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Comparative Risks of Leukopenia, Pancytopenia, Infections, Cardiovascular Events, and Malignancy with First Line Conventional Synthetic Disease-Modifying Antirheumatic Drugs (CsDMARDs) in Rheumatoid Arthritis: An International Multinational Network Cohort Study

2022; RELX Group (Netherlands); Linguagem: Inglês

10.2139/ssrn.4281766

1556-5068

James Weaver, Edward Burn, João Rafael Almeida, Loreto Carmona, Naijun Chen, Yesika Diaz Rodriguez, Talita Duarte‐Salles, Denis Granados, Meghna Jani, Seamus Kent, Raivo Kolde, Lembe Kullamaa, Jennifer C. E. Lane, K. Marinier, Henry Morgan Stewart, Carmen Olga Torre, Marta Pineda‐Moncusí, Albert Prats‐Uribe, Sulev Reisberg, Peter Rijnbeek, Ruta Sawant, Anthony G. Sena, Joel N. Swerdel, Katia Verhamme, David Vizcaya, Ross D. Williams, Cynthia Yang, Patrick Ryan, Daniel Prieto‐Alhambra,

Health Systems, Economic Evaluations, Quality of Life

Objective: We assessed the comparative risks associated with first line conventional synthetic disease modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis (RA).Methods: Routine health data from 8 databases (5 US, 1 UK, 1 Germany, and 1 Spain) informed the analysis. All databases were transformed to the OMOP common data model. New users of monotherapy csDMARD after an RA diagnosis and aged 18 or over from 2005-2019 were included in the study. Adverse events for methotrexate (MTX), hydroxychloroquine (HCQ), sulfasalazine (SSZ), and leflunomide (LEF), were assessed, with MTX the reference drug for comparisons. Cox regression after propensity score stratification was used to estimate hazard ratios (HRs) for each event according to drug use. Negative control outcomes were used to estimate calibrated HRs (cHRs) accounting for residual confounding. Findings were meta-analysed where I 2 <40%.Results: In total, 247,511 participants were included: 141,647 (57%) MTX, 73,286 (30%) HCQ, 16,521 (7%) SSZ, and 16,057 (6%) LEF. Compared to MTX, SSZ and LEF were associated with a reduced risk of any infection with pooled cHRs of 0.72 (0.57-0.90) and 0.74 (0.51-1.06). SSZ was associated with an increased risk of leukopenia (1.41, 0.91-2.18), whilst LEF was associated with reduced risks of leukopenia (0.68, 0.42-1.11) and pancytopenia (0.51, 0.24-1.07). LEF was also associated with a reduced risk of cancer (0.77, 0.53-1.11). Finally, HCQ was associated with a reduced risk of MI (0.93, 0.83-1.04) and stroke (0.88, 0.78-0.98).Conclusion: Although MTX is recommended as the first-line therapy for RA, other csDMARDs may offer specific safety benefits. Of note, SSZ and LEF were associated with approximately a 25% reduced risk of infection.