This work was published on 27 June 2016 in the Journal of the American Society of Nephrology.
Membranous glomerulonephritis is a rare autoimmune disease (one new case recorded per year per 100,000 inhabitants), in most cases caused by antibodies directed against a protein (PLA2R) located in the renal filter (the glomerulus). The immunosuppressive treatments – aimed at attenuating this immune reaction of the body – that have been used until now have shown some efficacy, associated, however, with considerable toxicity: risks of infection, fertility problems, subsequent development of cancer or impaired renal function.
Rituximab is a monoclonal antibody specifically directed against the B lymphocytes that produce the toxic antibodies. Until now, its safety and efficacy had not been demonstrated.
In this context, Prof. Pierre Ronco and Dr Karine Dahan conducted a study in 80 patients with a severe form of membranous glomerulonephritis at Tenon Hospital AP-HP. The patients were enrolled from January 2012 to July 2014 in 31 nephrology departments throughout France, including 9 departments of Paris public hospitals (AP-HP) , with annual follow-up for two years.
This randomised study made it possible to compare the efficacy of the standard treatment, known as “antiproteinuric,” with the same treatment combined with 2 intravenous infusions of rituximab (375 mg/m2) given at a one-week interval. Patients were observed for the occurrence of immunological remission (disappearance of antibodies), clinical remission (reduction or disappearance of proteinuria) and adverse effects of the treatment.
The percentage of remission was similar to that obtained with other immunosuppressive treatments, but with a much lower therapeutic risk, since the number of adverse events was the same in both treatment groups (with or without rituximab).
“This study contributes a very important element to the debate surrounding immunosuppressive treatments in membranous glomerulonephritis,” explains Prof. Pierre Ronco.
“In clinical terms, it favours the use of rituximab as a first-line treatment in severe forms, with very regular monitoring of the level of anti-PLA2R antibodies in these patients.”
This study will provide a basis for other protocols aimed at increasing the percentage of clinical and immunological remission without increasing the rate of adverse effects. It is likely that some patients did not respond to the treatment because the rituximab leaked into the urine. These protocols will therefore include the use of higher or more frequent doses, and further IV infusions in patients who maintain high antibody levels.
Des scientifiques du Trinity College de Dublin, de l’Inserm, d’Université Paris Cité et de l’AP-HP au sein de l'Institut Imagine à l'hôpital Necker, à Paris, viennent de découvrir un....