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

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dc.contributor.authorHeckmann, Jeannineen_ZA
dc.contributor.authorRawoot, Amanullahen_ZA
dc.contributor.authorBateman, Kathleenen_ZA
dc.contributor.authorRenison, Rudien_ZA
dc.contributor.authorBadri, Motasimen_ZA
dc.date.accessioned2015-10-28T06:52:13Z
dc.date.available2015-10-28T06:52:13Z
dc.date.issued2011en_ZA
dc.description.abstractBACKGROUND: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-27-0411-2436en_ZA
dc.identifier.apacitationHeckmann, J., Rawoot, A., Bateman, K., Renison, R., & Badri, M. (2011). A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis. <i>BMC Neurology</i>, http://hdl.handle.net/11427/14433en_ZA
dc.identifier.chicagocitationHeckmann, Jeannine, Amanullah Rawoot, Kathleen Bateman, Rudi Renison, and Motasim Badri "A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis." <i>BMC Neurology</i> (2011) http://hdl.handle.net/11427/14433en_ZA
dc.identifier.citationHeckmann, J. M., Rawoot, A., Bateman, K., Renison, R., & Badri, M. (2011). A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis. BMC neurology, 11(1), 97.en_ZA
dc.identifier.ris TY - Journal Article AU - Heckmann, Jeannine AU - Rawoot, Amanullah AU - Bateman, Kathleen AU - Renison, Rudi AU - Badri, Motasim AB - 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 DA - 2011 DB - OpenUCT DO - 10.1186/1471-2377-11-97 DP - University of Cape Town J1 - BMC Neurology LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis TI - A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis UR - http://hdl.handle.net/11427/14433 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14433
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2377-11-97
dc.identifier.vancouvercitationHeckmann J, Rawoot A, Bateman K, Renison R, Badri M. A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis. BMC Neurology. 2011; http://hdl.handle.net/11427/14433.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDivision of Neurologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2011 Heckmann et al; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Neurologyen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcneurol/en_ZA
dc.subject.otherAzathioprineen_ZA
dc.subject.otherImmunosuppressive Agentsen_ZA
dc.subject.otherMethotrexateen_ZA
dc.subject.otherPrednisoneen_ZA
dc.titleA single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravisen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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