Management of Pre-Existing Inflammatory Arthritis During Immune Checkpoint Inhibitor Therapy for Metastatic Renal Cell Cancer with a TNF Inhibitor for over 6 Years: A Case Report

Background The use of immune checkpoint inhibitors (ICIs) has transformed cancer care by using the body’s own immune system to target malignant cells. ICIs can cause unintended off-target effects, termed immune related adverse events (irAEs), which can be de novo or related to preexisting autoimmune diseases (PADs). Patients with PADs require close monitoring as they are at higher risk of developing de novo irAEs as well as PAD flares, which occur in over a third of patients.[1] Optimal management strategies for PAD flares, to control symptoms without negatively impacting cancer outcomes, remains unknown. Data on the long-term use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) such as TNF-inhibitors (TNFi) in patients on ICI is lacking. This case describes concomitant treatment with both an ICI and a TNFi in a patient experiencing a flare of preexisting inflammatory arthritis (P-IA).

Case Report A 57-year-old man with rheumatoid arthritis was in remission on methotrexate and a TNFi when he was diagnosed with metastatic renal cell carcinoma (RCC) and both immunosuppressives were discontinued. After failing 3 lines of therapy, he was initiated on ICI (nivolumab). Following 3 cycles of ICI he experienced a P-IA flare, which failed to respond to intraarticular glucocorticoids and methotrexate. Given the significant impact on his quality of life (QOL), a TNFi was re-initiated, his P-IA went into remission and no further irAEs developed. After a total of 78 cycles (6.5 years) of nivolumab, and palliative radiation to the bone, the patient had progression of his RCC, and the decision was made to discontinue ICI.

Conclusion This case outlines a man with metastatic RCC and P-IA who received concurrent treatment with an ICI and TNFi for over 6-years with control of his and P-IA and no other irAEs. Current guidelines for management of P-IA prior to ICI initiation recommend reducing immunosuppression to the lowest required amount or stopping it completely.[2] The optimal management of P-IA flares during ICI is less clear. Despite attempts to minimize immunosuppression, some patients will require treatment with a bDMARD to facilitate ongoing ICI and maximize QOL. A recent phase 1 clinical trial suggested that concomitant use of a TNFi and ICI may increase ICI efficacy while also preventing irAEs.[3] We hypothesize that use of the TNFi in our patients may have ameliorated the risk of developing other irAEs. Further research is needed into the safety of long-term bDMARDs use in patients receiving ICI.

References [1.] Lopez-Olivo M. Eur J Cancer 2024;207:114148. [2.] Ye C. J Rheumatol 2025;52:1207-17. [3.] Montfort A. Clin Can Res 2021;27:1037-47.