Immunotherapy-Induced Arthritis: An Update

Lara C. Pullen, PhD

Disclosures

February 06, 2019

Editorial Collaboration

Medscape &

Anne R. Bass, MD, is a rheumatologist at the Hospital for Special Surgery (HSS) in New York City, where she, among other things, studies the autoimmune effects of cancer immunotherapy. Medscape spoke with Dr Bass to get the latest information on checkpoint inhibitor–induced arthritis, and how her research is helping facilitate an important discussion between rheumatologists and oncologists.

Anne R. Bass, MD

Medscape: I know you spoke with Medscape last year about immunotherapy arthritis. Can you give us an update? What you have learned over the past year?

Bass: Sure. Over the past year there have been a slew of publications describing experience at different institutions with immunotherapy-induced arthritis. So, we now have larger numbers and a better—but still not complete—idea of what the arthritis looks like clinically. These publications from multiple centers have given us a better sense of the way that arthritis presents.

Our institutions are just beginning to develop infrastructure to be able to collect blood and synovial fluid from patients. This will allow us to begin to understand the biology that underlies the arthritis. This is important because so far there is actually very little that's been written about that.

There was one poster[1] at the American College of Rheumatology meeting describing a synovial biopsy from a patient with checkpoint inhibitor–induced arthritis. The authors demonstrated that the checkpoint inhibitor–induced arthritis had many features on simple stains that resembled rheumatoid arthritis. That poster has some of the first information, on a biological level, about how this kind of arthritis presents.

Medscape: How common is checkpoint inhibitor–induced arthritis?

Bass: I think the best estimate comes from a study by Marie Kostine[2] in a center in France where they had 500 patients who received immunotherapy. They asked oncologists to refer their patients if they developed arthritis. So, it wasn't a prospective study by rheumatologists, but it determined that 3.8% of the patients developed an inflammatory arthritis. It's not a huge number, but it's not 1% either.

Medscape: Right. I was going to say that it's not trivial.

Bass: No, it's not. I expect, though, that there was a larger number that probably developed joint pain without swelling. Patients often have more than one complication of immunotherapy at the same time. So if they developed another complication and they received steroids for that other complication, then the steroids can mask the symptoms of arthritis. My guess is that it's closer to 5%.

Medscape: How long would a patient typically be on one of these checkpoint inhibitors?

Bass: It varies. In the case of patients who have melanoma, which is the cancer in which the immunotherapy agents have been used the longest, they'll often receive combination therapy with a medicine called ipilimumab, which blocks the molecules called CTLA-4, and another medicine that blocks the molecule, called PD-1.

In the protocol, they'll often want patients to stay on treatment for a year or 2 years, but many patients have to stop therapy earlier because of adverse events. I think what we're seeing is that the longer you stay on them, the more likely you are to have an adverse event, including arthritis.

Medscape: It seems to me that even after the medication has been stopped, the patients still have an immune response.

Bass: Right. Most of the time they develop symptoms while they're on the medication, but we have seen patients who have developed arthritis symptoms after they have stopped—even a year after. I think the key difference between arthritis and other adverse events that we're beginning to recognize is that the arthritis doesn't tend to go away. So, if you develop colitis— diarrhea colitis from immunotherapy—you're treated for it for 4-6 weeks and it usually goes away. Then you can often resume the immunotherapy. The arthritis doesn't seem to go away. Even in people in whom we stopped the immunotherapy, the arthritis seems to persist, and I would say that persisting is more common than not persisting.

Medscape: What about managing the patients?

Bass: There are treatment algorithms, but the ones that are published are really for what you do on day 1. There's nothing published about what to do in month 2, and as I said, these patients often have a persistent arthritis. So, we here at HSS have created a treatment algorithm for going forward. It depends on the grade of the arthritis. We usually start with steroids, but for those with high-grade arthritis, we move quickly to TNF inhibitors.

Medscape: Is your algorithm published?

Bass: We'll be publishing it soon.

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