A case report of a patient with rheumatoid arthritis induced by checkpoint inhibitor treatment

Abstract

Malignant melanoma occurs for only 1% of all skin neoplasms, but is characterized by the most aggressive clinical course and the lowest 5-year survival rate.  Even after radical resection of patients in the non-metastatic stage, there is an increased risk of local recurrence and distant metastasis. Advances in molecular biology have aided the development of innovative targeted- and immunotherapies that have greatly improved patient prognosis. Among them is the suppression of the immune response through the expression of the transmembrane protein PD-L1 on the surface of neoplastic cells. Nivolumab is a humanized monoclonal antibody (so-called immune "check point" inhibitors), first-line treatment in patients with metastatic malignant melanoma and also used as an adjuvant treatment in patients at high risk of relapse, which is associated with PD-1 and therefore supports the inhibited T-cell immune response. This in turn leads to the risk of various autoimmune life-threatening adverse reactions. In clinical studies, immune-related adverse events of various degrees and severity have been described with the use of anti-PD-1 antibodies - immune-mediated colitis, pneumonitis, nephritis, hepatitis, dermatitis, arthritis, myositis, vasculitis, polymyalgia rheumatica, eosinophilic fasciitis and scleroderma. In rheumatology practice, the most frequently described cases of arthritis occur after a different period of time from the start of Nivolumab therapy. The specific mechanisms of the onset of immune-mediated arthritis in anti-PD-1 antibody therapy are not fully understood, but an overlapping pathogenesis with the onset of rheumatoid arthritis is suggested – PD-1 expression in the synovial fluid is a proven regulator of the T-cell immune response and is a possible future target for immunomodulatory therapy of rheumatoid arthritis (RA). We present a clinical case of a 52-year-old patient who developed RA following Nivolumab treatment. After temporarily discontinuation of Nivolumab, Methotrexate therapy was started and the patient showed a good clinical response after 3 months and reached minimal disease activity.