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


METHODS
21 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.


RESULTS
19 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).


CONCLUSIONS
Nearly 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.
Peyser
Alexandra
A
Department of Pediatrics, Division of Nephrology, Schneider Children's Hospital of North Shore-LIJ Health System, 269-01 76th Avenue, New Hyde Park, NY 11040, USA.
Machardy
Nathaniel
N
Tarapore
Freya
F
Machardy
Jacqueline
J
Powell
Leslie
L
Gipson
Debbie S
DS
Savin
Virginia
V
Pan
Cynthia
C
Kump
Theresa
T
Vento
Suzanne
S
Trachtman
Howard
H
D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000068879:Adalimumab