Targets of biologic disease‐modifying antirheumatic drugs and risk of multiple myeloma. Issue 5 (8th February 2020) - Calip, Gregory S.
Abstract : Several commonly used immune‐suppressing biologic drugs target proteins and cytokines involved in myeloma pathogenesis. Our objective was to determine whether targeted biologic disease‐modifying antirheumatic drugs (DMARDs) are associated with risk of multiple myeloma (MM). We conducted a nested case–control study within a retrospective cohort of 56, 886 commercially insured adults undergoing treatment for rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis between 2009 and 2015 using the Truven Health MarketScan Databases. MM cases ( n = 287) were matched to up to 10 controls ( n = 2, 760) on age, sex and rheumatologic indication using incidence density sampling without replacement. Our exposures of interest were biologic DMARDs targeting tumor necrosis factor‐alpha, interleukin 6, cytotoxic t‐lymphocyte‐associated protein‐4 and depletion of B cells. Relative risks were estimated as adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression models. Cases and controls were similar with respect to use of prescription NSAIDs and concurrent conventional‐synthetic DMARDs. Cases had slightly fewer etanercept users (4% vs . 7%) and slightly more tocilizumab users (1.4% vs . 0.4%). Compared to patients treated with only conventional‐synthetic DMARDs, those receiving concomitant conventional‐synthetic plus biologic DMARDs had lower risk of developing MM (OR = 0.48; 95% CI 0.30–0.88; p = 0.02). Risks differed by drug target with an inverse association observed with use of etanercept inhibiting tumor necrosis factor‐alpha (OR = 0.55; 95% CI 0.30–1.02; p = 0.06) and a positive association with tocilizumab inhibiting interleukin‐6 (OR = 4.33; 95% CI 1.33–14.19; p = 0.02) compared to biologic DMARD‐naïve patients. Further investigation is warranted to understand the roles of drugs suppressing tumor necrosis factor‐alpha and interleukin‐6 in myeloma pathogenesis. Abstract : What's new? Biologic disease‐modifying antirheumatic drugs (DMARDs) reduce inflammation and slow the progression of rheumatoid arthritis and other autoimmune conditions. In exerting these effects, DMARDs target proteins that are associated with the pathogenesis of multiple myeloma (MM). This retrospective cohort study shows that, compared to conventional synthetic DMARDs only, concomitant use of synthetic and biologic DMARDs is inversely associated with MM risk. However, observed associations differed by drug targets. Namely, the biologic DMARD etanercept, which inhibits tumor necrosis factor‐alpha, was inversely associated with MM, while tocilizumab, which blocks interleukin‐6, was positively associated with MM. Possible roles for these targets in MM therapy warrants further investigation.