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AB0375 The effect of concomitant use of methotrexate on the clinical activity in patients with rheumatoid arthritis under ANTI-TNFTHERAPY
  1. A Martinez-Feito1,
  2. C Plasencia2,
  3. B Hernandez-Breijo1,
  4. A Jochems1,
  5. C Diego3,
  6. A Villalba2,
  7. D Peiteado2,
  8. L Nuño2,
  9. P Nozal3,
  10. A Balsa2,
  11. D Pascual-Salcedo1
  1. 1Immuno-Rheumatology research group
  2. 2Rheumatology
  3. 3Immunology, University Hospital la Paz, madrid, Spain

Abstract

Background 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.

Objectives 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.

Methods 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.

Results 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).

Conclusions 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.

Disclosure of Interest None declared

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