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A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis
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 Afr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170595/ https://www.ncbi.nlm.nih.gov/pubmed/21819556 http://dx.doi.org/10.1186/1471-2377-11-97 |
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author | Heckmann, Jeannine M Rawoot, Amanullah Bateman, Kathleen Renison, Rudi Badri, Motasim |
author_facet | Heckmann, Jeannine M Rawoot, Amanullah Bateman, Kathleen Renison, Rudi Badri, Motasim |
author_sort | Heckmann, Jeannine M |
collection | PubMed |
description | 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 |
format | Online Article Text |
id | pubmed-3170595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-31705952011-09-11 A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis Heckmann, Jeannine M Rawoot, Amanullah Bateman, Kathleen Renison, Rudi Badri, Motasim BMC Neurol Research Article 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 BioMed Central 2011-08-05 /pmc/articles/PMC3170595/ /pubmed/21819556 http://dx.doi.org/10.1186/1471-2377-11-97 Text en Copyright ©2011 Heckmann et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Heckmann, Jeannine M Rawoot, Amanullah Bateman, Kathleen Renison, Rudi Badri, Motasim A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis |
title | A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis |
title_full | A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis |
title_fullStr | A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis |
title_full_unstemmed | A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis |
title_short | A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis |
title_sort | single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170595/ https://www.ncbi.nlm.nih.gov/pubmed/21819556 http://dx.doi.org/10.1186/1471-2377-11-97 |
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