Immune checkpoint inhibitors (ICI) have demonstrated improvement in overall survival across a range of tumor types. However, ICI therapy is associated with severe immune related adverse events (irAEs) including inflammatory arthritis. Here, we report our experience for rheumatological irAEs in patients with and without pre-existing auto-immune disease (AID).
Data was collected retrospectively for 15 patients identified as having rheumatological irAEs secondary to ICI therapy in our center between 2015-2019. We identified three patients with pre-existing AID.
The mean age of the cohort was 66 years.The commonest tumour types were melanoma (73%) and NSCLC (27%). In the group without AID, (n=12), 7 patients developed inflammatory arthritis (IA). Two patients with PMR like syndrome depicted typical clinical phenotypes supported by raised inflammatory markers. The SICCA syndrome patient had biopsy proven lichenoid drug eruption and feature of xerostomia. One patient had synovial aspiration proved OA exacerbation treated with intra-articular corticosteroid injection, ceasing ICI. One patient developed grade 3 immune mediated myositis 12 days after commencing nivolumab. Muscle biopsy showed active inflammatory myopathy and lymphocytic vasculitis. Median time to any rheumatologic irAEs was 9.8 weeks. Treatment was withheld temporarily in patient and it was stopped permanently in 2 patients. All patients had high doses of glucocorticoids that led to significant, moderate and minimal improvement in 2, 8 and 2 patients, respectively. Additionally, 3 patients needed other disease modifying anti-rheumatoid drugs (DMARDs). In cohort with pre-existing AID (n=3), only patient with rheumatoid arthritis (RA), had flare of RA after 7 weeks of initiating ICI therapy. ICI therapy was withheld and had resolution of symptoms with steroids.
Rheumatic irAEs are serious and less understood adverse events secondary to ICI therapy requiring steroids and additional immunosuppressive therapy. Future studies should aim at defining the type of rheumatologic irAEs experienced in trials patients and response to steroids +/- DMARDs. A mutli-disciplinary approach is recommended.
Dr. Azim Khan.
Has not received any funding.
All authors have declared no conflicts of interest.