What is your role in the study?
Dr. Cattran: Dr. Fernando Fervenza of the Mayo Clinic [Rochester, Minn.] and I are the two principal investigators of this trial. We are testing in an open-label, randomized controlled trial whether rituximab is non-inferior to the calcineurin inhibitor cyclosporine in inducing and maintaining a remission of the nephrotic syndrome in patients with idiopathic membranous nephropathy.
What is the current gold standard for membranous nephropathy treatment and/or management?
Dr. Cattran: The KDIGO [Kidney Disease: Improving Global Outcomes] guideline in glomerulonephritis was published as a supplement in Kidney International Supplements [2012;2(2); http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO-GN-Guideline.pdf].
The number-one recommendation for treatment of MGN in this guideline was the use of a six-month cycling routine alternating a cytotoxic drug (cyclophosphamide or chlorambucil) with corticosteroid therapy. In large part this was number one because the evidence at 10-year follow-up is better defined using this therapy than it is with the other number-one recommendation, a calcineurin inhibitor such as cyclosporine.
The latter is the more commonly used first-line therapy in the United States and Canada, whereas the former routine is favored in Europe. This preference in the United States and Canada is largely because of the concerns about both the short- and long-term side-effect profile of the cytotoxic agents as well as the rather high-dose steroid exposure, especially considering the increasing age of presentation of the MGN population.
Why are you evaluating the effectiveness of rituximab in particular?
Dr. Cattran: Our experience to date suggests that the initial response based on randomized controlled trials of the calcineurin inhibitors and several small but non-randomized pilot studies of rituximab have similar response rates in terms of proteinuria in MGN patients.
However, there are certain advantages of rituximab in terms of adherence (given as an intravenous infusion) and side-effect profile that are distinctly different from cyclosporine. In addition, preliminary evidence suggests that the maintenance of remission might be significantly more prolonged with rituximab versus the calcineurin inhibitor, which would be a major advance in the management of these patients.
So the findings could change the landscape of membranous nephropathy therapy?
Dr. Cattran: Yes; we firmly believe that this could change the treatment landscape of idiopathic membranous nephropathy. We will be combining the therapeutic testing of these two agents with certain basic scientific studies, including serial measurement of the autoantibody.
We consider that if our theory is correct, rituximab could become the number-one drug therapy for this disease process given its advantages listed above, at least in patients who are at high risk of progression to renal failure (the only ones who are eligible for our study).
When can we expect the study to yield results?
Dr. Cattran: Enrollment has begun; we have a target of recruiting 126 idiopathic MGN patients. To be eligible, all patients must have high-grade proteinuria. The total study length is five years, with an expected enrollment period of 30 months. This will allow 12 months of treatment and 12 months of follow-up for the last patient randomized and six months for analysis of the study data collected.