Dose Escalation of Intramuscular (im) Methotrexate (MTX) for Patients with Active Rheumatoid Arthritis (RA) does not Improve Disease Control - a

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Dose Escalation of Intramuscular (im) Methotrexate (MTX) for Patients with

Active Rheumatoid Arthritis (RA) does not Improve Disease Control - a

Randomised Placebo Controlled Trial

Category: 17 RA—treatment

Presentation Time: Saturday, 2:45 p.m. - 3:00 p.m.

C M Lambert, S Sandhu, A Lochhead, N P Hurst, E McRorie, V B Dhillon

University of Edinburgh, Edinburgh, United Kingdom

Presentation Number: 465

Keywords: methotrexate, dose escalation

A dose response relationship for oral MTX (up to 22mg/wk) in patients with

active RA has previously been demonstrated (J Rheumatol 1989;16:313-320).

The safety and efficacy of higher doses of im MTX are unknown.

Aim. To examine whether dose escalation of im MTX from 15mg to 45mg/wk

improves disease control of active RA.

Methods. Inclusion criteria- age > 18yrs with definite RA, active disease

defined by DAS28>3.2 despite MTX 15-20mg/wk orally for 8 weeks followed by

MTX 15mg/wk im for 6 weeks prior to randomisation. All had received at least

one other disease modifying drug (DMARD) for at least 2 months at

therapeutic dose. Exclusion criteria- oral steroid >10mg/day, change in oral

steroid dose or intra-articular steroids within previous 4 weeks.

Randomisation was performed off site and stratified according to steroid

use. Active treatment comprised monthly dose escalation of MTX by 10mg up to

45mg/wk im provided that the DAS28 remained >2.5 units and there was no

contraindication. The control group received stable dose MTX 15mg im with

placebo escalation. All assessments were double blind. All patients received

5mg folic acid/wk and were carefully evaluated for adverse effects. Primary

outcome- % in each group achieving a DAS28 <3.2 units. Secondary outcomes- %

in each group with improvement in DAS28 of >1.2 units, ACR20/50/70 response,

good moderate response defined by EULAR response criteria and change in

health status and disability measured with Short Form 12 and modified HAQ

respectively. DAS was performed monthly and all other assessments at

baseline and twenty two weeks. Sample size- to detect a 50% difference in

the primary outcome with 90% power requires 22 patients per group. Results.

27 patients were randomised to each group. There was no significant

difference in demographic characteristics between control and active

treatment groups for age, gender, disease duration (mean 9.5yrs), number of

previous DMARDs (median 2), % RF positive, % with erosions, number receiving

oral steroids or baseline disease activity. Mean dose of MTX achieved in the

active treatment group was 40mg/wk. There was no significant difference in

the primary outcome between the groups- 3.7% in each group achieved a DAS28

< 3.2 units, and no difference in secondary outcomes- 18.5% in each group

improved in DAS28 by > 1.2 units.

Conclusions. In this study increasing the dose of im MTX from 15mg/wk to

45mg/wk, in RA patients with active disease, did not result in improved

disease control.