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OP0143 Methotrexate reduces immunogenicity in adalimumab treated rheumatoid arthritis patients
  1. C. Krieckaert1,
  2. M.T. Nurmohamed1,2,
  3. G. Wolbink1,3
  1. 1Rheumatology, Jan Van Breemen Research Institute, Reade
  2. 2Internal Medicine, VU Medical Center
  3. 3Sanquin Research, Amsterdam, Netherlands


Background Immunogenicity of adalimumab could impair important treatment outcomes in patients with rheumatoid arthritis (RA). Previously, we observed that patients who developed anti-adalimumab antibodies (AAA) during a three year time period achieved less often minimal disease activity or remission and more often treatment failed than in patients without AAA.[1]. In addition, we observed remarkable baseline differences between AAA positive and negative patients, including the use and dose of methotrexate.

Objectives To examine whether the use and dose of concomitant methotrexate influenced the development of AAA.

Methods Patients of the adalimumab cohort (n=272) at the Jan van Breemen Research Institute | Reade, were stratified according to the baseline methotrexate dose: no concomitant methotrexate (n=70), low (5-10 mg/wk, n=40), intermediate (12.5-20 mg/wk, n=54), or high dose methotrexate (>22.5 mg/wk, n=108). Percentages of patients developing AAA per methotrexate dose group were calculated and compared over time using General Estimation Equations (GEE).

Results In figure 1 the percentages of patients developing AAA per methotrexate dose group during follow-up are shown. The statistical GEE model revealed that patients using methotrexate developed AAA less often compared to patients without methotrexate: low dose vs. no methotrexate OR 0.36 (95%CI 0.18-0.74); intermediate dose vs. no methotrexate OR 0.22 (95%CI 0.10-0.46); high dose vs. no methotrexate OR 0.14 (95%CI 0.07-0.28). Additional odds ratios for intermediate vs. low dose were 0.60 (95%CI 0.25-1.44), 0.39 (95%CI 0.17-0.88) for high vs. low dose, and 0.65 (95%CI 0.28-1.50) for high vs. intermediate dose.

Conclusions Methotrexate abolishes immunogenicity in a dose-dependent manner.This has implications for other biological therapeutics and inflammatory diseases in which concomitant methotrexate administration is less common. Altogether, the immune-tolerating ability of methotrexate as well as assessment of the optimal dose should be investigated further and the results of our present study are promising for the optimization of treatment responses and easy applicable in clinical practice.

  • [1] Bartelds et al. JAMA 2011;305(14):1460-8.

Disclosure of Interest C. Krieckaert: None Declared, M. Nurmohamed Grant/Research support from: Abbott, Roche, Pfizer, Consultant for: Abbott, Roche, MSD, UCP, SOBI, BMS, Speakers Bureau: Abbott, Roche, Pfizer, G. Wolbink Grant/Research support from: Pfizer, Speakers Bureau: Pfizer, Amgen

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