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Higher malignancy risk with JAK inhibitors in rheumatology compared TNF inhibitors

The malignancy risk across all indications is higher with janus kinase inhibitors than tumour necrosis factor inhibitors

Janus kinase inhibitor (JAK inhibitors) use is common for a range of rheumatic conditions. However, prior data suggests an elevated malignancy risk with the Janus kinase inhibitor tofacitinib than with a tumour necrosis factor inhibitor (TNFi). In contrast, a recent and real-world data analysis was unable to detect a higher cancer risk with JAK inhibitors.

At the British Society for Rheumatology Conference 2023, UK researchers undertook a meta-analysis of the malignancy risk with JAK inhibitors. The analysis examined the risk of all JAK inhibitors with other agents such as TNFi and methotrexate (MTX). Researchers sought phase 2/3/4 randomised trials and long-term extension (LTE) studies. The JAK inhibitors were tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib. Studies examining the drugs in rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, or atopic dermatitis were included. The researchers used the incidence of malignancy as their primary outcome. Secondary outcomes were either non-melanoma skin cancers (NMSCs) or malignancies excluding NMSCs.

Malignancy risk and JAK inhibitor use

Data from a total of 62 RCTs and 14 LTE studies were eligible for analysis. There were 71,767 person-years of exposure to JAK inhibitors, 2,680 to placebo, 7,827 to TNFi and 1,074 to MTX.

The incidence rate ratio (IRR) for malignancy risk in JAKis compared to placebo, including NMSCs was non-significant (IRR = 0.81, 95% CI 0.52 – 1.26, p = 0.36). Similarly, for JAKis and MTX (IIR = 0.73, 95% CI 0.33 – 1.61, p = 0.43).

In contrast, compared with TNFis, use of a JAKi was associated with a higher malignancy risk (IRR = 1.54, 95% CI 1.19 – 2.01, p = 0.001). These findings were consistent for the secondary analyses, i.e., when analysing NMSC only, excluding NMSC and when including LTE data.

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