From the Guidelines
Immune checkpoint inhibitors (ICIs) are associated with a significant risk of rheumatic complications, including inflammatory arthritis, polymyalgia rheumatica-like syndromes, myositis, vasculitis, sicca syndrome, and lupus-like conditions, affecting approximately 10% of patients receiving these therapies 1.
Key Considerations
- The risk of rheumatic complications varies by medication, with CTLA-4 inhibitors generally causing more severe reactions than PD-1/PD-L1 inhibitors 1.
- These complications can occur at any time during treatment, even after discontinuation, and typically develop within 3-6 months of starting therapy 1.
- Management depends on severity, ranging from symptomatic treatment with NSAIDs and low-dose corticorticoids for mild cases to higher-dose corticorticoids for moderate cases, and may require temporary or permanent ICI discontinuation and immunosuppressive therapy for severe cases 1.
Rheumatic Complications
- Inflammatory arthritis: resembling rheumatoid arthritis or spondyloarthritis, with symptoms including joint pain and swelling 1.
- Polymyalgia rheumatica-like syndromes: characterized by severe myalgia in the proximal upper and lower extremities, with severe fatigue 1.
- Myositis: a rare but potentially severe complication, with symptoms including weakness, primarily in the proximal extremities, and myalgia 1.
Management
- Symptomatic treatment with NSAIDs and low-dose corticorticoids is recommended for mild cases, while higher-dose corticorticoids and immunosuppressive therapy may be necessary for moderate to severe cases 1.
- Temporary or permanent ICI discontinuation may be required for severe cases, and the decision to hold or continue cancer immunotherapy should be based on the severity of rheumatic immune-related adverse events, tumor response, and future oncology treatment plan 1.
Patient Monitoring
- Regular assessment for joint pain, muscle weakness, dry eyes/mouth, and other rheumatic symptoms is essential during ICI therapy 1.
- Patients with pre-existing autoimmune conditions have a higher risk of rheumatic complications and require careful monitoring 1.
From the Research
Risk of Rheumatic Complications
The use of Immune Checkpoint Inhibitors (ICIs) has been associated with significant immune-related adverse events (irAEs), including rheumatic complications.
- Rheumatic irAEs can be categorized into de novo toxicity and flares of pre-existing rheumatic conditions 2.
- The onset of de novo toxicity often occurs late into treatment, while flares of pre-existing rheumatic conditions occur shortly after ICI initiation 2.
- Management of rheumatic irAEs often requires systemic or intra-articular steroids, as well as disease-modifying anti-rheumatic drug (DMARD) therapy in some cases 2, 3.
Prevalence of Rheumatic irAEs
- The prevalence of arthralgia and myalgia in patients treated with ICIs has been reported to be common, ranging from 1-43% and 2-20%, respectively 4.
- The prevalence of rheumatic irAEs such as inflammatory arthritis, vasculitis, and sicca syndrome is less clear from current evidence 4.
- A study found that 32% of patients with rheumatoid arthritis (RA) developed immune-related adverse events (irAEs) after initiating ICI treatment, with 9% developing grade 3 (severe) irAEs 5.
Management and Treatment
- The management of ICI-induced rheumatic irAEs includes the use of glucocorticoids, disease-modifying antirheumatic drugs (DMARDs), and biological agents 3.
- A personalized approach to optimized combined therapy may be necessary to manage ICI-induced rheumatic irAEs, including the use of an ex vivo diagnostic assay to select the most effective ICI and antirheumatic drug combinations 3.
- Close collaboration between oncologists and rheumatologists is advisable when considering ICIs in patients with pre-existing rheumatic conditions, such as RA 5.