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Optimalisation of the clinical pharmacogenetic model to predict methotrexate treatment response: the influence of the number of haplotypes of MTHFR 1298A–677C alleles on probability to respond
  1. W M Kooloos1,
  2. J A M Wessels1,
  3. S M van der Kooij2,
  4. C F Allaart2,
  5. T W J Huizinga2,
  6. H-J Guchelaar1
  1. 1
    Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2
    Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  1. W M Kooloos, Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, PO Box 9600, NL 2300 RC Leiden, The Netherlands; w.m.kooloos{at}

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Several single nucleotide polymorphisms (SNP) have been reported to be associated with the efficacy of methotrexate in the treatment of rheumatoid arthritis (RA).1 2 Subsequently, we developed a clinical model to predict the efficacy of methotrexate monotherapy in patients with recent-onset RA (N  =  205).3 The model consists of non-genetic factors, sex, rheumatoid factor and smoking status, disease activity score (DAS) before starting methotrexate and four genetic polymorphisms (MTHFD1 1958G>A, AMPD1 34C>T, ITPA 94A>C and ATIC 347C>G). Associations of these factors with the response to methotrexate were transformed into a scoring system ranging from 0 to 11.5 points. The predictive model showed a positive predictive value of 95% and a negative predictive value of 86% and was able to categorise 60% of …

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  • Competing interests: None.

  • Funding: The Foundation Nuts Ohra (Amsterdam) and Schering-Plough BV contributed to this work financially.

  • Ethics approval: Ethics approval was obtained from Leiden University Medical Centre, Leiden, The Netherlands.

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