Outcomes of Patients With Rheumatoid Arthritis Initiating Immune Checkpoint Inhibitors For Cancer
In this video, Jeffrey A. Sparks, MD, MMSc, discusses his study that evaluated the outcomes of patients with pre-existing rheumatoid arthritis (RA) who initiated immune checkpoint inhibitors for cancer, if there is a mortality risk for this patient population and the research that remains on this topic.
- McCarter KR, Wolfgang T, Arabelovic S, et al. Mortality and immune-related adverse events after immune checkpoint inhibitor initiation for cancer among patients with pre-existing rheumatoid arthritis: a retrospective, comparative, cohort study. Lancet Rheumatol. Published online May 17, 2023. doi:10.1016/S2665-9913(23)00064-4
Jeffrey A. Sparks, MD, MMSc, is an associate physician and associate professor of medicine at Brigham and Women's Hospital, Harvard Medical School (Boston, Massachusetts).
Jeffrey Sparks, MD, MMSc: Hello, my name's Jeffrey Sparks. I'm a rheumatologist at Brigham Women's Hospital in Harvard Medical School in Boston, Massachusetts and I'm excited to talk about our study about outcomes of patients with preexisting rheumatoid arthritis initiating immune checkpoint inhibitors for cancer.
Consultant360: Can you tell us more about how your study came about?
Dr Sparks: Well, as many of you know, immune checkpoint inhibitors have revolutionized the cancer field and many patients are being treated with this and this leaves patients with autoimmune diseases such as rheumatoid arthritis in a bit of a bind because they might have a more propensity to develop immune-related adverse events as a consequence of the immune stimulation from these immune checkpoint inhibitors. Certainly, we're seeing more and more of these patients as the medications are being used more for cancer so we felt that there was a lot of unanswered questions about how these medications might affect risk for flare of rheumatoid arthritis, as well as other types of immune-related adverse events and even mortality.
C360: How do your results impact clinical practice?
Dr Sparks: Well, we first found that patients with preexisting rheumatoid arthritis were at increased risk of immune-related adverse events. However, we found that really the only type of adverse event that patients were at risk for were RA flares so we were really worried about severe immune-related adverse events and different organs. For example, pneumonitis can be quite severe. Some patients need to get admitted, get high doses of steroids, stop their checkpoint inhibitor, and some patients even die. We were a bit worried that the RA patients may be at more risk of this given their underlying immune autoimmune condition.
I think reassuringly, we actually found that patients with preexisting rheumatoid arthritis were not at increased risk for other types of immune-related adverse events, and also had no increased risk for severe immune-related adverse events. I think this is reassuring, letting patients know that certainly, RA flares are more likely, but other organs are relatively less likely to have bad outcomes.
We also were interested to see how patients with preexisting rheumatoid arthritis did related to mortality. You could imagine that these patients may not respond quite as well to the checkpoint inhibitors or again, that the adverse events could put them at risk for lethal complications. Again, reassuringly, we found that there was actually no difference between mortality between the RA cases and their comparators, such that it seems that these drugs work probably just as well in this patient population and certainly the side effects don't put them at risk for bad outcomes. Overall, we feel like this is very reassuring data to help reassure RA patients, rheumatologists, and oncologists that patients can receive these medications safely.
C360: How do the results of your study impact the multidisciplinary care of patients with RA and cancer?
Dr Sparks: Certainly, patients with preexisting autoimmune diseases such as rheumatoid arthritis are particularly complex when thinking about cancer treatment. Certainly, it's already a complex decision about how to stage cancer and what appropriate treatments there are, and to also put on top of that an underlying autoimmune disease that often needs systemic immune suppression, you can see that there'd be a lot of complexity to sort out between patients, oncologists, and rheumatologists. We feel that this adds really helpful data that certainly the RA flare is something to monitor closely for, however, most of the flares were mild and relatively easily managed, and these patients didn't have a difference in more mortality and didn't have a difference in severe immune-related adverse events so we feel like this will be helpful data to help tell patients to know what to expect and to also encourage appropriate treatment of checkpoint inhibitors for patients with underlying autoimmune diseases such as rheumatoid arthritis. However, certainly there's much more work to be done, particularly related to patients with high disease activity from RA patients who are requiring relatively more potent immune suppression. Many of the patients that were in our study had either no disease activity or low disease activity, and many of them had stopped their DMARDs, presumably due to preceding chemotherapy. There's still more work to be done in some patients who have more severe and active rheumatoid arthritis.
C360: What other knowledge gaps exist in this area?
Dr Sparks: Well, certainly this is a good first step related to some reassurance for these patients. However, we only studied rheumatoid arthritis patients, so you wonder about different diseases such as systemic lupus, multiple sclerosis, inflammatory bowel disease, and certainly you wonder about specific medications. Perhaps there are some patients who are on specific immune suppressants that might have a different outcome compared to the study that we performed. And then patients who actually have a lot of RA disease activity, there weren't many in our study, so you certainly wonder, and patients who are very active and need immune suppression to control their underlying RA, how those patients might do relatively differently than patients in our study that were relatively better controlled. Certainly, future studies are needed and prospective studies are needed to understand some of the biologic mechanisms and understand some of the immune pathways that are activated in patients with underlying autoimmune diseases.
C360: What is the next step in this research?
Dr Sparks: From our point of view, there's many more steps for this types of research. First, we mostly focused on the comparison between RA patients and comparators. We think that actually analyzing only the RA patients also has a lot to offer. First off, related to how to manage flares from checkpoint inhibitors, whether there's specific medications that might have more efficacy or safety, and how the treatment of the flares might impact other immune-related adverse event risk, as well as response to the checkpoint inhibitor. Certainly, we'd like to look at other patient populations besides rheumatoid arthritis, expand this to other immune-mediated inflammatory diseases, also focus on specific medications that may alter the course such as targeted therapies. Then we need prospective research studies, both to understand the biologic mechanisms of immune-related adverse events from these medications and at the end of the day, to really understand how to treat these patients, we would need trials to understand both the safety and efficacy of different treatment modalities for flare of underlying rheumatic diseases such as rheumatoid arthritis.
C360: What is the overall take-home message from your study?
Dr Sparks: Overall, we feel that our results were fairly compelling about reassuring patients who have preexisting rheumatoid arthritis that their outcomes are overall quite good. Besides an increased risk for mild rheumatoid arthritis flares, our patients had no increased risk for severe immune-related adverse events. They actually had lower risk for other types of immune-related adverse events, and there was no impact of having preexisting RA on mortality. To us, this suggests that patients with preexisting rheumatoid arthritis should not be considered to be a contraindication to appropriate treatment immune checkpoint inhibitors for cancer treatment.
Dr Sparks: Thanks again for your interest in our study and we'll look forward to follow-up studies to delve more deeper into this research topic.
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