Comparison of two schedules for administering oral low-dose methotrexate (weekly versus every-other-week) in patients with rheumatoid arthritis in remission: A twenty-four-week, single-blind, randomized study

Abstract

Objective. To compare the efficacy of 2 low-dose oral methotrexate (MTX) schedules in maintaining remission in patients with rheumatoid arthritis (RA).Methods. Patients with RA were included if they were receiving treatment with weekly MTX for at least 9 months and the RA was in remission (defined by American College of Rheumatology [ACR] criteria) for at least 6 months. Patients were stratified by treatment and randomly assigned to weekly or every-other-weekly (EOW; reducing their monthly dose by half) treatment with MTX. Patients were evaluated by a rheumatologist (blinded to the treatment schedule) at baseline and at 6, 12, and 24 weeks. The evaluations included joint counts, Ritchie Articular Index, Health Assessment Questionnaire Disability Index, physician's and patient's global health assessments, visual analog scale for pain, and incidence of adverse effects. Laboratory evaluations were done at baseline and at week 24.Results. Fifty-one patients were included (26 taking weekly MTX, 25 taking EOW MTX). Baseline comparisons showed no differences between the groups. The mean duration of RA was <3 years in both groups, and they had been started on weekly MTX treatment early after diagnosis. After 24 weeks, >90% of the patients in both groups continued in remission. Evaluations of disease activity at 6 and 12 weeks showed no betweengroup differences. EOW MTX patients who experienced relapse were switched back to weekly MTX, and after a few weeks, their RA was again controlled. The incidence of adverse effects was slightly higher in the weekly MTX group, although the difference did not reach statistical significance. The observed laboratory values were very similar for both groups, except for the serum aspartate aminotransferase and alanine aminotransferase levels, which decreased in the EOW MTX group and were statistically significant at week 24 (P ‫؍‬ 0.04 and P ‫؍‬ 0.006, respectively).Conclusion. EOW MTX represents a valid therapeutic alternative for a specific subgroup of RA patients, as outlined by the ACR remission criteria. Patients with a short disease duration who were treated early after disease onset with weekly MTX and who achieve sustained remission have a higher probability of success with the EOW MTX schedule.

Pharmacokinetic consideration of synthetic DMARDs in rheumatoid arthritis

“…Additionally, no substantial differentiation in PK parameters of MTX was noted with regard to the time of therapy [45]. Similarly, comparison of weekly and every other week regimen by Luis et al concluded that there is no significant difference between the two drug schedules with regard to the efficacy [46]. No major difference in the clinical response as well as the overall change in CRP values was found, when a low daily dose was compared with weekly pulse dose.…”

Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature

“…However, Pandya et al 22 showed that a twice weekly schedule of methotrexate had no advantage over a weekly schedule. In contrast, a change to every other week dosing was possible in patients stable or in remission on methotrexate, although some experienced disease flares 20 21. In conclusion, weekly methotrexate is the preferred frequency of administration, with a potential switch to a fortnightly schedule in the case of sustained remission.…”

Disease activity and therapeutic drug monitoring of polyglutamates of methotrexate after daily or weekly administration of low‐dose methotrexate in patients recently diagnosed with rheumatoid arthritis

“…Additionally, previous studies have reported the high incidence of medication error associated with the weekly dose of MTX 14,20,21 …”

“…The main reasons for non‐adherence to MTX are intolerance, forgetfulness and concern about long‐term safety 18 . Some strategies have been proposed to reduce the adverse events or medication errors associated with MTX and improve treatment adherence; for example, by modifying dosage scheme every other week or twice weekly 19–21 . No previous studies comparing clinical outcomes of a total dose divided daily versus the current weekly dosing schedule in RA patients have been performed.…”