THU0130 Assessment of transaminasitis with daily methotrexate therapy in patients with inflammatory rheumatic diseases. A long-term follow-up cohort study

Background Methotrexate (MTX) is the most commonly used DMARD in the treatment of rheumatoid arthritis and other rheumatic diseases. MTX is often administered weekly (WMTX), because the drug has been considered more hepatototoxic when taking daily. A randomized clinical trial reported that nausea, vomiting, headache are less common side effects with daily MTX (DMTX). 1 We reported a comparative study of 180 patients which highlights the same or lower rate of transaminasitis in patients under DMTX than WMTX. 2 Objectives To determine the rate of hepatotoxicity of DMTX in a cohort with a large follow-up. Methods A retrospective study was performed of our patients treated with methotrexate in daily doses (DMTX) (our patients have been treated under DMTX for more than 20 years of medical practice). We describe the demographic factors including age, sex, diseases in which MTX is administrated, time of evolution of the disease; we compared patients with transaminasitis and patients without transaminasitis for describing factors associated with this event. ALT/AST levels were evaluated in our patients every 3 months. Results We included 875 patients with 2.6±3.6 years of treatment with methotrexate, 10 patients were under MTX treatment up to 20 years; 534 patients have rheumatoid arthritis (RA), 93 systemic lupus erythematosus (SLE), and 248 other rheumatic diseases. Sixty four patients were less than 18 year-old, and 91 over 65. Only 56/875 (6.4%) had transaminasitis (more than two-fold the normal level of ALT/AST), 18 patients had 2 or more episodes of transaminasitis, moreover, only 20 patients had 3-fold elevation of AST/ALT. Table 1 shows the main characteristics of the patients included in our study. Only alcoholism and higher body mass index (BMI) were statistically significant factors associated with transaminasitis. Conclusions Our study describes the security of daily dosage of MTX (liver toxicity) in a large follow-up. This study justifies a randomized clinical trial, to evaluate security and to confirm better profile of adverse events with DMTX than WMTX doses. The clinician must discard the association of alcohol and fatty liver disease in patients with transaminasitis and the use of MTX. References Radmanesh M, Rafiei B, Moosavi ZB, Sina N. Weekly vs. daily administration of oral methotrexate (MTX) for generalized plaque psoriasis: a randomized controlled clinical trial. Int J Dermatol. 2011;50:1291-3. Moreno-Valdes R, Martinez-Martinez MU, Cuevas-Orta E, et al. Methotrexate Every Day Is Safe and Effective As Weekly Dosage. Arthritis Rheum 2011; Suppl 63:S881 (abstract 2251). Disclosure of Interest None Declared