A cohort study using data from the US Veterans Health Administration (VHA) found no statistically significant difference in the incidence of multiple myeloma (MM) among patients with rheumatoid arthritis (RA) treated with biologic (bDMARD) or targeted synthetic (tsDMARD) disease-modifying anti-rheumatic drugs compared to those who received only conventional synthetic (csDMARD) therapy.

The study examined whether biologic and targeted therapies might influence the risk of developing MM. Prior research has been inconclusive, and data specific to RA populations have been limited.

Researchers identified 27 540 veterans newly diagnosed with RA between 2002 and 2018. Participants were categorized based on treatment exposure: csDMARDs alone, or exposure to b/tsDMARDs, including tumor necrosis factor inhibitors (TNFi), non-TNFi biologics, and the targeted synthetic agent tofacitinib.

A Cox proportional hazards model with time-varying exposure was used to estimate the hazard ratio (HR) for developing MM, adjusting for age and other demographic factors.

Among the study cohort, 8322 veterans (30%) received a b/tsDMARD during follow-up. Over 192 000 person-years of observation, 77 incident cases of MM were identified. The age-adjusted incidence rate (IR) of MM was 0.37 per 1000 person-years among b/tsDMARD-naïve patients and 0.42 per 1000 person-years among those who had used a b/tsDMARD.

After adjusting for confounders, the hazard ratio for MM associated with b/tsDMARD use was 1.32 (95% CI, 0.78–2.26), a difference that was not statistically significant. “In this study of Veterans with RA, the rate of MM did not differ between b/tsDMARD and csDMARD users,” the authors concluded.

While this is one of the largest studies to date evaluating DMARD exposure and MM risk, the relatively small number of MM cases limits statistical power, according to the authors. Additionally, the median follow-up period of 5.8 years may not capture the long-term development of MM, which can take decades to manifest.

The authors also noted potential confounding factors related to disease severity. Patients who transitioned from csDMARDs to b/tsDMARDs may have had more severe RA, which could independently increase MM risk. The lack of detailed disease activity data at treatment initiation further limits the ability to adjust for this variable.

The study population’s demographics—predominantly male veterans—also constrain generalizability. Given the higher baseline incidence of MM among men and the smaller number of women in the VA system, sex-based comparisons were not feasible.

For managed care organizations and payers, the findings provide reassuring evidence that use of biologic or targeted synthetic DMARDs does not appear to increase MM risk in patients with RA, at least over the medium term.

However, the study underscores the need for longer follow-up and broader population studies to assess potential long-term malignancy risks associated with immunomodulatory therapy. Given the cost and widespread use of these agents, especially in chronic autoimmune conditions, continued pharmacovigilance remains essential.

Reference

Tokareva K, Peterson AC, Baraff A, et al. Use of disease modifying anti-rheumatic drugs and risk of multiple myeloma in US Veterans with rheumatoid arthritis. BMC Rheumatol. 2025;9(1):7. Published 2025 Jan 17. doi:10.1186/s41927-025-00457-3