Methotrexate in rheumatoid arthritis is frequently effective, even if re-employed after a previous failure

Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disorder of unknown aetiology that is characterized by symmetric synovitis and the propensity to cause joint destruction, disability and premature death [1-4]. Disease-modifying antirheumatic drugs (DMARDs) slow the natural course of the disease, reduce joint damage and pain, and retard loss of function and disability [5-8].However, many patients continue to have active disease despite intensive DMARD therapy, or experience adverse events [9,10]. Consequently, within 3–5 years DMARDs must be discontinued in the majority of patients [11-15]. Therefore, changes to therapeutic regimens are frequently required during the chronic course of RA, and many patients receive a large number of sequential DMARD courses [9]. In addition, more rapid switching of DMARDs has become a mainstay in the quest to prevent progression of RA if remission or at least low disease activity cannot be achieved [16,17].However, the spectrum of traditional DMARDs used in RA is limited. Although the introduction of biological agents has expanded our potential to control RA effectively [18], even these new agents have only limited efficacy in many patients [19-21], and contraindications or reimbursement issues often prevent their use. The spectrum of choices is even more limited, as it has been indicated that combinations of DMARDs are not superior to monotherapy [22,23]. Thus, many patients will reach a point at which their rheumatologists may consider the reinstitution of drugs that have already been employed in the past ('re-employment').The extent to which re-employment affects the effectiveness and tolerability of DMARDs in RA is not clear. In the present study we investigated the effectiveness and safety of re-employed DMARDs in comparison with the application of the same DMARD in earlier years, identifying patients with a history of prior DMARD failure in a large observational data set. The main focus of our analysis is on metho