Roy Fleischmann, MD: Efficacy of Upadacitinib and Adalimumab for Rheumatoid Arthritis

This week, Rheumatology Network sat down with Roy Fleischmann, MD, to discuss his presentations for EULAR 2021, which include topics about the side effects of JAK inhibitors, analysis of disease activity measures of methotrexate withdrawal among patients with rheumatoid arthritis, and the long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis. Fleischmann is Clinical Professor of Medicine at the University of Texas Southwestern Medical Center at Dallas and co-Medical Director of the Metroplex Clinical Research Center in Dallas.

Fleischmann delves into the well-known side effects the JAK inhibitors, including serious infections, opportunist infections, such as herpes zoster, changes in hemoglobin, and the increase in lipids. He begins by explaining that a recent report stated that tofacitinib (5 and 10 milligrams) was not as safe as TNF inhibitors, citing higher rates of malignancies and a higher hazard ratio. However, he focuses on the fact that the incident rates for both of these treatments are actually quite low and relatively comparable.

The second study compared the performance of disease activity measures for patients receiving tofacitinib after methotrexate withdrawal and those who continued with both tofacitinib and methotrexate. Investigators discovered that regardless of the disease activity state, most participants receiving tofacitinib maintained achievement of disease activity at the end of the study, regardless of methotrexate therapy. While the study was limited by the nature of being a post hoc analysis, Fleischmann believes that the results are still fairly accurate.

In his third study, Fleischmann compared 15 milligrams daily of upadacitinib plus methotrexate with adalimumab plus methotrexate. Results indicated that over 3 years, end points were in favor of upadacitinib over TNF inhibitors as far as clinical responses and patient reported outcome responses. While it was a small study in terms of safety, investigators noted a clear increased incidence of herpes zoster, liver function test abnormalities, and an increased rate of lipids with upadacitinib compared with adalimumab. However, the rates of venous thrombotic episodes were more prevalent in the adalimumab cohort.

“The companies and the FDA and the American Medical Association (AMA) are certainly very interested in this topic. And I expect that there will be many, many more analyses done on this. There is a study that is being run [that] should give us better information about the real risk. But I think that what the important point is, you don't want to minimize the risks the risks can occur,” stated Fleischmann. “This whole area is one where we still don't know what the true effects of the drugs are.”