The proportion of patients treated with prednisone and the prednisone dose tended to be lower in the rapid-tapering group at 15 months compared to slow-tapering arm.
Results from the multicenter, parallel, single-blind, randomized MYACOR clinical trial (NCT00987116) revealed that rapid tapering of prednisone appears to be feasible, well-tolerated, and associated with good outcome among patients with moderate to severe generalized myasthenia gravis (MG).
The study included 117 patients with moderate to severe generalized MG who required high-dose prednisone with azathioprine therapy who were randomized 1:1 to either the slow tapering arm (n = 58) or the rapid-tapering arm. Led by Tarek Sharshar, MD, PhD, Neuro-anesthesiology and Intensive Care Medicine, Sainte-Anne Hospital, the objective of the study was to compare the efficacy of the standard slow-tapering regimen to that of high-tapering regimen, which had not been yet validated.
Patients in the slow-tapering arm had a gradual increase of the prednisone dose to 1.5 mg/kg every other day and a slow decrease once minimal manifestation status (MMS) of MG was attained, whereas those in the rapid-tapering arm had immediate high-dose daily administration of prednisone 0.75 mg/kg, followed by an earlier and rapid decrease once minimal MG status was attained. Azathioprine, up to a maximum dose of 3 mg/kg/d, was prescribed for all participants.
The primary outcome, attainment of minimal manifestation status of MG without prednisone at 12 months, was observed in 23 patients (36%) in the rapid-tapering group, compared to 5 (9%) in the slow-tapering arm, with a risk ratio of 3.61 (95% CI, 1.64–7.97; P < .01) after adjusting for center and thymectomy. In addition to the minimal manifestation of the disease, the primary outcome measure also required patients to have no clinical relapses at the 15-month mark.
"Researching the best prednisone-tapering scheme is not only a major issue for patients with MG but also for other autoimmune or inflammatory diseases, because validated prednisone-tapering regimens are scarce,” Sharshar et al wrote.
Conducted between June 1, 2009, and July 31, 2013, the study also examined secondary outcomes such as the cumulative dose of prescribed prednisone over 12 months, the proportion of participants with MMS over 12 months, the delay in reaching MMS, and the rate and time of MG worsening and exacerbations within the first 15 months.
Sharshar and colleagues found that rapid tapering allowed sparing of a mean of 1898 mg (95% CI, –3121 to –461 mg) of prednisone over 1 year per patient (5.3 mg/d; P = .03).
Additionally, at 15 months, the proportion of participants treated with prednisone and the prednisone dose tended to be lower in the rapid-tapering group (proportion: slow tapering, 28 [53%] vs rapid tapering, 19 [34%]; P = .07; dose: slow tapering, 2 mg [interquartile range (IQR), 0–10 mg] vs rapid tapering, 0 mg [IQR, 0–4 mg]; P = .06).
The rate of MG exacerbation (slow tapering, 6 [11%] vs rapid tapering, 6 [11%]; P = .99) or worsening (slow tapering, 26 [50%] vs rapid tapering, 30 [54%]; P = .72) between baseline and 15 months did not differ significantly between the 2 groups, nor did the use of plasmapheresis or intravenous immunoglobulin (slow tapering, 6 [11%] vs rapid tapering, 6 [10%]; P = .99).
There were 3 deaths reported in the study, 2 of which in the slow-tapering group. Malignant stroke was the cause of death in 1 patient and acute respiratory failure in 2 patients. Serious adverse events (SAEs) were not statistically significantly more frequent in the slow- vs rapid-tapering group (13 [22%] vs 21 [36%]; P = .15). Researchers also noted that the overall number of complications did not differ significantly between the 2 groups (slow tapering, 22% vs rapid tapering, 36%; P = .15).