Johns Hopkins University researchers have found a link between cancer immunotherapy drugs and an increased risk of developing rheumatologic disorders, which they expect to only be exacerbated as their use increases. They conducted what’s thought to be the largest published study of patients taking immunotherapies aimed at examining the potential connection between the drug class and these sorts of diseases.
In a review of patients taking cancer immunotherapy drugs at the Johns Hopkins Hospital from 2012 to 2016, about 1.3% of patients treated with immunotherapy drugs, either alone or in combination, reported a subsequent rheumatologic disease. That’s a higher than normal risk, based on the 13 reported patients, the researchers said.
“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 Dr. Laura Cappelli, a rheumatologist at the Johns Hopkins University School of Medicine, in a statement.
She said that if further research can confirm a cause-and-effect relationship, this study’s findings may be underestimating how common rheumatologic diseases are in patients taking immune checkpoint inhibitors. Cappelli expects that some symptoms, such as mild joint pain, may not have been diagnosed correctly.
Cappelli would like to see more physicians and patients more closely weighing the potential risks and benefits of these drugs—and for patients who do opt to use them to be watchful for rheumatologic symptoms so that they can attempt to gain treatment to try to prevent or limit joint damage.
The 13 patients treated at the Johns Hopkins Kimmel Cancer Center were treated with either Yervoy (ipilimumab) or Opdivo (nivolumab) or both--both of which are from Bristol-Myers Squibb ($BMY) and were gained as part of its 2009 acquisition of Medarex for $2.1 billion.
These patients developed either new-onset arthritis or sicca syndrome, a set of autoimmune conditions causing dry eyes and mouth that includes Sjogren’s syndrome. The study is published in the Annals of the Rheumatic Disease.
“In 2015, our rheumatology clinic started getting more and more referrals from our oncology department to evaluate patients treated with immunotherapies,” said 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.”
Clinical trials of the drugs found an increased risk of rheumatologic and autoimmune conditions including inflammatory bowel diseases, lung inflammation, autoimmune thyroid disease and pituitary gland inflammation, the researchers noted.
“We keep having referrals coming in from our oncologists as more patients are treated with these drugs,” said Dr. Clifton Bingham, 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.”
The Johns Hopkins physicians plan to continue collaborating to better track the incidence of rheumatologic disease in patients on immunotherapy treatments to better determine whether there are particular characteristics of cancer patients that put them at a higher risk of developing subsequent rheumatologic disorders.
The research was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Jerome L. Greene Foundation.
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