Leflunomide discontinuation in rheumatoid arthritis and influence of associated disease-modifying anti-rheumatic drugs: a survival analysis L Rodriguez-Rodriguez, JA Jover-Jover, O Fontsere, RC Peña-Blanco, L León, B Fernández-Gutierrez, L Abásolo Department of Rheumatology and Health Research Institute, San Carlos Clinical Hospital (IDISSC), Madrid, Spain Objectives: The aims of this study were to describe the rate of leflunomide discontinuation in rheumatoid arthritis (RA) patients, in standard clinical practice, and to analyse which factors could influence this rate, paying particular attention to the concomitant treatment with other disease-modifying anti-rheumatic drugs (DMARDs). Method: We selected RA patients, diagnosed according to the 1987 American College of Rheumatology (ACR) criteria, attending the rheumatology outpatient clinic of the San Carlos Clinical Hospital (Madrid, Spain), who had started treatment with leflunomide between 1 January 2006 and 1 January 2011. Clinical records were examined until withdrawal of the drug, loss of follow-up, or 1 October 2011. Kaplan–Meier curves were set to account for leflunomide withdrawal. Cox bivariate and multivariate regression models were conducted to examine risk factors for leflunomide discontinuation. Results: The incident rate (IR) for leflunomide discontinuation, regardless of the cause, was 27 per 100 patient-years [95% confidence interval (CI) 22–31]. We observed, in both the bivariate and multivariate regression analysis, that those aged > 75 years at the start of the leflunomide treatment and undergoing concurrent treatment with methotrexate (MTX) and/or hydroxychloroquine (HC) had a significantly higher risk of leflunomide discontinuation. Conclusions: An older age at the start of the treatment with leflunomide, or concomitant treatment with MTX and/or HC, could be associated with a higher risk of leflunomide discontinuation, regardless of the cause. Therefore, when taking MTX or HC, patients receiving leflunomide should be closely monitored early to detect the occurrence of adverse reactions, and hence prevent their aggravation. Rheumatoid arthritis (RA) is an autoimmune disease associated with increased morbidity and mortality (1). The full benefit of the immunosuppressive drugs used to induce or maintain disease remission requires compliance with the treatment regimens. Non-adherence to and dis- continuation of pharmacological therapies are important contributors to delayed recovery, accelerated progression of disease, and the need for more aggressive treatment (2). Leflunomide is an isoxazole derivative specifically developed as a disease-modifying anti-rheumatic drug (DMARD) for the treatment of RA. In randomized con- trolled trials, this drug showed a similar efficacy, tolerability, and discontinuation rates when compared to methotrexate (MTX) and sulfasalazine, up to 2 years of follow-up (3, 4). However, it is important to take into account that the trial settings are different from day-to-day clinical practice, which limits the validity of the extrapolated data to patients in daily practice (5). To inform about those potential dis- crepancies, observational studies have been performed in recent years (6–13). However, most of these studies fol- lowed the patients for up to about 2 years, were conducted soon after the drug was approved for use, and factors asso- ciated with drug withdrawal were not studied. The aims of our current study were to describe the rate of leflunomide discontinuation in RA patients who were attending our rheumatology outpatient clinic, and to ana- lyse which factors could influence this rate, paying parti- cular attention to concomitant treatment with other DMARDs. Method Study design We carried out a retrospective longitudinal study of 4 years of follow-up, in accordance with the Declaration of Helsinki and approved by the San Carlos Clinical Hospital (Madrid, Spain) Ethics Committee. Patients We selected all patients who fulfilled the 1987 American College of Rheumatology (ACR) classification criteria Luis Rodriguez-Rodriguez, Department of Rheumatology, San Carlos Clinical Hospital, c/ Professor Martín Lagos, s/n, Madrid 28040, Spain. E-mail: lrodriguezr.hcsc@salud.madrid.org Accepted 11 March 2013 Scand J Rheumatol 2013;42:433–436 433 © 2013 Informa Healthcare on license from Scandinavian Rheumatology Research Foundation DOI: 10.3109/03009742.2013.785590 www.scandjrheumatol.dk