Jeffrey Curtis, MD, MS, MPH: Malignancies in Patients with Rheumatoid Arthritis and Cardiovascular Risk

Rheumatology Network interviewed Jeffrey Curtis, MD, MS, MPH, to discuss his ACR Convergence presentation entitled, “Malignancies in Patients Aged ≥ 50 Years with RA and ≥ 1 Additional Cardiovascular Risk Factor: Results from a Phase 3b/4 Randomized Safety Study of Tofacitinib vs TNF Inhibitors.” Curtis is Professor of Medicine in the Division of Clinical Immunology and Rheumatology at the University of Alabama at Birmingham. He explains the ORAL Surveillance study design, the most common malignancies observed in patients with rheumatoid arthritis, and the clinical significance of these results.

Highlights of our conversation include:

Rheumatology Network: What initially sparked your interest in analyzing malignancies in patients with rheumatoid arthritis who received tofacitinib?

Jeffrey Curtis, MD, MS, MPH: There's a tremendous interest in understanding the safety profile of Janus kinase inhibitors, or JAK inhibitors, in relation to other therapies like tumor necrosis factor (TNF) inhibitors or other biologic drugs in patients with rheumatoid arthritis. This topic has been rather controversial and a source of a lot of intense regulatory agency interests, given the safety profile of JAK inhibitors versus TNF inhibitors, resulting from the large industry-sponsored safety study that recently read out earlier this year.

RN: What were the most common malignancies you observed in patients with rheumatoid arthritis?

JC: The most common malignancies that we observed were both lung cancer and breast cancer. And those, frankly, are common malignancies that we see in patients with rheumatoid arthritis (RA) in general. So, there wasn't anything terribly unexpected or untoward with respect to the kinds of malignancies that are common. Lymphomas, of course, are always high on people's radar. And in patients with RA, with the immune system effects on that kind of hematologic malignancy, it was lung and breast cancer that accounted for the majority of them.

RN: Why do you believe malignancies were higher in patients receiving tofacitinib?

JC: There's a lot of speculation about whether the mechanism of action or other factors about what tofacitinib does or how JAK inhibitors work and affect the immune system. The immune system, of course, was responsible for immune surveillance, including protecting us against malignancies and our own cancer cell transformation. The short answer is that you can posit a whole number of biologic mechanisms for causality but results from this large safety study nevertheless yielded the results that they did. That said, there were some interesting subgroup analyses. In lower risk people, people who weren't over age 65 and those who had never smoked, there was no increase in risk. It appeared that the risk was confined to older people over age 65 and those with a history of smoking. There be some Interplay there with a history of tobacco use. So, as that's post hoc, you have to take that with something of a grain of salt. But it looked like in sort of the average risk patient or even lower risk patients, there really wasn't a difference. It was only older people and those who were smokers that had the vast majority of this excess risk.