Background/Purpose: Epidemiologic studies suggest that disease duration and degree of inflammatory activity of rheumatoid arthritis (RA) are associated with lymphoma development [1]. Whether the decrease in inflammatory burden seen with use of biologic or targeted synthetic disease modifying antirheumatic drugs (bDMARDs or tsDMARDs) translates into a lower risk of lymphoma in RA needs to be assessed.

Methods: We identified patients >18 years of age diagnosed with RA in any US Veterans Affairs (VA) facility from 1/1/2002 and 12/31/2018 using the VA Corporate Data Warehouse (CDW). To be included, each patient was required to meet the following criteria: 2+ RA diagnostic codes at least 7 days apart but no more than 365 days apart; 2) a prescription for a conventional synthetic DMARD (csDMARD) within 90 days of the first RA diagnosis; and 3) an inpatient or outpatient visit 30 days to 2 years preceding first RA diagnosis (indicating they are a regular user of the VA). The csDMARDs included in these analyses were: methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine. The bDMARDs included were tumor necrosis factor inhibitors (TNFi) and non-TNFi biologics such as tocilizumab, rituximab, abatacept, and biosimilars; tsDMARD was tofacitinib. Patients with prevalent lymphoma were excluded. Lymphoma diagnoses were identified using International Classification of Diseases Version 9, 10 and Oncology (ICD9, ICD10, ICDO) codes. We used marginal structural models as described by Hernan et al [2] to control for confounding by indication while evaluating this association. We adjusted for baseline demographics (age, sex, race, ethnicity, year of cohort entry, rheumatology visits), and time-varying CRP, ESR, Rheumatoid Disease Comorbidity Index (RDCI) [3], use of non-steroidal anti-inflammatory drugs and opioids to control for confounding.

Results: 27,421 Veterans with RA met our eligibility criteria, of whom 8,225 (30%) were treated with a b-/tsDMARD at some point. The crude incidence rates were 1.71 (95% CI 1.5-1.94) per 1000 person-years for those only on csDMARDs and 1.78 (95% CI 1.44-2.18) for patients during or following use of a b/tsDMARDs. After adjustment with both time-fixed and time-varying covariates, the incidence of lymphoma was not different between patients who did and did not use a b/tsDMARD (hazard ratio=1.04, 95% CI= 0.80-1.35).

Conclusion: In this large study using the nationwide VA data, we did not observe an association between the use of b/ts DMARDs and an altered risk of lymphoma.

References:
1. Baecklund E, Iliadou A, Askling J, Ekbom A, Backlin C, Granath F, Catrina AI, Rosenquist R, Feltelius N, Sundstrom C et al: Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 2006, 54(3):692-701.
2. Hernan MA, Brumback B, Robins JM: Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. Epidemiology 2000, 11(5):561-570.
3. England BR, Sayles H, Mikuls TR, Johnson DS, Michaud K: Validation of the rheumatic disease comorbidity index. Arthritis care & research 2015, 67(6):865-872.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/use-of-biologic-or-targeted-synthetic-disease-modifying-anti-rheumatic-drugs-and-the-risk-of-lymphoma-in-rheumatoid-arthritis/