RT Journal Article
SR Electronic
T1 Safety of the Methotrexate–leflunomide Combination in Rheumatoid Arthritis: Results of a Multicentric, Registry-based, Cohort Study (BiobadaBrasil)
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.201248
DO 10.3899/jrheum.201248
A1 Markus Bredemeier
A1 Roberto Ranza
A1 Adriana M.  Kakehasi
A1 Aline Ranzolin
A1 Inês G.  da Silveira
A1 Ana C.M.  Ribeiro
A1 David C.  Titton
A1 André L.S.  Hayata
A1 Hellen M.S.  Carvalho
A1 Bárbara S.  Kahlow
A1 Vander Fernandes
A1 Paulo  Louzada Jr
A1 Manoel B.  Bértolo
A1 Ângela L.B.P.  Duarte
A1 José C.  Macieira
A1 José R.S.  Miranda
A1 Geraldo R.C.  Pinheiro
A1 Reginaldo B.  Teodoro
A1 Marcelo M.  Pinheiro
A1 Valéria Valim
A1 Ivânio A.  Pereira
A1 Maria F.L.C.  Sauma
A1 Gláucio R.W.  de Castro
A1 Laurindo F.  da Rocha Jr
A1 Sâmia A.S.  Studart
A1 Morgana O.  Gazzeta
A1 Leticia G.  da Silveira
A1 Cristiano M.  Lupo
A1 Ieda M.M.  Laurindo
YR 2021
UL http://www.jrheum.org/content/early/2021/07/11/jrheum.201248.abstract
AB Objective To evaluate the safety of the methotrexate (MTX)–leflunomide (LEF) combination in rheumatoid arthritis (RA), comparing it with other therapeutic schemes involving conventional synthetic (cs-) and biologic (b-) disease-modifying antirheumatic drugs (DMARDs) or Janus kinase inhibitors ( JAKi). Methods Patients with RA starting a treatment course with a csDMARD (without previous use of bDMARD or JAKi) or their first bDMARD/JAKi were followed up in a registry-based, multicentric cohort study in Brazil (BiobadaBrasil). The primary outcome was the incidence of serious adverse events (SAEs); secondary outcomes included serious infections. Multivariate Cox proportional hazards models and propensity score matching analysis (PSMA) were used for statistical comparisons. Results In total, 1671 patients (5349 patient-years [PY]) were enrolled; 452 patients (1537 PY) received MTX + LEF. The overall incidence of SAEs was 5.6 per 100 PY. The hazard of SAEs for MTX + LEF was not higher than for MTX or LEF (adjusted HR [aHR] 1.00, 95% CI 0.76–1.31, P = 0.98). MTX + LEF presented a lower hazard of SAEs (aHR 0.56, 95% CI 0.36–0.88, P = 0.01) and infectious SAEs (aHR 0.48, 95% CI 0.25–0.94, P = 0.03) than bDMARDs/JAKi with MTX or LEF. MTX + LEF presented lower hazard of SAEs than MTX + sulfasalazine (SSZ; aHR 0.33, 95% CI 0.16–0.65, P = 0.002). Analysis using PSMA confirmed the results obtained with traditional multivariate Cox analysis. Conclusion In our study, MTX + LEF presented a relatively good overall safety profile in comparison to MTX + SSZ and schemes involving advanced therapies in RA.