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Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial.
Am J Kidney Dis. 2017 May; 69(5):587-594.AJ

Abstract

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+Show Affiliations

University of Barcelona, IDIBELL, Barcelona, Spain. Electronic address: jgrinyo@ub.edu.Instituto de Nefrologia, Buenos Aires, Argentina.Instituto Nacional de Ciencias Medicas y Nutricion, Tlalpan, Mexico.Balboa Institute of Transplantation, San Diego, CA.Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.Lakeshore Hospital, Kochi, India.UCSF Transplant Service, San Francisco, CA.Bristol-Myers Squibb, Princeton, NJ.Toulouse University Hospital, Toulouse, France.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

27889299

Citation

Grinyó, Josep M., et al. "Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 69, no. 5, 2017, pp. 587-594.
Grinyó JM, Del Carmen Rial M, Alberu J, et al. Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial. Am J Kidney Dis. 2017;69(5):587-594.
Grinyó, J. M., Del Carmen Rial, M., Alberu, J., Steinberg, S. M., Manfro, R. C., Nainan, G., Vincenti, F., Jones-Burton, C., & Kamar, N. (2017). Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 69(5), 587-594. https://doi.org/10.1053/j.ajkd.2016.09.021
Grinyó JM, et al. Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial. Am J Kidney Dis. 2017;69(5):587-594. PubMed PMID: 27889299.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial. AU - Grinyó,Josep M, AU - Del Carmen Rial,Maria, AU - Alberu,Josefina, AU - Steinberg,Steven M, AU - Manfro,Roberto C, AU - Nainan,Georgy, AU - Vincenti,Flavio, AU - Jones-Burton,Charlotte, AU - Kamar,Nassim, Y1 - 2016/11/23/ PY - 2016/01/13/received PY - 2016/09/26/accepted PY - 2016/11/28/pubmed PY - 2017/8/2/medline PY - 2016/11/28/entrez KW - Kidney transplant KW - acute rejection KW - adverse events KW - belatacept KW - calcineurin inhibitor (CNI) KW - conversion study KW - graft loss KW - immunosuppression KW - kidney function KW - phase 2 randomized controlled trial KW - renal transplantation KW - safety KW - switch SP - 587 EP - 594 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am. J. Kidney Dis. VL - 69 IS - 5 N2 - 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. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/27889299/Safety_and_Efficacy_Outcomes_3_Years_After_Switching_to_Belatacept_From_a_Calcineurin_Inhibitor_in_Kidney_Transplant_Recipients:_Results_From_a_Phase_2_Randomized_Trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(16)30572-8 DB - PRIME DP - Unbound Medicine ER -