FDA database reveals many rheumatic and musculoskeletal adverse events on immunotherapies



AMSTERDAM – Mining of the Food and Drug Administration adverse events database revealed a more substantial risk of rheumatic and musculoskeletal events on checkpoint inhibitor therapy than has been previously reported, according to Xerxes N. Pundole, PhD, an instructor in the research faculty at the University of Texas MD Anderson Cancer Center, Houston.

In a video interview, Dr. Pundole summarized data he presented at the European Congress of Rheumatology.

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So far, according to Dr. Pundole, there have been a relatively limited number of reports in the medical literature of inflammatory rheumatic or musculoskeletal events from checkpoint inhibitors. However, other inflammatory conditions, such as colitis and pneumonitis, are known to occur commonly with these agents. The FDA adverse event database provided an opportunity to evaluate how often rheumatic and musculoskeletal events are reported in the real world.

In this interview, Dr. Pundole explained that rheumatic and musculoskeletal events do occur at higher rates than would be expected in patients not treated with a checkpoint inhibitor. With data from more than 30,000 unique patients, the relative risks of some of these adverse events, such as polymyositis, were more than doubled, although the event rates were not evenly distributed.

Specifically, rheumatic and musculoskeletal adverse events were far less common with the cytotoxic T-lymphocyte antigen 4 checkpoint inhibitor ipilimumab (Yervoy) relative to programmed cell death protein 1 inhibitors, particularly nivolumab (Opdivo).

In another notable finding, a demographic stratification of the FDA database found elderly men to be overrepresented among patients developing adverse events related to musculoskeletal inflammation.

Overall, his data do support a relationship between checkpoint inhibitors and a greater risk of rheumatic and musculoskeletal adverse events than has been previously reported, but he noted that these data provide no specific guidance for those who already have RA or another inflammatory condition.

“Can you identify these adverse events early on to keep the patients on immune checkpoint inhibitor therapy and not have to stop their cancer treatment? That’s a question,” Dr. Pundole said. However, he suggested that the FDA data support clinician awareness of the problem and the studies that will establish strategies for preserving the benefit-to-risk ratio of checkpoint inhibitors in patients who are at greater risk of adverse events relative to immune function because of a preexisting inflammatory condition.

SOURCE: Pundole XN et al. Ann Rheum Dis. 2018;77(Suppl 2):147-148. Abstract OP0197.

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