Open Access Research article

A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis

Jeannine M Heckmann1*, Amanullah Rawoot1, Kathleen Bateman1, Rudi Renison1 and Motasim Badri23

Author Affiliations

1 Department of Medicine, Division of Neurology, University of Cape Town, Observatory, Cape Town, 7925, South Africa

2 Department of Medicine, University of Cape Town, Observatory, Cape Town, 7925, South Africa

3 Department of Basic Sciences, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia

For all author emails, please log on.

BMC Neurology 2011, 11:97  doi:10.1186/1471-2377-11-97

Published: 5 August 2011

Abstract

Background

Long-term immunosuppression is often required in myasthenia gravis (MG). There are no published trials using methotrexate (MTX) in MG. The steroid-sparing efficacy of azathioprine (AZA) has been demonstrated after 18-months of starting therapy. However, AZA is considered expensive in Africa. We evaluated the steroid-sparing efficacy of MTX (17.5 mg weekly) compared with AZA (2.5 mg/kg daily) in subjects recently diagnosed with generalized MG by assessing their average monthly prednisone requirements.

Methods

The primary outcome was the average daily prednisone requirement by month between the two groups. Prednisone was given at the lowest dose to manage MG symptoms and adjusted as required according to protocol. Single-blinded assessments were performed 3-monthly for 2-years to determine the quantitative MG score and the MG activities of daily living score in order to determine those with minimal manifestations of MG.

Results

Thirty-one subjects (AZA n = 15; MTX n = 16) satisfied the inclusion criteria but only 24 were randomized. Baseline characteristics were similar. There was no difference between the AZA- and MTX-groups in respect of prednisone dosing (apart from months 10 and 12), in quantitative MG Score improvement, proportions in sustained remission, frequencies of MG relapses, or adverse reactions and/or withdrawals. The MTX-group received lower prednisone doses between month 10 (p = 0.047) and month 12 (p = 0.039). At month 12 the prednisone dose per kilogram bodyweight in the MTX-group (0.15 mg/kg) was half that of the AZA-group (0.31 mg/kg)(p = 0.019).

Conclusions

This study provides evidence that in patients with generalized MG methotrexate is an effective steroid-sparing agent 10 months after treatment initiation. Our data suggests that in generalized MG methotrexate has similar efficacy and tolerability to azathioprine and may be the drug of choice in financially constrained health systems.

Trial registration

SANCTR:DOH-27-0411-2436