title: Complete and Partial Remission as Surrogate End Points in Membranous Nephropathy.
abstract: Absent a remission of proteinuria, primary membranous nephropathy (MN) can lead to ESRD over many years. Therefore, use of an earlier end point could facilitate the conduct of clinical trials. This manuscript evaluates complete remission (CR) and partial remission (PR) of proteinuria as surrogate end points for a treatment effect on ESRD in patients with primary MN with heavy proteinuria. CR is associated with a low relapse rate and excellent long-term renal survival, and it plausibly reflects remission of the disease process that leads to ESRD. Patients who achieve PR have better renal outcomes than those who do not but may have elevated relapse rates. How long PR must be maintained to yield a benefit on renal outcomes is also unknown. Hence, available data suggest that CR could be used as a surrogate end point in primary MN, whereas PR seems reasonably likely to predict clinical benefit. In the United States, surrogate end points that are reasonably likely to predict clinical benefit can be used as a basis for accelerated approval; treatments approved under this program must verify the clinical benefit in postmarketing trials. Additional analyses of the relationship between treatment effects on CR and PR and subsequent renal outcomes would inform the design of future clinical trials in primary MN.
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland;
authors.forename: Aliza
authors.initials: A
authors.lastname: Thompson
authors.affiliation: Division of Clinical Investigation and Human Physiology, Toronto General Research Institute, Toronto General Hospital, Toronto, Ontario, Canada; and.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Cattran
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland;
authors.forename: Melanie
authors.initials: M
authors.lastname: Blank
authors.affiliation: University of North Carolina Kidney Center, University of North Carolina, Chapel Hill, North Carolina patrick_nachman@med.unc.edu.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Nachman
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine*; D018450:Disease Progression; D023381:Endpoint Determination; D005919:Glomerular Filtration Rate; D015433:Glomerulonephritis, Membranous / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000517:prevention & control*; D011507:Proteinuria / Q000209:etiology / Q000652:urine*; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers
keywords: glomerular disease; membranous nephropathy; nephrotic syndrome; outcomes; surrogate outcomes