Mycophenolate mofetil (MMF) may be a safe and effective alternative to the standard induction therapy cyclophosphamide in certain ANCA-associated vasculitis (AAV) patients, a review study reports.
Based on the data, researchers recommend that MMF be used in patients with autoantibodies against myeloperoxidase (MPO), non-life-threatening disease, and those who have valid reasons to avoid cyclophosphamide.
The study, “Efficacy of mycophenolate mofetil as a remission induction therapy in antineutrophil cytoplasmic antibody: associated vasculitis—a meta-analysis,” was published in the journal Rheumatic and Musculoskeletal Diseases Open.
AAV is a group of autoimmune diseases caused by the production of anti-neutrophil cytoplasmic autoantibodies (ANCAs), which mainly target one of two proteins — MPO and proteinase 3 (PR3) — in neutrophils, a type of immune cell. These immune cells are wrongly activated and start destroying blood vessels, leading to swelling in different tissues and organs.
The effectiveness of intensive immunosuppressive therapies, such as cyclophosphamide and, more recently, rituximab, in inducing remission in patients with organ- or life-threatening AAV is well-established and they are recommended as induction therapies.
However, cyclophosphamide is a type of chemotherapy associated with a high rate of adverse side effects — including infection, low counts of white blood cells, infertility, and cancer — and rituximab is very expensive and often linked to a higher risk of infection.
Therefore, the development or identification of less toxic induction therapies is an unmet need of this patient population.
MMF, an oral immunosuppressive therapy sold by Genentech as CellCept, has been used since the 1990s following kidney transplants, and more recently, for the treatment of autoimmune diseases, including lupus.
Increasing evidence shows that MMF, which is not associated with an increased risk of infertility or cancer, also is effective in treating AAV patients.
While MMF was shown to have equivalent or superior effectiveness and less side effects than cyclophosphamide in people with lupus, its potential equivalence or superiority in AAV patients remains unclear.
Researchers in Japan now set out to assess whether MMF may be an alternative therapy to cyclophosphamide in AAV by systematically reviewing published data from randomized controlled trials comparing the two approaches.
They searched for relevant studies containing at least six-month remission rates data in three databases, with final searches being conducted in September 2019.
From a total of 508 studies initially considered, four (two in Europe and two in China) met the intended criteria and were included in the meta-analysis, covering a total of 300 AAV patients.
The studies included patients with only the granulomatosis with polyangiitis or microscopic polyangiitis types of AAV, and excluded those with life-threatening AAV.
About half of all patients were men (162), their ages ranged from 49 to 61, and they were followed for six months (two trials), 18 months (one trial), or four years (one trial). Kidney involvement was present in 75% to 100% of them, and lung involvement in 46% to 61%.
Age, gender, disease activity, and organ involvement were similar between the studies, while other factors, including the type of autoantibodies produced, differed, providing considerable heterogeneity (diversity) among them.
Most patients (80%–100%) in the Chinese studies were positive for MPO autoantibodies, whereas the presence of autoantibodies against PR3 prevailed among those participating in the European trials (59.1%–89.3%).
These autoantibody differences were not surprising, as ANCA profiles in AAV patients vary between Western and Asian countries, with “PR3-ANCA positivity [being] more common in Western countries and MPO-ANCA positivity in Asian ones,” the researchers wrote.
MMF’s dose varied from 1 to 2 g per day, while cyclophosphamide was given orally or directly into the bloodstream in variable regimens.
Data showed that MMF and cyclophosphamide treatments resulted in similar six-month remission rates, proportions of patients without ANCAs (a predictor of remission) at six months, and relapse rates throughout follow-up.
Notably, there was an association between the presence of MPO-ANCAs and higher six-month remission rates, suggesting that AAV patients who are positive for MPO autoantibodies may respond better to MMF than those with autoantibodies against PR3.
The researchers noted that this is consistent with previous data showing that people with MPO-ANCA-positive AAV are less likely to relapse than those with PR3-ANCA-positive AAV.
The therapies also showed similar safety profiles, resulting in equivalent rates of mortality, infection, low levels of white blood cells, kidney failure, and cancer. Infertility rates could not be assessed in this meta-analysis.
These safety findings highlighted the need to closely monitor infection in AAV patients treated with either therapy and to evaluate the long-term cancer occurrence in those treated with MMF in future studies.
“MMF is recommended for patients with certain characteristics (MPO-ANCA-positive AAV, non-life-threatening state and valid reasons to avoid using the conventional drug),” the researchers wrote, advising caution when using MMF in AAV patients with PR3 autoantibodies.
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June 04, 2020 at 07:00PM
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Mycophenolate Mofetil May Be Alternative to Cyclophosphamide in Certain AAV Patients - ANCA Vasculitis News
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