LAUSR

Background Methotrexate inhibits the metabolism of purines resulting in the accumulation of adenosine; it also inhibits the activation of T cells and suppresses the expression of intercellular adhesion molecules for T cells. Side effects may show up during the treatment and among them there is hepatic toxicity, characterised by an increase of AST and ALT; such increase is usually asymptomatic but it may lead to a suspension of the treatment. Metadoxine (MTDX) is a drug which is used in order to treat both acute and chronic alcohol intoxication; it also prevents the inactivation of ATP from acetaldehyde and pyroglutamic acid. MTDX also showed to improve hepatic function markers and to decrease oxidative stress leading to a protective effect against radicals. Objectives The aim of this preliminary study was to evaluate the possible effect of MTDX on hepatic function in patients affected by RA in therapy with MTX. Methods The study involved the recruitment of patients affected by RA in treatment with MTX; a following random selection of a subgroup of patients who took MTDX (500 mg twice a day for 28 days, from the 5th to the 8th week of therapy with MTX) was performed. All the patients underwent a 12-week-follow up in which these parameters were evaluated: demographics, blood tests required for MTX in accordance with datasheets (especially AST and ALT), CRP, ESR, ACPA, numbers of swollen and tender joints, concomitant medications (NSAIDs and steroids) and the degree of disability (HAQ, table 1). Results 24 patients affected by RA (20 women), with an mean age of 51.3 years (±14.1) and mean MTX dose of 12.3±2.6, were recruited. 70.3% took GC with a medium dosage (3.72±2.71). Among these 24, 13 patients were underwent MDTX 500 mg twice a day from the 5th to the 8th week. Patients treated with MTDX+MTX showed a significant decrease of hepatic markers (AST Δ−18.38 p=0.004 – ALT Δ−19.23 p=0.004) compare with patients with MTX only (AST Δ−4.27 p=0.110 – ALT Δ−6.09 p=0.045) after a 12-week-monitoring, with no statistically significant difference concerning disease activity (table 2).Abstract AB0499 – Table 1 Variables at baseline SD: standard deviation; ns: not significant; AST: aspartate amino transaminase; ALT: alanine amino transaminase; MTX: methotrexate; MTDX: Metadoxine; GC: glucocorticoidsAbstract AB0499 – Table 2 Comparison of Hepatic Functions between two groups AST: aspartate amino transferase; ALT: alanine amino transferase; MTX: Methotrexate; MTDX: Metadoxine; Conclusions This study showed the possible effect of MTDX in increasing the tolerance to the MTX without affecting its effectiveness. Its role may indeed have useful implications in patients who start the therapy with MTX or in those who develop hepatic toxicity during the treatment. Reference [1] Fehér J, et al. The Beneficial Effect of Metadoxine in the Treatment of Fatty Liver Diseases. Reviews2009;3(1):65–79. Disclosure of Interest None declared