AB0375 The effect of concomitant use of methotrexate on the clinical activity in patients with rheumatoid arthritis under ANTI-TNFTHERAPY
Authors: A Martinez-Feito, C Plasencia, B Hernandez-Breijo, A Jochems, C Diego, A Villalba, D Peiteado, L Nuño, P Nozal, A Balsa, D Pascual-Salcedo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Several publications in rheumatoid arthritis (RA) have demonstrated a beneficial effect of concomitant methotrexate (MTX) use with TNF inhibitors (TNFi), mainly because of the MTX effect in reducing immunogenicity. In a previous work in the RA-La Paz cohort, we found that the concomitant use of MTX had a positive effect on the pharmacokinetics of serum TNFi levels, decreasing the immunogenicity of these drugs. Furthermore, the MTX effect was dose-dependent, being greater at high MTX dose. Currently, we investigate the effect of concomitant MTX use on the clinical response. <h3>Objectives</h3> To investigate the MTX influence on the clinical response in the RA-La Paz cohort treated with Infliximab (Ifx), Adalimumab (Ada) or Etanercept (Etn) at one year of treatment. <h3>Methods</h3> This is an observational study from a prospective cohort from the Biological Unit of the University Hospital La Paz, Madrid, Spain that analysed a total of 293 RA patients treated with Ifx (112 patients), Ada (71 patients) and Etn (110 patients). Patients were grouped according to the MTX dose: no MTX, low dose (LD: ≤12.5 mg/week), intermediate dose (ID: 15–17.5 mg/week) and high dose (HD: ≥20 mg/week). For this study, the clinical response was evaluated by DAS28-ESR and the clinical improvement byΔDAS28. Data were collected at baseline, 0.5 and 1 year of TNFi treatment. Statistical analysis was performed using GraphPad Prism 6.0 software. <h3>Results</h3> Out of 293 RA patients (pts) under TNFi treatment, 184 (71 with Ifx, 40 with Ada and 73 with Etn) were included. In this cohort, 128 (70%) pts used concomitantly MTX (91% oral administration) and 56 (30%) pts were in monotherapy. No differences in DAS28 were found at baseline between patients with or without MTX (p=0.8). After one year of treatment, pts with TNFi +MTX have a significantly lower DAS28 than patients without MTX (3.3±1.3 vs 3.9±1.1; p=0.004). When analyzing the DAS28 values in relationship to the MTX dose, statistical differences are observed with use of HD (≥20 mg/week) (3.1±1.3 with HD vs 3.9±1.1 without MTX; p=0.001) but not with intermediate (3.4±1.2 with ID vs3.9±1.1 without MTX; p=0.06) or low MTX dose (3.8±1.6 with LD vs 3.9±1.1 without MTX; p=0.4) at 1 year of therapy. Clinical improvement byΔDAS28 was higher in patients with TNFi +MTX than in patients without MTX (1.7±1.4 vs 1±1.3p=0.007). This effect was observed with all MTX doses (1.7±1.5 with HD vs 1±1.3 without MTX, p=0.01; 1.6±1.3 vs with ID 1±1.3without MTX, p=0.03; 1.8±1.3 with LD vs 1±1.3 without MTX, p=0.01). <h3>Conclusions</h3> In the RA-La Paz cohort under TNFi treatment, the concomitant use of MTX has a positive effect on the clinical activity, mainly when high dose of MTX is used. Moreover, we demonstrate a positive effect of any MTX dose on the clinical improvement at one year of treatment. <h3>Disclosure of Interest</h3> None declared