Follow-up of phase I trial of adalimumab and rosiglitazone in FSGS: III. Report of the FONT study group

Abstract

BackgroundPatients with resistant primary focal segmental glomerulosclerosis (FSGS) are at high risk of progression to chronic kidney disease stage V. Antifibrotic agents may slow or halt this process. We present outcomes of follow-up after a Phase I trial of adalimumab and rosiglitazone, antifibrotic drugs tested in the Novel Therapies in Resistant FSGS (FONT) study.Methods21 patients -- 12 males and 9 females, age 16.0 ± 7.5 yr, and estimated GFR (GFRe) 121 ± 56 mL/min/1.73 m2 -- received adalimumab (n = 10), 24 mg/m2 every 14 days or rosiglitazone (n = 11), 3 mg/m2 per day for 16 weeks. The change in GFRe per month prior to entry and after completion of the Phase I trial was compared.Results19 patients completed the 16-week FONT treatment phase. The observation period pre-FONT was 18.3 ± 10.2 months and 16.1 ± 5.7 months after the study. A similar percentage of patients, 71% and 56%, in the rosiglitazone and adalimumab cohorts, respectively, had stabilization in GFRe, defined as a reduced negative slope of the line plotting GFRe versus time without requiring renal replacement therapy after completion of the FONT treatment period (P = 0.63).ConclusionNearly 50% of patients with resistant FSGS who receive novel antifibrotic agents may have a legacy effect with delayed deterioration in kidney function after completion of therapy. Based on this proof-of-concept preliminary study, we recommend long-term follow-up of patients enrolled in clinical trials to ascertain a more comprehensive assessment of the efficacy of experimental treatments.

Circulating Permeability Factors in Idiopathic Nephrotic Syndrome and Focal Segmental Glomerulosclerosis

“…The study is ongoing and analysis has not yet been reported. A multicenter phase I trial of rosiglitazone (63,64) and of adalimumab has also been completed (64,65). The salutary responses in some patients and the low incidence of adverse effects support the potential clinical utility of such agents.…”

Mitochondrial dysfunction in the pathophysiology of renal diseases

“…A phase I study of rosiglitazone in patients with primary FSGS showed that it was safe and well tolerated (70). The mean 18-mo follow-up in another phase I trial of rosiglitazone suggested that nearly 50% of patients had a legacy effect with delayed deterioration in kidney function (107). The ongoing phase II/III trial will further ascertain the efficacy of TZDs in nephropathy.…”

Glomerular Diseases

“…In a phase I trial, patients treated with adalimumab (a TNF inhibitor with antifibrotic properties) and rosiglitazone (an antidiabetic medication but with antifibrotic properties) showed improvement in GFR over time; however, this study was only 16 weeks and efficacy remains untested (45).…”