Nivolumab or Ipilimumab Treatment May Increase Risk of Developing Autoimmune Joint and Tissue Disease
Case reports on 13 patients with cancer suggest that patients taking the immunotherapeutics ipilimumab (Yervoy) and nivolumab (Opdivo) may be at higher-than-normal risk of developing autoimmune joint and tissue diseases, including inflammatory arthritis, according to a preliminary study by Johns Hopkins Medicine researchers. The cases they followed were reported by Cappelli et al in the Annals of the Rheumatic Diseases.
“I don't think anyone is particularly surprised that rheumatologic disorders might be a complication of drugs that boost the immune system,” said study author Laura C. Cappelli, MD, a rheumatologist at the Johns Hopkins University School of Medicine. But the new study, however small in sample size, she said, is believed to be the largest published case series of a link between the drugs and the diseases.
The patients described in the new case report make up only about 1.3% of the total patients treated with drugs—singly or in combination—at The Johns Hopkins Hospital from 2012 to 2016, Dr. Cappelli said. Nevertheless, if further research confirms a cause-and-effect relationship, the rate is likely an underestimation of how common rheumatologic diseases are in patients taking immune checkpoint inhibitors. She noted that patients with only mild joint pain, for instance, or those with already deteriorating health from their cancers, may not have been referred to the rheumatology clinic for their symptoms.
“We keep having referrals coming in from our oncologists as more patients are treated with these drugs,” said Clifton Bingham, MD, Associate Professor of Medicine at the Johns Hopkins University School of Medicine and Director of the Johns Hopkins Arthritis Center. “In particular, as more patients are treated with combinations of multiple immunotherapies, we expect the rate to go up.”
Study Details
Between 2012 and 2016, 13 patients at the Johns Hopkins Kimmel Cancer Center who were taking one or both drugs to treat their cancers developed new-onset arthritis or sicca syndrome, a set of autoimmune conditions causing dry eyes and mouth, including Sjogren’s syndrome.
“In 2015, our rheumatology clinic started getting more and more referrals from our oncology department to evaluate patients treated with immunotherapies,” said Dr. Cappelli. “And the patients we saw had very severe, highly inflammatory arthritis. They needed even higher doses of steroids to control their symptoms compared to what is needed in other forms of inflammatory arthritis, like rheumatoid arthritis.”
Dr. Cappelli noted that clinical trials of ipilimumab and nivolumab found an increased risk of inflammatory bowel diseases, lung inflammation, autoimmune thyroid disease, and pituitary gland inflammation. But those trials were designed primarily to determine efficacy against cancer and not to fully examine all features of rheumatologic side effects, she explained.
Overall, Dr. Cappelli and her colleagues identified 13 patients who had developed previously undiagnosed or reported rheumatologic symptoms after their treatment with the immune checkpoint inhibitors. All were over age 18 and had been treated for melanoma, non–small cell lung cancer, small cell lung cancer, or renal carcinoma. Eight were taking a combination therapy with both ipilimumab and nivolumab, whereas five were taking only one of the two drugs. Nine of the patients developed inflammatory arthritis, and the other four were diagnosed with sicca syndrome. With treatment, all patients were able to get their rheumatologic diseases under control, though not eliminated completely.
Dr. Cappelli said she wants the case report to raise awareness among both patients and clinicians that rheumatologic side effects may occur with the drugs. “It is important when weighing the risk-benefit ratio of prescribing these drugs. And it’s important for people to be on the lookout for symptoms so they can see a rheumatologist early in an effort to prevent or limit joint damage.”
Funding for the studies described in the Annals of the Rheumatic Diseases article was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Jerome L. Greene Foundation.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
