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FRI0168 Effect of Methotrexate in The Presence of Drug and The Appearance of Antibodies against TNF Inhibitors in Patients with Rheumatoid Arthritis
  1. A. Martínez-Feito1,
  2. C. Plasencia2,
  3. A. Villalba2,
  4. T. Jurado1,
  5. A. Mezcua1,
  6. E. Martín-Mola2,
  7. G. Bonilla2,
  8. A. Balsa2,
  9. D. Pascual-Salcedo1
  1. 1Department of Immunology
  2. 2Department of Rheumatology, Hospital Universitario de La Paz, Madrid, Spain

Abstract

Background Several factors influence pharmacokinetics of TNFinhibitors (TNFi). One relevant factor is the formation of anti drug- antibodies (ADA) associated with low drug levels and a worse clinical response. Recent publications in rheumatoid arthritis (RA) 1,2 have demonstrated a beneficial effect of concomitant use of anti-TNF drugs and methotrexate (MTX), with a dose-dependent effect.

Objectives To analyze the MTX influence on the presence of drug and appearance of ADA in a cohort of RA patients treated with Infliximab (Ifx), Adalimumab (Ada) or Etanercept (Etn) with a long follow-up (3 years).

Methods This is a retrospective study that analyzed patients with RA treated with Ifx (112 patients), Ada (71 patients) and Etn (110 patients), in a prospective observational biological cohort from the University Hospital La Paz, Madrid, Spain. Patients were grouped according to the use of MTX: no MTX, low dose (≤12.5 mg/week), intermediate dose (12.5–20 mg/week) and high dose (≥20 mg/week). Levels of drug and ADA were measured by capture and bridging ELISA respectively at baseline, 0.5, 1, 2 and 3 years. All samples were obtained just before drug administration. Statistical analysis was performed using GraphPad Prism 5.0 software.

Results Out of 293 RA patients with a TNFi treatment; 184 (71 with Ifx, 40 with Ada and 73 with Etn) were included. In this cohort, 111 (61%) were on MTX and 72 (39%) were on monotherapy. Most patients with high dose of MTX had levels of drug over 3 years of treatment (93% with MTX ≥20 mg/week vs 77% without MTX; p=0.01) being significant since 0.5 years (≥60% with MTX 20 mg/week vs 39% without MTX; p=0.02)

To analyze the ADA development, patients treated with Ifx and Ada were grouped and we observed a trend to a higher percentage of ADA in the group which did not receive MTX (n=37) compared to those who received high-dose MTX (n=27) although not statistically significant (32% vs 19%, p=0.21). Analysing by separate drugs MTX significantly reduced the immunogenicity of Ada, (53% in patients with MTX vs 15% in monotherapy; p=0.02).

When we study the lack of circulating drug (Ifx, Ada and Etn) as an indicator of immunogenicity, patients who did not receive MTX (n=56) had higher absence of drug than patients with high-dose MTX (n=61) (34% vs 10%, respectively; p<0.01). This effect was significant since 0.5 years of treatment (16% MTX ≥20 mg/week vs 3% without MTX; p=0.017)

Conclusions In our cohort of RA patients the concomitant use of MTX has a positive effect in the persistence of TNFi levels together with a decrease of immunogenicity. Furthermore, the MTX has a dose-dependent effect being greater at high dose of MTX.

  1. Krickaert C et al.ARD 2012; 71:11.

  2. Vogelzang E H et al.ARD 2015; 74:2

Acknowledgement This work is partially funded by a non restricted grant from Pfizer

Disclosure of Interest None declared

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