Josep M Grinyó1, Maria Del Carmen Rial2, Josefina Alberu3, Steven M Steinberg4, Roberto C Manfro5, Georgy Nainan6, Flavio Vincenti7, Charlotte Jones-Burton8, Nassim Kamar9. 1. University of Barcelona, IDIBELL, Barcelona, Spain. Electronic address: jgrinyo@ub.edu. 2. Instituto de Nefrologia, Buenos Aires, Argentina. 3. Instituto Nacional de Ciencias Medicas y Nutricion, Tlalpan, Mexico. 4. Balboa Institute of Transplantation, San Diego, CA. 5. Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil. 6. Lakeshore Hospital, Kochi, India. 7. UCSF Transplant Service, San Francisco, CA. 8. Bristol-Myers Squibb, Princeton, NJ. 9. Toulouse University Hospital, Toulouse, France.
Abstract
BACKGROUND: In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from acalcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss. STUDY DESIGN: 36-month follow-up of the intention-to-treat population. SETTING & PARTICIPANTS: CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [eGFR], 35-75mL/min/1.73m2). INTERVENTIONS: At 6 to 36 months posttransplantation, patients were randomly assigned to switch to belatacept-based immunosuppression (n=84) or continue CNI-based therapy (n=89). OUTCOMES: Safety was the primary outcome. eGFR, acute rejection, transplant loss, and death were also assessed. MEASUREMENTS: Treatment exposure-adjusted incidence rates for safety, repeated-measures modeling for eGFR, Kaplan-Meier analyses for efficacy. RESULTS:Serious adverse events occurred in 33 (39%) belatacept-treated patients and 36 (40%) patients in the CNI group. Treatment exposure-adjusted incidence rates for serious infections (belatacept vs CNI, 10.21 vs 9.31 per 100 person-years) and malignancies (3.01 vs 3.41 per 100 person-years) were similar. More patients in the belatacept versus CNI group had any-grade viral infections (14.60 vs 11.00 per 100 person-years). No posttransplantation lymphoproliferative disorder was reported. Belatacept-treated patients had a significantly greater estimated gain in mean eGFR (1.90 vs 0.07mL/min/1.73m2 per year; P for time-by-treatment interaction effect = 0.01). The probability of acute rejection was not significantly different for belatacept (8.38% vs 3.60%; HR, 2.50 [95% CI, 0.65-9.65; P=0.2). HR for the comparison of belatacept to the CNI group for time to death or transplant loss was 1.00 (95% CI, 0.14-7.07; P=0.9). LIMITATIONS: Exploratory post hoc analysis with a small sample size. CONCLUSIONS: Switching patients from a CNI to belatacept may represent a safe approach to immunosuppression and is being further explored in an ongoing phase 3b trial.
RCT Entities:
BACKGROUND: In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss. STUDY DESIGN: 36-month follow-up of the intention-to-treat population. SETTING & PARTICIPANTS: CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [eGFR], 35-75mL/min/1.73m2). INTERVENTIONS: At 6 to 36 months posttransplantation, patients were randomly assigned to switch to belatacept-based immunosuppression (n=84) or continue CNI-based therapy (n=89). OUTCOMES: Safety was the primary outcome. eGFR, acute rejection, transplant loss, and death were also assessed. MEASUREMENTS: Treatment exposure-adjusted incidence rates for safety, repeated-measures modeling for eGFR, Kaplan-Meier analyses for efficacy. RESULTS: Serious adverse events occurred in 33 (39%) belatacept-treated patients and 36 (40%) patients in the CNI group. Treatment exposure-adjusted incidence rates for serious infections (belatacept vs CNI, 10.21 vs 9.31 per 100 person-years) and malignancies (3.01 vs 3.41 per 100 person-years) were similar. More patients in the belatacept versus CNI group had any-grade viral infections (14.60 vs 11.00 per 100 person-years). No posttransplantation lymphoproliferative disorder was reported. Belatacept-treated patients had a significantly greater estimated gain in mean eGFR (1.90 vs 0.07mL/min/1.73m2 per year; P for time-by-treatment interaction effect = 0.01). The probability of acute rejection was not significantly different for belatacept (8.38% vs 3.60%; HR, 2.50 [95% CI, 0.65-9.65; P=0.2). HR for the comparison of belatacept to the CNI group for time to death or transplant loss was 1.00 (95% CI, 0.14-7.07; P=0.9). LIMITATIONS: Exploratory post hoc analysis with a small sample size. CONCLUSIONS: Switching patients from a CNI to belatacept may represent a safe approach to immunosuppression and is being further explored in an ongoing phase 3b trial.
Authors: Klemens Budde; Rohini Prashar; Hermann Haller; María Rial; Nassim Kamar; Avinash Agarwal; Johan de Fijter; Lionel Rostaing; Stefan Berger; Arjang Djamali; Nicolae Leca; Lisa Allamassey; Sheng Gao; Martin Polinsky; Flavio Vincenti Journal: J Am Soc Nephrol Date: 2021-10-27 Impact factor: 10.121
Authors: Anne Bozon; Guillaume Jeantet; Benjamin Rivière; Natalie Funakoshi; Gaspard Dufour; Roman Combes; Jean-Christophe Valats; Sylvie Delmas; Jean Emmanuel Serre; Michael Bismuth; Jeanne Ramos; Moglie Le Quintrec; Pierre Blanc; Guillaume Pineton de Chambrun Journal: World J Gastroenterol Date: 2017-12-28 Impact factor: 5.742
Authors: Asha Moudgil; Vikas R Dharnidharka; Daniel I Feig; Barry L Warshaw; Vidya Perera; Bindu Murthy; Mustimbo E Roberts; Martin S Polinsky; Robert B Ettenger Journal: Am J Transplant Date: 2019-01-22 Impact factor: 8.086