - therapeutic use / Neoplasms - chemically induced / Neoplasms - drug therapy / Neoplasms - epidemiology / Placebos / Psoriasis / Psoriatic arthritis / Rheumatic diseases / Rheumatoid arthritis / Skin cancer / spondylitis, ankylosing / Surveillance / TNF inhibitors / Treatment / Tumor necrosis factor-TNF