A New Rheumatic Disease?

A Conversation With Physician and Researcher Dr Anne Bass

Bret S. Stetka, MD

Disclosures

November 30, 2017

Editorial Collaboration

Medscape &

Dr Anne R. Bass keeps busy. A rheumatologist at the Hospital for Special Surgery (HSS) in New York City, she is involved in diverse research projects, from exploring disparities in orthopedic surgery outcomes to studying the autoimmune effects of cancer immunotherapy. While in San Diego attending the American College of Rheumatology (ACR) 2017 Annual Meeting, Medscape spoke with Dr Bass about her research and highlights from this year's conference.

Medscape: Please tell us about some of the research you'll be presenting at the ACR meeting this year.

Dr Bass: Along with one of our trainees, Melanie Smith, I'm presenting a series of patients who have received cancer immunotherapy and developed arthritis as a result. This is new rheumatic disease that develops in patients who are receiving the new immunotherapy medications that modulate the immune system to treat cancer. The drugs induce the patients' own immune systems to attack cancer, but one of the side effects is that they can develop autoimmunity.

We're only just beginning to understand these conditions and how to manage them. Our presentation describes an early series of patients who developed an inflammatory arthritis after being treated.

Medscape: So these are such drugs as checkpoint inhibitors and CAR T-cell therapies?

Dr Bass: Exactly. There are some prototypical reactions to checkpoint inhibitors that lots of patients get: colitis, for example, and skin reactions. But we wanted to better characterize the arthritis that can also occur, and whether or not everyone gets the same type of symptoms. In fact, they don't. Some develop a rheumatoid arthritis-like pattern of disease activity, whereas some develop something more like polymyalgia rheumatica.

It seems that these medications are unleashing conditions that the patient might be genetically predisposed to in a nonspecific way. I think that these conditions may serve as a natural model of how some of our diseases develop.

Medscape: If a patient is on an effective immunotherapy but develops arthritis, how do you and the oncology team proceed? Do you leave them on the medication and try to treat the arthritis?

Dr Bass: It really depends on how severe the side effects are. In some patients, we continue the immunotherapy and they can be managed with small doses of prednisone. Other patients actually have to stop immunotherapy and be treated more aggressively. Of note, that doesn't always mean that their cancer comes back. In some of the melanoma trials, it's been shown that some patients who receive only one dose of a checkpoint inhibitor go into sustained remission.

That said, we and the oncologists follow the patients closely, and if they have cancer progression, they can be put back on the immunotherapy or switched to something else. We don't have an oncology division at HSS, but Memorial Sloan Kettering is right across the street from us, and we serve as their rheumatologists—there's plenty of opportunity for collaboration with them.

Medscape: Tell us about some of your other research being presented this week.

Dr Bass: Another area that I'm very interested in is predictors of poor outcomes after arthroplasty. We have a presentation here on the interaction between community poverty and levels of education, and their effects on patient reported outcomes after arthroplasty.

Whereas in wealthy communities, education level doesn't have much of an impact [on patient outcomes], in poor communities the level of education has a profound effect on outcomes. So there's a synergy between education and community poverty. We previously showed a similar interaction between race and poverty, in which the impact of race is great in poor communities but fairly minimal in wealthy communities.

Medscape: What other factors have you uncovered that lead to poor outcomes or better outcomes after arthroplasty?

Dr Bass: The patient's physical status before surgery is probably the strongest predictor of poor outcomes—the worse joint pain and function are going into surgery, the worse these outcomes will be coming out. You get great benefits from the intervention, but if you start off worse, you end up worse, which is not entirely surprising.

Related to this, I think one of the mechanisms behind the racial and social disparities in outcomes may be that those who are less educated may postpone their surgeries. So they have worse functional status before surgery, and that may lead to worse outcomes. Then there's a vicious cycle in which those living in poor communities look at their peers and see bad outcomes, so they postpone own surgery. And that in turn leads to worse outcomes.

Medscape: You also do a lot of research around education, correct?

Dr Bass: Yes. I'm the chair of the Committee on Training and Workforce for the American College of Rheumatology, and we at HSS have a few posters this year on education. One relates to an initiative called "CLASS-Rheum," which stands for "Clinical Literature Assessment Skills Support-Rheumatology."[1]

This is the work of Lisa Mandl and Juliet Aizer, two of my colleagues at HSS. They both have advanced training in epidemiology and statistics and have done a great job of training our trainees in statistical methods.

They recognized that there is a need for this kind of training, so they've created an interactive modular curriculum to teach basic statistical principles to fellows. They piloted this in several institutions across the country and demonstrated both acquisition of knowledge and satisfaction on the part of the trainees and the program directors. Because many centers don't have a strong research component to their departments, there often aren't trained faculty to teach this. So the hope is that after launch, this curriculum will be implemented widely.

I would say that HSS has really been at the forefront of educational research such as this.

Other Meeting Highlights

Medscape: What are some of the general areas of research being presented at this year's meeting that you're most excited about?

Dr Bass: I think we're always excited to hear about new developments in the treatment of inflammatory arthritis. I'm always hopeful that there will be something for scleroderma and for lupus.

My colleague Rob Spiera has a nice phase 2 study[2] of a cannabinoid for scleroderma that looks promising. There have been so many trials in scleroderma that have shown promise and then failed in phase 3 trials, so hopefully this one will pan out.

Medscape: As always, a lot is being presented here this week on biosimilars. What are your thoughts on how promising these new drugs look?

Dr Bass: I think the big story about biosimilars is that the price isn't anywhere as low as it should have been, so I think that there's a lot of anxiety about biosimilars. They're only around 15%-30% cheaper than the branded drugs—which, when dealing with drugs this expensive, is still a lot of money.

But I'm not as worried about them as other people are. I think we've learned that even the composition of the reference drugs has changed over time—that modifications happen from batch to batch throughout the years. It's important to remember this when worrying about differences between biosimilars and parent compounds.

I certainly understand the anxiety around biosimilars, but my greatest anxiety is around the sustainability of our healthcare system, and anything that can bring down cost and make drugs more available to patients would be a very good thing.

Medscape: There is a lot of talk this year about precision medicine, in many fields. What are your thoughts on where precision rheumatology stands?

Dr Bass: I think personalized or precision medicine is an exciting new area. We're starting to better understand rheumatoid arthritis and lupus on a case-by-case basis at the molecular level, but I think this work is in its infancy. It's kind of where the Human Genome Project was 10 years ago, and where 19th-century biologists were when they were collecting detailed data about plants and animals in the forest—that is, we're describing patients' blood and tissues on a detailed molecular level, but we have yet to apply that knowledge to patient management. But I think it's exciting, and I think will lead to great discoveries.

Medscape: Are there any precision treatments yet in rheumatology?

Dr Bass: I guess you can say that our biologic agents are precision treatments. But what we're looking for are ways to target the right therapy to the right patient. We're not there yet, but I think when we can better characterize patients on a deep cellular and molecular level and link those characteristics to treatment responses, we will learn to target our therapies better.

Medscape: Finally, do you have any plans to get out and see San Diego?

Dr Bass: I wanted to go to Balboa Park, but honestly, I have no time!

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