In a study reported in JAMA Network Open, Sendaydiego et al identified the risks associated with use of disease-modifying antirheumatic drugs (DMARDs) in U.S. patients with rheumatoid arthritis. As noted by the investigators, a previous study has shown increased risk of cancer with use of tofacitinib vs tumor necrosis factor (TNF) inhibitors.
Study Details
The retrospective cohort study used claims from Merative Marketscan Research Databases from November 2012 to December 2021, with follow-up occurring for up to 2 years after initiation of biologic or targeted synthetic DMARDs. The analysis included new initiations of TNF inhibitors, abatacept, interleukin 6 (IL-6) inhibitors, rituximab, and JAK inhibitors.
The primary outcome measure was incident cancer (excluding nonmelanoma skin cancer) after at least 90 days and within 2 years of initiation of biologic or targeted synthetic DMARDs. Among patients who had multiple exposures, outcomes were associated with the most recent exposure.
Key Findings
Among the total of 27,661 drug exposures included in the analysis, there were 20,586 TNF inhibitor exposures (74%), 2,570 JAK inhibitor exposures (9%), 2,255 abatacept exposures (8%), 1,182 rituximab exposures (4%), and 1,068 IL-6 inhibitor exposures (4%).
On crude analysis, cancers were observed in 0.8%, 1.2%, 0.8%, 1.3%, and 0.9% of patients receiving TNF inhibitors, rituximab, IL-6 inhibitors, abatacept, and JAK inhibitors, respectively.
On multivariate analysis, risk of cancer compared with use of TNF inhibitors was significantly increased with use of rituximab (hazard ratio [HR] = 1.91, 95% CI [confidence interval] = 1.17–3.14) and abatacept (HR = 1.47, 95% CI = 1.03–2.11) and numerically increased with use of JAK inhibitors (HR = 1.36, 95% CI = 0.94–1.96); the HR for use of IL-6 inhibitors was 1.04 (95% CI = 0.57–1.92).
The investigators concluded: “In this cohort study of individuals with [rheumatoid arthritis] and new biologic or targeted synthetic DMARD exposures, individuals initiating rituximab, abatacept, and JAK [inhibitors] demonstrated higher incidence rates and statistically significantly increased risks of incident cancers compared with those initiating TNF [inhibitors] in the first 2 years after initiation of biologic or targeted synthetic DMARDs. Given the limitations of administrative claims data and confounding by indication, it is likely that these patients may have a higher disease burden, resulting in channeling bias. To better understand these associations, larger studies with longer follow-up time are needed.”
Namrata Singh, MD, MSCI, of the University of Washington, Seattle, is the corresponding author for the JAMA Network Open article.
Disclosure: The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging of the National Institutes of Health. For full disclosures of the study authors, visit www.jamanetwork.com.
