Study finds rheumatoid arthritis patients have a lower risk of some immune-related adverse events than matched comparators.
Immune checkpoint inhibitors (ICI) can cause immune-related adverse events, and patients with pre-existing autoimmune disease may be at increased risk.
However, a retrospective cohort study of patients with pre-existing rheumatoid arthritis (RA) undertaking ICI therapy for cancer has suggested they are not at increased risk of immune-related adverse events (AEs) compared to similar cancer patients without RA.
“Our results suggest that pre-existing rheumatoid arthritis should not be considered a contraindication for receiving immune checkpoint inhibitors for cancer treatment,” wrote the authors, led by Dr Kaitlin McCarter of Brigham and Women’s Hospital in Boston.
The researchers included 87 RA patients from among almost 12,000 patients in data repositories who’d initiated ICI for cancer. Each RA patient was matched with up to three patients without RA based on sex, calendar year, ICI target, and cancer type and stage.
“To our knowledge, this study is the largest to date to focus on patients with a single pre-existing autoimmune condition who initiated immune checkpoint inhibitors for cancer that also includes a comparator group matched by age, sex, year, target of immune checkpoint inhibitor, and cancer type and stage,” wrote the authors in the Lancet Rheumatology.
The median age was around 71 years, 61% of participants were female and around 92% were white. The most common ICI target was PD-1 and the most common cancers were lung cancer (about half of patients) and melanoma (about one quarter). The median duration of RA was around nine years, and most patients were in remission or low disease activity upon ICI initiation.
Primary outcomes were time to mortality and time to first immune-related adverse event, and secondary outcomes were number, severity and specific types of immune-related adverse events.
Researchers found there was no difference in mortality between the two groups: among patients with RA, 69% died, compared to 63% in the comparator group. Median survival time was 13.5 months for the RA group and 17.2 months for the comparator group (a non-significant difference).
There was also no difference between the groups for more serious (grade 3 or above) immune-related adverse events (14% in the RA group vs 15% in the comparator group).
Those in the RA group were more likely to experience any-grade immune-related adverse events (61% of the RA group vs 49% of the comparator group; adjusted HR=1.72, 95%CI 1.20-2.47).
However, the difference was mainly down to RA flares: 48% of RA patients experienced flares, which were mostly mild, while 7% of the comparator group experienced inflammatory arthritis. After excluding flares and inflammatory arthritis, the RA group was significantly less likely to experience any-grade immune-related adverse events.
RA patients were at lower risk of some types of immune-related adverse events: they were significantly less likely than the comparator group to experience rash or dermatitis, endocrinopathy and hepatitis, and numerically less likely to have colitis or enteritis.
In discussing the lower rates of non-flare immune-related adverse events in the RA group, the authors suggested that “the immune system might be primed for rheumatoid arthritis flares or that treatment of flares might prevent other immune-related AE types.”
Dr David Liew, deputy chair of the international Rheumatic Immune-related Adverse Event Classification Criteria Initiative, said, “It goes to show that rheumatoid arthritis patients should get every chance at the best systemic therapy for their cancer. They deserve cancer immunotherapy when it’s warranted.
“It does behove us as rheumatologists, however, to support our patients during that inherently stressful time, to make sure we are ready to manage their RA flares if they do come up,” added Dr Liew, who is also deputy editor of Rheumatology Republic.
Excited to share our study investigating pre-existing rheumatoid arthritis (RA) and outcomes after initiation of immune checkpoint inhibitors (ICI) for cancer, led by Dr Kaitlin McCarterhttps://t.co/0Ml9tPxpu5
— Jeffrey Sparks MD MMSc (@jeffsparks) March 28, 2023
The authors acknowledged that one of the main limitations of the study was that it didn’t include patients whose oncologist didn’t initiate ICIs, perhaps because of active RA (there were few patients with moderate to high disease activity) or perceived risk of poor outcomes.
Dr Carrie Ye, of the University of Alberta, raised the issue of selection bias in an accompanying editorial and noted, “This limitation restricts the interpretation of results to only patients who were chosen by specialists to initiate immune checkpoint inhibitors, creating a circular argument for the safety and efficacy in these patients.
“To truly advocate for patients with pre-existing autoimmune disease, the question around the risk profile for those who are not offered immune checkpoint inhibitor therapy needs to be answered,” she wrote.
