Randomized data back EULAR guidelines for mycophenolate mofetil use in AAV
medwireNews: Mycophenolate mofetil (MMF) is noninferior to cyclophosphamide for inducing remission among patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), randomized trial data show.
And although the risk for relapse was higher with MMF, Lorraine Harper (University of Birmingham, UK) and colleagues say that it “represents an alternative to [cyclophosphamide] for remission induction in AAV.”
They add that the study “provides further evidence to support the EULAR guidelines on management of AAV,” which recommend the use of MMF in combination with glucocorticoids for non-organ-threatening cases of the condition.
Of the 66 adults and four children with newly diagnosed AAV who were randomly assigned to treatment with MMF at a dose of 2–3 g/day for adults and a body surface area-based regimen for children, 67% (including one child) met the primary study endpoint of remission by 6 months while adhering to their concurrent glucocorticoid tapering regimen.
This was statistically noninferior to the rate of 61% (also including one child) among the 66 adults and four children randomly assigned to treatment with pulsed cyclophosphamide 15 mg/kg every 2–3 weeks.
Time to remission was also similar between the groups, at 91 and 87 days, respectively, but there were significantly higher rates of relapse following remission in the MMF group than in the cyclophosphamide group, at 33% versus 19%.
A post-hoc analysis showed that the higher relapse rate with MMF was driven by significantly more relapses among patients with PR3-ANCA (48 vs 24% with cyclophosphamide), with no difference observed between the two treatments for patients with MPO-ANCA (15 vs 12%).
Writing in the Annals of the Rheumatic Diseases, Harper and co-authors suggest the higher relapse risk associated with MMF “may be acceptable to avoid the potential adverse effects of [cyclophosphamide] particularly when the baseline risk of relapse is low (eg, in patients who are MPO-ANCA positive) or if rituximab is unavailable.”
The advantages of MMF over cyclophosphamide include fertility preservation for younger patients and the possibility of lower malignancy rates in elderly populations at greatest risk, they explain.
Serious adverse event rates were similar between the two groups, at 50% and 40% for MMF and cyclophosphamide, respectively, with 26% and 17% of each group experiencing serious infections.
The researchers note that since the trial began, rituximab has become a common alternative to cyclophosphamide induction therapy, which may call into question the use of MMF in this setting.
However, they add that rituximab is expensive and subject to limitations in its use in some countries, meaning that “[a]lternative effective low-cost induction therapies may be required in some cases.”
Harper et al conclude: “With increasing remission induction treatment options for AAV, stratified treatment approaches are indicated in order to optimise long-term outcomes.”
By Laura Cowen
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