An open-label strategy trial in patients with rheumatoid arthritis (RA) has found that intensive methotrexate (MTX) therapy with close control and computerised decision-support gave higher response rates than a standard treatment strategy, however adverse effects were more of a problem.
The authors of this study noted that while MTX was a mainstay of treatment in RA, determination of disease activity and dose selection were often carried out in an ad hoc manner.
They hypothesised that standardised criteria and protocols, with the addition of computerised decision support, would allow a more intensive treatment regimen to be used with the prospect of higher remission rates.
Their study involved all consenting patients who had early RA and presented to the participating clinics between 1999 and 2003.
Patients were randomised to conventional or intensive strategy groups, and both groups received MTX at a starting dose of 7.5mg weekly with the object of inducing remission.
Those in the conventional group were seen every three months and were treated according to standard practice of the time; those in the intensive group were seen monthly and MTX dose was tailored to the patient according to predefined response criteria using the decision-support computer program.
Cyclosporin was added as the second-line treatment if necessary. The primary major outcome was the number of patients in remission for at least three months at any time during the two-year trial – power calculation indicated that 100 patients per group would be required; to allow for dropouts, 150 per group were recruited.
At the end of the study, 299 patients had been recruited (intensive treatment, n=151; conventional treatment, n= 148). More patients withdrew from the intensive group than from the conventional group (59 vs. 35), most frequently due to drug adverse effects (27 vs. 11), leaving 92 vs. 113 who completed the two-year period.
Significantly more patients in the intensive group entered remission for at least three months during the study period – 35% vs. 14% by the end of the first year, and 50% vs. 37% at the end of the second.
The mean time to first remission was shorter in the intensive group (10.4 vs. 14.3 months) and duration of remission was longer (11.6 vs. 9.1 months).
Adverse effects were frequent in both groups, however these were generally tolerated. The strategy allowed MTX dose reduction to occur in 56% of the intensive group due to sustained response.
The authors concluded that the intensive strategy was capable of giving faster response in a greater proportion of patients compared to the conventional strategy.
They noted the increased incidence of adverse effects, a significant proportion of which were associated with the start of cyclosporin therapy, but suggested that MTX tolerance might be improved by increasing the dose of folic acid.
The decision-support system was well accepted and considered to be a potentially helpful tool for practice.