medwireNews: Azathioprine and mycophenolate mofetil both achieve significant improvements in quality-of-life (QoL) outcomes for patients with autoimmune myasthenia gravis, reports the prospective cohort PROMISE-MG study.
Pushpa Narayanaswami (Harvard Medical School, Boston, USA) and colleagues enrolled 167 immunosuppressant-naïve patients with myasthenia gravis from 19 academic centers in the USA and Canada between 2018 and 2020.
The patients were treated with either azathioprine or mycophenolate mofetil at a dose and duration decided by their treating clinician.
In all, 78 patients were included in the final analysis, of whom 31 received azathioprine (≥2 mg/kg per day for at least 12 months and median follow-up of 20 months) and 47 received mycophenolate mofetil (≥2 g per day for at least 8 months and median follow-up of 25 months).
The results showed a significant improvement from baseline for both treatment groups on the Myasthenia Gravis-Quality of Life 15-revised (MG-QOL15r) score – the first of two co-primary outcomes. Mean scores decreased by 6.8 points and 10.4 points with azathioprine and mycophenolate mofetil, respectively, from an initial 14 out of a possible 30 points.
A clinically meaningful reduction (CMR) of at least 5 points on the MG-QOL15r was achieved by 57% of patients in the azathioprine group and 81% of those in the mycophenolate group, a nonsignificant difference. But the time it took to achieve this was longer for patients in the azathioprine group, at a median 6.4 months versus 3.4 months for those taking mycophenolate mofetil.
The second of the co-primary outcomes was a composite of clinical improvement on the MG-QOL15r (minimal manifestations or better) and treatment-related adverse events (AEs) of no more than grade 1. This outcome was attained by 28.1% of azathioprine-treated patients and 47.7% of those treated with mycophenolate mofetil, with the difference not statistically significant.
For secondary outcomes, a CMR of at least 3 points from baseline was seen on the MG Composite, the MG Activities of Daily Living, and the MG Manual Muscle Test in a similar proportion of patients receiving azathioprine or mycophenolate mofetil, at a respective 83–84%, 81–89%, and 70–82%.
And of the 10 hospital admissions needed for myasthenia gravis, 16% occurred among patients in the azathioprine group and 11% among those in the mycophenolate mofetil group, a nonsignificant difference.
The researchers note in The Lancet Neurology that there were “no consistent differences in outcomes” between patients who received the recommended doses of azathioprine or mycophenolate mofetil for at least 12 months and those who received lower doses for shorter durations.
However, they note that patients treated with azathioprine were more frequently given lower drug doses and for shorter durations than their peers treated with mycophenolate mofetil, at rates of 77% versus 32%.
This may explain why the proportions of patients achieving the two co-primary outcomes were numerically lower for those taking azathioprine than for those taking mycophenolate mofetil, observe Narayanaswami and colleagues. However, they add that “[d]espite this, more than half of patients treated with azathioprine had CMRs in all outcomes.”
AEs occurred in 32% of patients in the azathioprine group and 19% of those in the mycophenolate mofetil group, with liver toxicity and gastrointestinal disturbances being the most common, each occurring in 15% of patients, respectively. Serious AEs of grade 2 or above were numerically, but not significantly, higher among patients in the azathioprine group, at 55% versus 34%.
The authors conclude that azathioprine and mycophenolate mofetil “are effective at improving quality of life, function, and muscle strength in patients with myasthenia gravis, are relatively safe, and are inexpensive options that are complementary to the new therapies for myasthenia gravis.”
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