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Original Investigation
February 8, 2021

Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis: A Randomized Clinical Trial

Author Affiliations
  • 1Neuro-anesthesiology and Intensive Care Medicine, GHU-Paris, Sainte-Anne Hospital, Paris-17 Université de Paris, Paris, France
  • 2General Intensive Care Unit, APHP, Raymond Poincaré Hospital, University of Versailles Saint-Quentin en Yvelines, Garches, France
  • 3Experimental Neuropathology, Infection and Epidemiology Department, Institut Pasteur, Paris, France
  • 4Center for Clinical Epidemiology, Assistance Publique Hôpitaux de Paris, Hôtel Dieu Hospital, University Paris Descartes–France, Paris, France
  • 5Department of Neurology, Neuro-ICU, APHP-Paris-Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France
  • 6Department of Neurology, University Hospital, Strasbourg, France
  • 7Department of Neurology, Rothschild Ophthalmologic Foundation, Paris, France
  • 8Department of Neurology, Neuro-ICU, APHP-Paris-Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France
  • 9France Department of Neurology, University Hospital, Angers, France
  • 10Clinical Research Unit, Ambroise Paré Hospital, University of Versailles Saint-Quentin en Yvelines, Boulogne-Billancourt, France
  • 11Neuromuscular Investigation Centre, Institute of Myology, Pitié-Salpêtrière Hospital, Paris, France
JAMA Neurol. 2021;78(4):426-433. doi:10.1001/jamaneurol.2020.5407
Key Points

Question  Can a rapid-tapering regimen of prednisone be used in patients with generalized myasthenia gravis?

Findings  In a single-blind, parallel, randomized clinical trial including 117 patients with generalized myasthenia gravis, the rapid-tapering regimen was associated with a significantly greater proportion of patients who reached the minimal manifestation status of generalized myasthenia gravis and did not require prednisone treatment at 12 and 15 months.

Meaning  The rapid tapering of prednisone therapy appears to be feasible, beneficial, and safe in patients with generalized myasthenia gravis and warrants testing in other autoimmune diseases.

Abstract

Importance  The tapering of prednisone therapy in generalized myasthenia gravis (MG) presents a therapeutic dilemma; however, the recommended regimen has not yet been validated.

Objective  To compare the efficacy of the standard slow-tapering regimen of prednisone therapy with a rapid-tapering regimen.

Design  From June 1, 2009, to July 31, 2013, a multicenter, parallel, single-blind randomized trial was conducted to compare 2 regimens of prednisone tapering. Data analysis was conducted from February 18, 2019, to January 23, 2020. A total of 2291 adults with a confirmed diagnosis of moderate to severe generalized MG at 7 specialized centers in France were assessed for eligibility.

Interventions  The slow-tapering arm included a gradual increase of the prednisone dose to 1.5 mg/kg every other day and a slow decrease once minimal manifestation status of MG was attained. The rapid-tapering arm consisted of immediate high-dose daily administration of prednisone, 0.75 mg/kg, followed by an earlier and rapid decrease once improved MG status was attained. Azathioprine, up to a maximum dose of 3 mg/kg/d, was prescribed for all participants.

Main Outcomes and Measures  The primary outcome was attainment of minimal manifestation status of MG without prednisone at 12 months and without clinical relapse at 15 months. Intention-to-treat analysis was conducted.

Results  Of the 2291 patients assessed, 2086 did not fulfill the inclusion criteria, 87 declined to participate, and 1 patient registered after trial closure. A total of 117 patients (58 in the slow-tapering arm and 59 in the rapid-tapering arm) were selected for inclusion by MG specialists and were randomized. The population included 62 men (53%); median age was 65 years (interquartile range, 35-69 years). The proportion of patients having met the primary outcome was higher in the rapid- vs slow-tapering arm (23 [39%] vs 5 [9%]), with a risk ratio of 3.61 (95% CI, 1.64-7.97; P < .001) after adjusting for center and thymectomy. The rapid-tapering regimen allowed sparing of a mean of 1898 mg (95% CI, −3121 to −461 mg) of prednisone over 1 year (ie, 5.3 mg/d per patient, P = .03). The number of serious adverse events did not differ significantly between the slow- vs rapid-tapering group (13 [22%] vs 21 [36%], P = .15).

Conclusions and Relevance  In patients with moderate to severe generalized MG who require high-dose prednisone with azathioprine therapy, rapid tapering of prednisone appears to be feasible, well tolerated, and associated with a good outcome.

Trial Registration  ClinicalTrials.gov Identifier: NCT00987116

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    1 Comment for this article
    Considerations to take into account regarding this article
    Neetika Sharma, MD | Postgraduate Institute of Medical Education and Research (PGIMER) CHANDIGARH, INDIA
    1.Sample size calculation-considering it as a superiority trial one has to use a large sample size.
    2. Concomitant effect of pyridostigmine and azathioprine not taken into account.
    3.More diabetic patients were in rapid tapering group.
    4. Used dosages are different in slow and rapid tapering group.
    CONFLICT OF INTEREST: None Reported
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