To identify risk factors of biological disease-modifying anti-rheumatic drugs (bDMARDs) initiation in patients with rheumatoid arthritis (RA).

Using the 2002–2016 Korea National Health Insurance database, we conducted a nested case-control study on seropositive RA patients. Cases (bDMARD users) and controls (users of conventional synthetic DMARDs only) were 1:4 matched on the calendar year/month of RA diagnosis and index dates (bDMARD initiation dates). Potential risk factors from two time periods, 1-year post-RA-diagnosis and 1-year pre-index, were separately assessed on the association with bDMARD initiation by conditional logistic regression analyses.

The study included 6985 cases and 27,940 controls. Older age, female gender, use of methotrexate (MTX), leflunomide, or tacrolimus as a first csDMARD, higher initial MTX dose, and initial csDMARD combination during 1-year post-diagnosis were negatively associated with later bDMARD initiation, while use of sulfasalazine as a first csDMARD, corticosteroid therapy, and higher maximal MTX dose were positively associated. Among covariates from 1-year period before bDMARD initiation, use of leflunomide, sulfasalazine, or tacrolimus, parenteral MTX, higher maximal MTX dose, corticosteroid, and csDMARD combination were positively associated with subsequent bDMARD initiation. Effects of comorbidities on bDMARD initiation were heterogenous across involved systems.

In this population-based nationwide study, we identified period-specific risk factors of bDMARD initiation among RA patients in Korea. Overall, initial aggressive RA treatment after diagnosis was associated with less use of later bDMARD, while highly intensive therapy observed just before bDMARD initiation rather reflects refractory nature of RA during this period, and did not prevent bDMARD use.