Rapid tapering of high-dose prednisone appears to be a feasible, safe, and effective option for people with moderate-to-severe generalized myasthenia gravis on a combination of corticosteroids and immunosuppressants, according to data from a Phase 4 trial.
These findings were reported in the study, “Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis,” published in the journal JAMA Neurology.
Acetylcholinesterase inhibitors like Mestinon (pyridostigmine), which works to counter the blocking of receptors on muscle cells due to the disease and driving muscle weakness, are usually the first-line treatments for myasthenia gravis (MG).
Patients with moderate-to-severe generalized MG (gMG) who fail to respond to these treatments, or require mechanic ventilation, can require a combination of corticosteroids and an immunosuppressive agent, usually azathioprine.
In treating moderate-to-severe MG, the corticosteroid prednisone is usually increased to a standard dose (typically, 0.75 mg/kg), and then gradually tapered once the patient reaches what is called a minimal manifestation status (MMS). People with this status cease to experience most disease symptoms and functional limitations, although they still show some signs of muscle weakness.
Despite being effective, this slow-tapering regimen results in an extended period of treatment with a high cumulative dose of corticosteroids, which has been associated with “significant complications,” the study noted.
“Reducing or even discontinuing prednisone treatment without destabilizing MG is therefore a therapeutic goal in generalized MG,” its researchers wrote.
Investigators report the findings of MYACOR (NCT00987116), a Phase 4 trial to determine whether a rapid tapering of high-dose prednisone would be superior to the standard slow-tapering regimen at increasing the proportion of patients achieving MMS without relapsing and requiring additional prednisone treatment.
During MYACOR, adults with moderate-to-severe gMG were randomly assigned to either a slow or rapid tapering of an oral prednisone. Because the study was single-blind, MG status was assessed by a rater unaware of the patients’ respective treatment groups.
Those in the slow-tapering group were given prednisone at an initial dose of 10 mg, which was gradually increased in 10 mg increments (up to 1.5 mg/kg) every other day, with a maximum dose set at 100 mg.
Patients in the rapid-tapering group received prednisone at an initial daily dose of 0.75 mg/kg, followed by an early, quick decrease once their health status improved.
All patients were also given up to 3 mg/kg per day of the immunosuppressant azathioprine.
Of the 117 people enrolled in the study, 58 were placed in the slow-tapering group and 59 in the rapid-tapering group. More than half (53%) of these patients were men, with a median age of 65.
Compared to the slow-tapering group, a significantly higher proportion of rapid-tapering patients reached MMS without additional prednisone use or a relapse at 15 months (9% vs. 39%).
The cumulative corticosteroid dose reduction for rapid-tapering group patients no longer amounted to an average of 1,898 mg per patient over a year, corresponding to a daily dose reduction of 5.3 mg.
The number of serious side effects was not significantly different between slow-tapering (22%) and rapid-tapering patients (36%). More cases of diabetes were reported in the rapid-tapering group, four as opposed to two in the slow group, but the researchers noted that there was a greater prevalence of diabetes among these patients at the study’s start.
A total of three deaths were reported; two involved patients in the slow-tapering group. Further details were not given.
Despite acknowledging the study might be limited by its short follow-up and single-blind nature due to the lack of a placebo group, the investigators said this work provided “useful information on how prednisone tapering could be managed in patients with generalized MG treated with azathioprine.”
“The findings of this … trial support the use of rapid tapering of prednisone in patients with generalized MG requiring combined corticosteroid and azathioprine therapy [and] … warrant testing of a more rapid-tapering regimen in a future trial,” they wrote.
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