How to treat immunotherapy induces arthritis?

Treatment of arthritis induced by immunotherapy (immune checkpoint inhibitor-induced arthritis, irAE-arthritis) involves a graduated approach based on severity and response to initial treatment.

For mild cases, initial management should begin with symptomatic treatment including nonsteroidal anti-inflammatory drugs (NSAIDs) and/or analgesics, which may provide adequate relief without interrupting cancer immunotherapy. In cases of monoarthritis or oligoarthritis, intra-articular corticosteroid injections can be considered to target localized inflammation Kostine et al. 2021 Gao et al. 2025.

When symptoms are moderate to severe or not controlled adequately with symptomatic therapy, systemic glucocorticoids are recommended, typically starting at moderate doses such as 10-20 mg/day prednisone equivalent, aimed at rapid inflammation control while tapering to the lowest effective dose (usually ≤10 mg/day) to minimize impact on antitumor immunity and avoid long-term steroid complications NICE NG100 Kostine et al. 2021 Gao et al. 2025.

If arthritis is insufficiently responsive to glucocorticoids, or if long-term steroid-sparing is required, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) such as methotrexate, hydroxychloroquine, or sulfasalazine should be considered. Methotrexate is often favored due to evidence of efficacy and safety, including in the immunotherapy context, although caution is advised with sulfasalazine due to potential hypersensitivity reactions Kostine et al. 2021 Gao et al. 2025 NICE NG100.

In patients with severe or refractory irAE-arthritis that does not adequately respond to csDMARDs and glucocorticoids, biologic DMARDs (bDMARDs) are indicated, with tumor necrosis factor (TNF) inhibitors and interleukin-6 receptor (IL-6R) inhibitors being the preferred options. The use of TNF inhibitors such as infliximab or adalimumab has shown good efficacy in controlling severe arthritis without clearly compromising anticancer effects Kostine et al. 2021 Gao et al. 2025. IL-6R inhibitors such as tocilizumab have also been successfully applied with rapid clinical improvements and appear to preserve antitumor immunity Kostine et al. 2021 Gao et al. 2025.

Emerging targeted synthetic DMARDs, such as Janus kinase (JAK) inhibitors, hold promise due to their role in key cytokine signaling (notably IL-6 and IFN pathways) involved in irAE-arthritis pathogenesis; these agents are under investigation but not yet established as standard care Gao et al. 2025.

High-dose glucocorticoids (e.g., methylprednisolone pulses) and other immunosuppressants like abatacept should generally be reserved for life-threatening or severe cases such as myositis, given concerns about potential interference with antitumor effects and lack of broad evidence for routine use in isolated arthritis Kostine et al. 2021 NICE NG100.

Therapeutic decisions, including holding or continuing immunotherapy, should be individualized based on arthritis severity, immunosuppressive requirements, oncologic response, and patient preferences, favouring a shared decision-making approach involving oncologists and rheumatologists Kostine et al. 2021 NICE NG100.

Notably, new randomized trials such as the REACT trial are underway to assess frontline use of anti-TNF therapy (adalimumab) without glucocorticoids, aiming to achieve faster remission, reduce steroid exposure, and minimize immunosuppression-related adverse effects in irAE-arthritis, though results are pending Fisher et al. 2026 Gao et al. 2025.

Overall, the escalation of treatment starts with NSAIDs and local steroids, proceeds with systemic glucocorticoids if needed, followed by csDMARDs for steroid sparing or refractory disease, and advances to bDMARDs (TNF or IL-6 inhibitors) for severe or persistent cases, always balancing control of arthritis with the preservation of immunotherapy efficacy NICE NG100 Kostine et al. 2021 Gao et al. 2025.