Use of disease modifying anti-rheumatic drugs and risk of multiple myeloma in US Veterans with rheumatoid arthritis

使用改善病情抗风湿药物与美国患有类风湿性关节炎的退伍军人罹患多发性骨髓瘤的风险

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Abstract

BACKGROUND: Biologic (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) used in the management of rheumatoid arthritis (RA) target inflammatory pathways implicated in the pathogenesis of multiple myeloma (MM). It is unknown whether use of b/tsDMARDs affects the incidence of MM. METHODS: In this cohort study using Veterans Health Administration (VHA) data, we identified Veterans newly diagnosed with RA from 1/1/2002 to 12/31/2018 using diagnostic codes and medication fills. DMARD exposure was categorized as follows: conventional synthetic (cs)DMARDs; bDMARDs, which included tumor necrosis factor inhibitors (TNFi), non-TNFi; and a tsDMARD, tofacitinib. A Cox proportional hazards model with time-varying exposure was used to estimate the hazard ratio for developing MM among those who received b/tsDMARD medications relative to b/tsDMARD-naïve persons. RESULTS: 27,540 veterans with RA met eligibility criteria of whom 8322 (30%) took a b/tsDMARD during follow-up. There were 77 incident cases of MM over 192,000 person-years of follow-up. The age-adjusted incidence rate (IR) of MM among b/tsDMARD-naïve patients was 0.37 (95% CI 0.28-0.49) per 1000 person-years and 0.42 among current or former b/tsDMARD users (95% CI 0.25-0.65). Adjusting for age and other demographic characteristics, the hazard ratio for MM associated with use of b/tsDMARDs was 1.32 (95% CI 0.78, 2.26). CONCLUSION: In this study of Veterans with RA, the rate of MM did not differ between b/tsDMARD and csDMARD users. The relatively short duration of follow-up and few events limited our power to detect treatment-related differences in MM risk.

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