دورية أكاديمية
Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: a randomized, controlled trial.
العنوان: | Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: a randomized, controlled trial. |
---|---|
المؤلفون: | Lambert CM; University of Edinburgh, Edinburgh, UK. michael.lambert@luht.scot.nhs.uk, Sandhu S, Lochhead A, Hurst NP, McRorie E, Dhillon V |
المصدر: | Arthritis and rheumatism [Arthritis Rheum] 2004 Feb; Vol. 50 (2), pp. 364-71. |
نوع المنشور: | Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 0370605 Publication Model: Print Cited Medium: Print ISSN: 0004-3591 (Print) Linking ISSN: 00043591 NLM ISO Abbreviation: Arthritis Rheum Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Original Publication: Atlanta [etc.] Arthritis Foundation [etc.] |
مواضيع طبية MeSH: | Arthritis, Rheumatoid/*drug therapy , Drug Resistance/*drug effects , Methotrexate/*therapeutic use, Arthritis, Rheumatoid/pathology ; Arthritis, Rheumatoid/physiopathology ; Dose-Response Relationship, Drug ; Double-Blind Method ; Female ; Health Status ; Humans ; Injections, Intramuscular ; Joints/drug effects ; Joints/pathology ; Joints/physiopathology ; Male ; Methotrexate/administration & dosage ; Middle Aged ; Severity of Illness Index ; Surveys and Questionnaires ; Treatment Outcome |
مستخلص: | Objective: To examine whether dose escalation of intramuscular (IM) methotrexate (MTX) up to 45 mg/week improves disease control in patients who have active rheumatoid arthritis (RA) despite receiving conventional doses (15 mg/week) of IM MTX, and to obtain preliminary data on patient tolerability and adverse effects of higher doses of IM MTX. Methods: Patients >18 years of age who had active RA, defined as a European League Against Rheumatism (EULAR) Disease Activity Score in 28 joints (DAS28) of >3.2, and who had received 15-20 mg/week of oral MTX for at least 2 months were switched (week 0) to 15 mg/week of IM MTX for 6 weeks. Patients whose DAS28 remained >3.2 at both week 4 and week 6 were randomized, in a double-blind manner, either to continue to receive 15 mg/week IM MTX with monthly placebo escalation or to receive escalating doses of IM MTX monthly up to 45 mg/week. The dose of MTX or placebo was escalated every 4 weeks if the DAS28 was >2.5. Safety assessments and determination of the DAS28 were performed every 2 weeks and monthly, respectively. Disease activity parameters from the American College of Rheumatology (ACR) core disease activity set and health status as recorded on the Medical Outcomes Study Short-Form 12 were determined at baseline (week 0) and final assessment (week 22). The primary outcome was the percentage of patients in each group achieving a target DAS28 of <3.2. Secondary outcomes comprised the percentage of patients whose DAS28 improved by >1.2, the percentage of patients achieving a 20% improvement in the ACR core disease activity measures (ACR20), and the percentage of patients achieving a good response, a moderate response, or no response in accordance with the EULAR response criteria. Results: Sixty-four patients were eligible for entry and were switched from oral MTX to 15 mg/week IM MTX. At baseline, the mean +/- SD DAS28 was 5.6 +/- 0.88; after 6 weeks of IM MTX, the DAS28 had improved by a mean of 0.42 (95% confidence interval [95% CI] 0.15-0.69). At 6 weeks, 54 patients still had a DAS28 of >3.2 and were therefore eligible for randomization. By 22 weeks, 1 patient (3.7%) in each group achieved the primary outcome of a DAS28 <3.2 (95% CI for the difference between the groups -15% to +15%). Five patients (18.5%) in each group showed an improvement of >1.2 in the DAS28 (95% CI for the difference between the groups -18% to +18%). One patient (3.7%) in each group achieved an ACR20 response, but none achieved a good response as defined by the EULAR response criteria. One patient in each group had a serious adverse reaction; minor adverse reactions were more frequently reported in the dose escalation group. Conclusion: Switching from oral to parenteral MTX 15 mg/week results in a minor improvement in disease control. For patients with active RA receiving 15 mg/week IM MTX, increasing the dose up to 45 mg/week does not improve disease control. Higher doses of IM MTX were generally well tolerated and not associated with an increase in serious adverse reactions to the drug. |
المشرفين على المادة: | YL5FZ2Y5U1 (Methotrexate) |
تواريخ الأحداث: | Date Created: 20040212 Date Completed: 20040302 Latest Revision: 20151119 |
رمز التحديث: | 20221213 |
DOI: | 10.1002/art.20167 |
PMID: | 14872477 |
قاعدة البيانات: | MEDLINE |
كن أول من يترك تعليقا!