# Joint, muscle and other rheumatic side effects of checkpoint inhibitors

Source: https://onco.cc/protocols/irae-rheumatological/  
OnCo record `irae-rheumatological` (Protocol). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Immunotherapy can cause joint pain and swelling, stiffness in the shoulders and hips, a dry mouth and eyes, or, rarely, muscle inflammation. Mild cases are treated with painkillers or anti-inflammatories; others need steroids and a rheumatologist, and immunotherapy often continues. Muscle weakness, trouble swallowing or breathlessness is urgent, because muscle inflammation can affect the heart.

## Summary

Inflammatory arthritis affects 1 to 7% of trial participants; polymyalgia-like syndromes, sicca syndrome, vasculitis and myositis are less common (SITC 2021). Myositis (about 1% on PD-(L)1 inhibitors) is the dangerous one: it overlaps with myocarditis and myasthenia gravis and can involve the breathing muscles.

SITC 2021: refer grade 2 or persistent events to a rheumatologist; for arthritis, ESR, CRP, rheumatoid factor, anti-CCP, ANA, a joint count and imaging; prednisone 10 to 20 mg/day for grade 2 and 40 to 60 mg/day for grade 3 or more (LE: 1); TNF inhibitors, methotrexate, leflunomide, hydroxychloroquine, sulfasalazine or IL-6 receptor inhibitors when steroids fail or long-term treatment is needed (LE: 1). Myositis: grade 3 holds the checkpoint inhibitor and starts prednisone 1 mg/kg, with any myocardial involvement meaning permanent discontinuation.

EULAR 2021, the rheumatologists' statement, differs in emphasis: NSAIDs or analgesics first for mild to moderate symptoms; glucocorticoids only when these fail, tapered to the lowest effective dose; no methylprednisolone pulses or high-dose oral steroids outside life-threatening disease and myositis, because of concern for the anti-tumour response; a conventional DMARD when more than 10 mg/day prednisone is needed; TNF or IL-6 inhibitors preferred for refractory arthritis; holding immunotherapy as a shared decision; and withdrawal always for life-threatening myositis.

## Fields

- Kind: Protocol
- Last checked: 2026-11-11
- Also known as: checkpoint inhibitor arthritis; ICI inflammatory arthritis; rheumatic irAEs; immune-related polymyalgia rheumatica; checkpoint inhibitor myositis; immune-related sicca syndrome; musculoskeletal irAEs
- Tags: protocol; irae; rheumatology

## Connected records

- protocols: [Immune-related myocarditis from checkpoint inhibitors](https://onco.cc/protocols/irae-myocarditis/), [Neurological side effects of checkpoint inhibitors: myasthenia gravis, Guillain-Barré syndrome, meningitis and encephalitis](https://onco.cc/protocols/irae-neurological/)
- ideas: [Treat immunotherapy side-effects without wiping out the response](https://onco.cc/ideas/idea-bio2-steroid-sparing-irae/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Avelumab](https://onco.cc/drugs/avelumab/), [Cemiplimab](https://onco.cc/drugs/cemiplimab/), [Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Human normal immunoglobulin (IVIg)](https://onco.cc/drugs/human-normal-immunoglobulin/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Prednisone](https://onco.cc/drugs/prednisone/), [Tocilizumab](https://onco.cc/drugs/tocilizumab/), [Tremelimumab](https://onco.cc/drugs/tremelimumab/)
- institutions: [American Society of Clinical Oncology (ASCO)](https://onco.cc/institutions/asco/), [European Society for Medical Oncology (ESMO)](https://onco.cc/institutions/esmo/), [Society for Immunotherapy of Cancer](https://onco.cc/institutions/sitc/)
- terms: [Immune-related adverse events (irAEs)](https://onco.cc/terms/irae/)
- key papers: [ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors](https://onco.cc/key-papers/paper-asco-irae-guideline-jco-2021/)

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