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.