Conference Coverage

Checkpoint inhibitor–induced rheumatic complications have unique features



– The musculoskeletal complications of checkpoint inhibitors therapy are sometimes described as RA like, but a detailed analysis of a consecutive series of patients presented at the European Congress of Rheumatology produced the conclusion that the phenotypic expression is unique.

Dr. Alexandra Filippopoulou, a resident at the University of Patras, Greece

Dr. Alexandra Filippopoulou

“These manifestations do not necessarily include synovial involvement, so their description as a rheumatoid arthritis–like presentation is not accurate. Rather, our findings suggest the pathology is something completely different and completely new,” said Alexandra Filippopoulou, MD, a rheumatology resident at the University of Patras (Greece).

This comment was based on a prospective study evaluating musculoskeletal complications in patients treated with checkpoint inhibitors over a recent 2-year period. Of the 130 consecutive patients who received a checkpoint inhibitor in the study period, 10 (7.7%) complained of joint pain and were determined to have an inflammatory complication.

The median time to development of musculoskeletal symptoms in this mostly male patient series was 2.5 months. The site of cancer was lung in four, bladder in three, kidney in two, and skin in one. Nivolumab (Opdivo) was the most common checkpoint inhibitor used, but others were represented.

MRI studies were conducted in 8 of the 10 patients. Overall, the MRI studies showed more myofascial than synovial involvement, but Dr. Filippopoulou described three distinct patterns.

In four patients, there was prominent periarticular involvement marked by diffuse swelling in the hands, feet, knees, or a combination of these joints. Synovitis, when observed, was mild, but myositis and fasciitis were common in adjacent tissues.

In three patients with a chief complaint of knee pain, myofasciitis was prominent in the surrounding muscles. Again, synovitis, when observed, was mild. It was unclear whether a partial tear of the quadriceps tendon observed in one patient was checkpoint inhibitor related.

In a third pattern, shared by three other patients, synovitis was prominent, but so was myositis in adjacent muscles. In two of these patients, the inflammatory activity was confined to the hands; in the third, both the knees and the ankle were also involved.

Regardless of these patterns of inflammation, “almost all of these patients continued to show good range of motion, which is not something that is commonly seen in patients with rheumatoid arthritis,” Dr. Filippopoulou observed.

Overall, the joint pain tended to be mild to moderate. They all responded well to low-dose glucocorticoids or analgesics without need to discontinue the anticancer therapy, Dr. Filippopoulou reported.

Not least interesting of the findings, 50% of the patients with musculoskeletal adverse events had a favorable response to the checkpoint inhibitor therapy, compared with just 12.5% of patients without these complaints, a difference that reached statistical significance (P = .0016), according to Dr. Filippopoulou. This observation is consistent with a study published last year that also associated immune-related adverse events with a greater likelihood of an anticancer response (Ann Rheumatic Dis. 2018;77:393-8).

“This is an interesting finding, but the theory that musculoskeletal adverse events predict a better response to checkpoint inhibitor therapy needs to be proven,” she said.

A larger case series is needed to better characterize joint inflammation associated with checkpoint inhibitors, but Dr. Filippopoulou concluded from her series that these adverse events are not accurately described as RA like. Rather, the phenotypic expression appears to be unique, not fully resembling any other joint pathology.

Dr. Filippopoulou reported no potential conflicts of interest.

SOURCE: Filippopoulou A et al. Ann Rheum Dis. Jun 2019;78 (Suppl 2):251. Abstract OP0335. doi: 10.1136/annrheumdis-2019-eular.5029.

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