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

Peyser A, Machardy N, Tarapore F, Machardy J, Powell L, Gipson DS, Savin V, Pan C, Kump T, Vento S, Trachtman H - BMC Nephrol (2010)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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.

ABSTRACT

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).

Conclusion: 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.

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This graph illustrates the estimated GFR versus time (in months) prior to and after completion of the 6-month FONT Treatment Period in patients assigned to adalimumab.
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Figure 2: This graph illustrates the estimated GFR versus time (in months) prior to and after completion of the 6-month FONT Treatment Period in patients assigned to adalimumab.

Mentions: During the observation period after completion of the FONT study, 5 patients progressed to CKD stage V - 4 enrolled to the rosiglitazone arm and 1 in the adalimumab group (P = 0.31). Figures 1 and 2 illustrate the linear plots of GFRe versus months of observation prior to enrollment in the FONT Phase I trial and after completion of the 16-week experimental Treatment Period for each patient assigned to rosiglitazone (Figure 1) or to adalimumab (Figure 2). The change in the slope of the line relating GFRe versus time during the period before and after the FONT study period is summarized in Table 2. There was no significant difference in the change in this value between the group of patients treated with adalimumab compared to those who received rosiglitazone (P = 0.74). The impact of the two FONT therapies on the rate of change in kidney function was not significantly altered if the results of the 5 patients who progressed to CKD Stage V were excluded from the analysis, 1.72 ± 4.10 and 0.49 ± 6.02 ml/min/1.73 m2/month in the rosiglitazone and adalimumab groups, respectively (P = 0.65). Overall, among those patients who did not progress to CKD Stage V requiring initiation of renal replacement therapy, a similar percentage in each cohort 5/9(56%) versus 5/7 (71%) displayed stabilization in GFRe therapy during the observation period after completion of the FONT study, based on a less steep slope of the GFRe versus time line (P = 0.68).


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

Peyser A, Machardy N, Tarapore F, Machardy J, Powell L, Gipson DS, Savin V, Pan C, Kump T, Vento S, Trachtman H - BMC Nephrol (2010)

This graph illustrates the estimated GFR versus time (in months) prior to and after completion of the 6-month FONT Treatment Period in patients assigned to adalimumab.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2823728&req=5

Figure 2: This graph illustrates the estimated GFR versus time (in months) prior to and after completion of the 6-month FONT Treatment Period in patients assigned to adalimumab.
Mentions: During the observation period after completion of the FONT study, 5 patients progressed to CKD stage V - 4 enrolled to the rosiglitazone arm and 1 in the adalimumab group (P = 0.31). Figures 1 and 2 illustrate the linear plots of GFRe versus months of observation prior to enrollment in the FONT Phase I trial and after completion of the 16-week experimental Treatment Period for each patient assigned to rosiglitazone (Figure 1) or to adalimumab (Figure 2). The change in the slope of the line relating GFRe versus time during the period before and after the FONT study period is summarized in Table 2. There was no significant difference in the change in this value between the group of patients treated with adalimumab compared to those who received rosiglitazone (P = 0.74). The impact of the two FONT therapies on the rate of change in kidney function was not significantly altered if the results of the 5 patients who progressed to CKD Stage V were excluded from the analysis, 1.72 ± 4.10 and 0.49 ± 6.02 ml/min/1.73 m2/month in the rosiglitazone and adalimumab groups, respectively (P = 0.65). Overall, among those patients who did not progress to CKD Stage V requiring initiation of renal replacement therapy, a similar percentage in each cohort 5/9(56%) versus 5/7 (71%) displayed stabilization in GFRe therapy during the observation period after completion of the FONT study, based on a less steep slope of the GFRe versus time line (P = 0.68).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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.

ABSTRACT

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).

Conclusion: 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.

Show MeSH
Related in: MedlinePlus