Study supports rapid prednisone tapering in patients with generalized myasthenia gravis
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A rapid-tapering prednisone regimen was found to be feasible, well-tolerated and associated with good outcomes in patients with moderate to severe generalized myasthenia gravis, according to findings published in JAMA Neurology.
“The prednisone dosage in treatment of moderate to severe (myasthenia gravis [MG]) is commonly gradually increased to 0.75 mg/kg on alternate days and reduced progressively when minimal manifestation status (MMS) is reached,” Tarek Sharshar, MD, PhD, and colleagues wrote. “This recommended regimen leads to high and prolonged corticosteroid treatment, as the mean daily prednisone dose exceeds 30 mg/d at 15 months and 20 mg/d at 36 months. Although effective, long-term use of corticosteroids is often associated with significant complications. Reducing or even discontinuing prednisone treatment without destabilizing MG is therefore a therapeutic goal in generalized MG.”
While thymectomy and immunosuppressive agents can help decrease the cumulative dose of prednisone patients receive, the dose “usually remains relatively high for several years,” according to Sharshar and colleagues. The researchers “wondered whether different regimens could help wean patients with generalized MG from corticosteroid therapy without compromising efficacy.”
As a result, Sharshar and colleagues conducted a multicenter, single-blind, randomized clinical trial to examine if higher corticosteroid doses given initially, followed by rapid tapering, could increase the number of patients attaining MMS without prednisone at 12 months and without relapsing at 15 months compared with standard slow tapering. They compared two regimens of prednisone tapering in adults with confirmed moderate to severe generalized MG at seven centers in France from February 2019 through January 2020.
Achieving MMS of MG without prednisone at 12 months and without clinical relapse at 15 months served as the primary outcome.
Sharshar and colleagues enrolled 117 patients in the study, including 58 in the slow-tapering arm and 59 in the rapid-tapering arm. The study population comprised 53% men; the median age was 65 years. The researchers noted that treatment groups “were well balanced at baseline” for age, MG characteristics and thymectomy.
Patients in the slow-tapering arm received a gradual uptick in prednisone dose to 1.5 mg/kg every other day and a slow decline following MMS of MG. Patients in the rapid-tapering arm received immediate, high-dose daily prednisone 0.75 mg/kg followed by “an earlier and rapid decrease” in prednisone dose after improvement in MG status. All patients received azathioprine, up to a maximum dose of 3 mg/kg per day.
The primary outcome analysis demonstrated that the number of patients who attained MMS independent of corticosteroid treatment without relapsing at 15 months was significantly higher in the rapid-tapering group (39%) compared with the slow-tapering group (9%), with a risk ratio of 3.61 (95% CI, 1.64-7.97) after adjusting for center and thymectomy. Subgroup analyses demonstrated no interaction with thymectomy or MG duration.
Over the course of 1 year, the rapid-tapering regimen spared a mean of 1,898 mg (95% CI, 3,121 mg to 461 mg) of prednisone. The number of serious adverse events did not differ significantly between the slow-tapering and the rapid-tapering groups, according to the study findings. Sharshar and colleagues reported three deaths, including two in the slow-tapering group.
The study results “support the use of rapid tapering of prednisone in patients with generalized MG requiring combined corticosteroid and azathioprine therapy,” the researchers wrote.
“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 and colleagues wrote. “Our results warrant testing of a more rapid tapering regimen in a future trial. In the meantime, our trial provides useful information on how prednisone tapering could be managed in patients with generalized MG treated with azathioprine.”
Perspective
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Ericka Wong, MD
We know that corticosteroids work for patients with myasthenia gravis. We also know about the significant side effects of corticosteroids, particularly given the length of time these patients typically stay on these medications. Traditionally, a slower taper is considered safer, although there has been no clear consensus on steroid tapering regimens. Sharshar and colleagues found that prednisone can likely be more rapidly tapered in patients with generalized MG who are treated with azathioprine.
Notably, outcomes were comparable between the slow and rapid tapering groups, even with several differences in dosage regimens. One of these differences included starting with a high dose of prednisone in the rapid tapering group; this method is commonly reserved for hospital settings given the possibility of paradoxical worsening of symptoms in the first week.
This trial suggests a more rapid taper in these patients is possible and that further testing may help validate prednisone tapering regimens.
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