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FRI0016 Factors predicting methotrexate dose and effectivity
  1. M Hoekstra1,
  2. A Van Ede2,
  3. C Haagsma1,
  4. M Van de Laar1,
  5. R Laan2
  1. 1Department of Rheumatology, Medisch Spectrum Twente, Enschede, The Netherlands
  2. 2Department of Rheumatology, University Hospital St Radboud, Nijmegen, The Netherlands


Background Methotrexate is the most effective treatment in rheumatoid arthritis. Dose and clinical effect are related.

Objectives To determine predictive factors for reaching a dose of > 12.5 mg/week and effectivity.

Methods Data from a double-blind placebo controlled multicenter study on patients with active rheumatoid arthritis were used. In this trial the effect of folic acid (1‑2 mg/day), folinic acid (2.5 mg/week) and placebo along methotrexate therapy (7.5-maximum 25 mg/week) was compared. The patients never had methotrexate before, had active disease and a creatinine clearance >50 ml/min. The three groups contained 133, 141 and 137 patients respectively. The follow-up was 48 weeks.

By means of multiple stepwise regression analysis we studied the relation between baseline variables and the following: methotrexate dose > 12.5 mg/week and effectivity (lowest DAS1.08).

Results Effectivity:

We found no significant relation between baseline characteristics and effectivity.

When we only look at a change in DAS >1.08 the disease duration (months) is significantly associated (p = 0.035)

(P = 0.678 + 0.0015 disease duration)

Methotrexate dose > 12.5 mg/week:

Reaching a dose > 12.5 mg/week is significantly associated with folate suppletion (p < 0.0001) and negatively with gastro-intestinal history, e.g. peptic ulcers and abdominal surgery (p = 0.037).

(P = 0.678–0.292 no folate – 0.013GI-history)

Conclusion Baseline characteristics do not predict effectivity. A positive gastro-intestinal history had a small negative effect on methotrexate dose. Reaching a high dose methotrexate is mainly predicted by folate suppletion. This is most likely explained by a reduction of toxicity. Our results suggest that when using folate adjuvant therapy, a weekly methotrexate dose of > 12.5 mg/week will be reached in 68%. Thus, with adjuvant folate, starting methotrexate therapy at a weekly dose of 15 mg seems justified.

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