An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis

D. B. Sanders, I. K. Hart, R. Mantegazza, S. S. Shukla, Z. A. Siddiqi, M. H V De Baets, A. Melms, M. W. Nicolle, N. Solomons, David P Richman

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

Background: This prospective, randomized, double-blind, placebo-controlled, phase III trial assessed the efficacy, safety, and tolerability of mycophenolate mofetil (MMF) as a steroid-sparing agent in patients with myasthenia gravis (MG). Methods: Patients with acetylcholine receptor antibody-positive class II-IVa MG (MG Foundation of America [MGFA] criteria) taking corticosteroids for at least 4 weeks were randomized to MMF (2 g/day) or placebo for 36 weeks. The primary endpoint was a composite measure defined as achievement of minimal manifestations or pharmacologic remission (MGFA post-intervention status), with reduction of corticosteroid dose on a set schedule. Secondary endpoints included disease severity, quality-of-life scores, and safety. Results: A total of 44% of MMF-treated (n = 88) and 39% of placebo-receiving (n = 88) patients achieved the primary endpoint (p = 0.541). Improvements in mean quantitative MG, MG activities of daily living, and 36-item Short-Form health survey scores were similar in both groups. Numbers of adverse events were similar in both groups. The most commonly reported adverse events in the MMF-treated group were headache (12.5%) and worsening of MG (11.4%), and in the placebo group, worsening of MG (20.5%) and diarrhea (10.2%). Conclusions: Initiation of mycophenolate mofetil (MMF) treatment was not superior to placebo in maintaining myasthenia gravis (MG) control during a 36-week schedule of prednisone tapering. There were no significant differences in the primary or secondary endpoints between the study groups. MMF was well tolerated and adverse events were consistent with previous studies. Experience from this large, international, multicenter, phase III study employing full MG Foundation of America guidelines will aid the design of future MG studies.

Original languageEnglish (US)
Pages (from-to)400-406
Number of pages7
JournalNeurology
Volume71
Issue number6
DOIs
StatePublished - Aug 5 2008

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Mycophenolic Acid
Myasthenia Gravis
Placebos
Appointments and Schedules
Adrenal Cortex Hormones
Safety
Immunoglobulin Isotypes
Proxy
Cholinergic Receptors
Activities of Daily Living
Prednisone
Health Surveys
Headache
Diarrhea
Steroids
Quality of Life
Guidelines

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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Sanders, D. B., Hart, I. K., Mantegazza, R., Shukla, S. S., Siddiqi, Z. A., De Baets, M. H. V., ... Richman, D. P. (2008). An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. Neurology, 71(6), 400-406. https://doi.org/10.1212/01.wnl.0000312374.95186.cc

An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. / Sanders, D. B.; Hart, I. K.; Mantegazza, R.; Shukla, S. S.; Siddiqi, Z. A.; De Baets, M. H V; Melms, A.; Nicolle, M. W.; Solomons, N.; Richman, David P.

In: Neurology, Vol. 71, No. 6, 05.08.2008, p. 400-406.

Research output: Contribution to journalArticle

Sanders, DB, Hart, IK, Mantegazza, R, Shukla, SS, Siddiqi, ZA, De Baets, MHV, Melms, A, Nicolle, MW, Solomons, N & Richman, DP 2008, 'An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis', Neurology, vol. 71, no. 6, pp. 400-406. https://doi.org/10.1212/01.wnl.0000312374.95186.cc
Sanders DB, Hart IK, Mantegazza R, Shukla SS, Siddiqi ZA, De Baets MHV et al. An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. Neurology. 2008 Aug 5;71(6):400-406. https://doi.org/10.1212/01.wnl.0000312374.95186.cc
Sanders, D. B. ; Hart, I. K. ; Mantegazza, R. ; Shukla, S. S. ; Siddiqi, Z. A. ; De Baets, M. H V ; Melms, A. ; Nicolle, M. W. ; Solomons, N. ; Richman, David P. / An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. In: Neurology. 2008 ; Vol. 71, No. 6. pp. 400-406.
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abstract = "Background: This prospective, randomized, double-blind, placebo-controlled, phase III trial assessed the efficacy, safety, and tolerability of mycophenolate mofetil (MMF) as a steroid-sparing agent in patients with myasthenia gravis (MG). Methods: Patients with acetylcholine receptor antibody-positive class II-IVa MG (MG Foundation of America [MGFA] criteria) taking corticosteroids for at least 4 weeks were randomized to MMF (2 g/day) or placebo for 36 weeks. The primary endpoint was a composite measure defined as achievement of minimal manifestations or pharmacologic remission (MGFA post-intervention status), with reduction of corticosteroid dose on a set schedule. Secondary endpoints included disease severity, quality-of-life scores, and safety. Results: A total of 44{\%} of MMF-treated (n = 88) and 39{\%} of placebo-receiving (n = 88) patients achieved the primary endpoint (p = 0.541). Improvements in mean quantitative MG, MG activities of daily living, and 36-item Short-Form health survey scores were similar in both groups. Numbers of adverse events were similar in both groups. The most commonly reported adverse events in the MMF-treated group were headache (12.5{\%}) and worsening of MG (11.4{\%}), and in the placebo group, worsening of MG (20.5{\%}) and diarrhea (10.2{\%}). Conclusions: Initiation of mycophenolate mofetil (MMF) treatment was not superior to placebo in maintaining myasthenia gravis (MG) control during a 36-week schedule of prednisone tapering. There were no significant differences in the primary or secondary endpoints between the study groups. MMF was well tolerated and adverse events were consistent with previous studies. Experience from this large, international, multicenter, phase III study employing full MG Foundation of America guidelines will aid the design of future MG studies.",
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AU - Sanders, D. B.

AU - Hart, I. K.

AU - Mantegazza, R.

AU - Shukla, S. S.

AU - Siddiqi, Z. A.

AU - De Baets, M. H V

AU - Melms, A.

AU - Nicolle, M. W.

AU - Solomons, N.

AU - Richman, David P

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N2 - Background: This prospective, randomized, double-blind, placebo-controlled, phase III trial assessed the efficacy, safety, and tolerability of mycophenolate mofetil (MMF) as a steroid-sparing agent in patients with myasthenia gravis (MG). Methods: Patients with acetylcholine receptor antibody-positive class II-IVa MG (MG Foundation of America [MGFA] criteria) taking corticosteroids for at least 4 weeks were randomized to MMF (2 g/day) or placebo for 36 weeks. The primary endpoint was a composite measure defined as achievement of minimal manifestations or pharmacologic remission (MGFA post-intervention status), with reduction of corticosteroid dose on a set schedule. Secondary endpoints included disease severity, quality-of-life scores, and safety. Results: A total of 44% of MMF-treated (n = 88) and 39% of placebo-receiving (n = 88) patients achieved the primary endpoint (p = 0.541). Improvements in mean quantitative MG, MG activities of daily living, and 36-item Short-Form health survey scores were similar in both groups. Numbers of adverse events were similar in both groups. The most commonly reported adverse events in the MMF-treated group were headache (12.5%) and worsening of MG (11.4%), and in the placebo group, worsening of MG (20.5%) and diarrhea (10.2%). Conclusions: Initiation of mycophenolate mofetil (MMF) treatment was not superior to placebo in maintaining myasthenia gravis (MG) control during a 36-week schedule of prednisone tapering. There were no significant differences in the primary or secondary endpoints between the study groups. MMF was well tolerated and adverse events were consistent with previous studies. Experience from this large, international, multicenter, phase III study employing full MG Foundation of America guidelines will aid the design of future MG studies.

AB - Background: This prospective, randomized, double-blind, placebo-controlled, phase III trial assessed the efficacy, safety, and tolerability of mycophenolate mofetil (MMF) as a steroid-sparing agent in patients with myasthenia gravis (MG). Methods: Patients with acetylcholine receptor antibody-positive class II-IVa MG (MG Foundation of America [MGFA] criteria) taking corticosteroids for at least 4 weeks were randomized to MMF (2 g/day) or placebo for 36 weeks. The primary endpoint was a composite measure defined as achievement of minimal manifestations or pharmacologic remission (MGFA post-intervention status), with reduction of corticosteroid dose on a set schedule. Secondary endpoints included disease severity, quality-of-life scores, and safety. Results: A total of 44% of MMF-treated (n = 88) and 39% of placebo-receiving (n = 88) patients achieved the primary endpoint (p = 0.541). Improvements in mean quantitative MG, MG activities of daily living, and 36-item Short-Form health survey scores were similar in both groups. Numbers of adverse events were similar in both groups. The most commonly reported adverse events in the MMF-treated group were headache (12.5%) and worsening of MG (11.4%), and in the placebo group, worsening of MG (20.5%) and diarrhea (10.2%). Conclusions: Initiation of mycophenolate mofetil (MMF) treatment was not superior to placebo in maintaining myasthenia gravis (MG) control during a 36-week schedule of prednisone tapering. There were no significant differences in the primary or secondary endpoints between the study groups. MMF was well tolerated and adverse events were consistent with previous studies. Experience from this large, international, multicenter, phase III study employing full MG Foundation of America guidelines will aid the design of future MG studies.

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