Dose escalation of parenteral MTX in active RA that has been unresponsive to conventional doses of MTX

[Guest guest]

Arthritis Rheum. 2004 Feb;50(2):364-71.

Dose escalation of parenteral methotrexate in active rheumatoid

arthritis that has been unresponsive to conventional doses of

methotrexate: A randomized, controlled trial.

Lambert CM, Sandhu S, Lochhead A, Hurst NP, McRorie E, Dhillon V.

University of Edinburgh, Edinburgh, UK.

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.

PMID: 14872477

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org