Checkpoint Inhibitors Causing Arthritis Save

A recent report from Johns Hopkins, published in the Annals of Rheumatic Diseases, describes 13 cancer patients treated with the immune checkpoint inhibitors, ipilimumab or nivolumab, who developed inflammatory arthritis and sicca syndrome. This is another collection of musculoskeletal (MSK) complications associated with the use of checkpoint inhibitors. 

Immune checkpoint inhibitors (ICIs) target the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways and have been effective in treating multiple advanced cancers. They have also resulted in immune-related adverse events (IRAEs), that only recently has included MSK adverse events. 

Chronic arthritis is another to be added to a growing list of IRAEs associated with the ICIs, including pneumonitis, colitis, hypothyroidism, and hepatitis, as well as inflammatory problems in the pituitary, skin, eye, kidney, pancreas, and CNS.

These patients were being treated with ipilimumab monotherapy (five patients) or a combination of ipilimumab and nivolumab (eight patients) for a variety of solid tumors, including melanoma, non–small cell lung cancer, small cell lung cancer, and renal cell carcinoma. The average age of the patients was 58.7 years, and were 83% men.

Nine patients developed inflammatory arthritis, involving large and small joints. In some this was RA-like polyarthritis, but in others fit a pattern more consistent with reactive arthritis or spondyloarthritis. In all, the arthritis was highly inflammatory, with 6 patients developing a rheumatoid arthritis–like disease. Four patients also developed sicca syndrome, with abrupt, severe salivary hypofunction and less severe dry eye symptoms.

Five of these patients were treated with systemic prednisone at a dosage of up to 120 mg daily, a much higher dosage than is usually needed to control inflammatory arthritis.