Belatacept for simultaneous calcineurin inhibitor and chronic corticosteroid immunosuppression avoidance: Two-year results of a prospective, randomized multicenter trial

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Abstract

BACKGROUND AND OBJECTIVES: Immunosuppressive therapy in kidney transplantation is associated with numerous toxicities. CD28-mediated T-cell costimulation blockade using belatacept may reduce long-term nephrotoxicity, compared with calcineurin inhibitor-based immunosuppression. The efficacy and safety of simultaneous calcineurin inhibitor avoidance and rapid steroid withdrawal were tested in a randomized, prospective, multicenter study.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study reports the 2-year results of a randomized clinical trial of 316 recipients of a new kidney transplant. All kidney transplants were performed using rapid steroid withdrawal immunosuppression. Recipients were randomized in a 1:1:1 ratio to receive belatacept with alemtuzumab induction, belatacept with rabbit anti-thymocyte globulin (rATG) induction, or tacrolimus with rATG induction. The composite end point consisted of death, kidney allograft loss, or an eGFR of <45 ml/min per 1.73 m 2 at 2 years.

RESULTS: The composite end point was observed for 11 of 107 (10%) participants assigned to belatacept/alemtuzumab, 13 of 104 (13%) participants assigned to belatacept/rATG, and 21 of 105 (21%) participants assigned to tacrolimus/rATG (for belatacept/alemtuzumab versus tacrolimus/rATG, P=0.99; for belatacept/rATG versus tacrolimus/rATG, P=0.66). Patient and graft survival rates were similar between all groups. An eGFR of <45 ml/min per 1.73 m 2 was observed for nine of 107 (8%) participants assigned to belatacept/alemtuzuab, eight of 104 (8%) participants assigned to belatacept/rATG, and 20 of 105 (19%) participants assigned to tacrolimus/rATG ( P<0.05 for each belatacept group versus tacrolimus/rATG). Biopsy sample-proven acute rejection was observed for 20 of 107 (19%) participants assigned to belatacept/alemtuzuab, 26 of 104 (25%) participants assigned to belatacept/rATG, and seven of 105 (7%) participants assigned to tacrolimus/rATG (for belatacept/alemtuzumab versus tacrolimus/rATG, P=0.006; for belatacept/rATG versus tacrolimus/rATG, P<0.001). Gastrointestinal and neurologic adverse events were less frequent with belatacept versus calcineurin-based immunosuppression.

CONCLUSIONS: Overall 2-year outcomes were similar when comparing maintenance immunosuppression using belatacept versus tacrolimus, and each protocol involved rapid steroid withdrawal. The incidence of an eGFR of <45 ml/min per 1.73 m 2 was significantly lower with belatacept compared with tacrolimus, but the incidence of biopsy sample-proven acute rejection significantly higher.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Belatacept Early Steroid Withdrawal Trial, NCT01729494.

Original languageEnglish (US)
Pages (from-to)1387-1397
Number of pages11
JournalClinical Journal of the American Society of Nephrology
Volume16
Issue number9
DOIs
StatePublished - Sep 2021

Bibliographical note

Funding Information:
funding from Medeor Pharma and the National Institutes of Health. E.C. King reports having ownership interest in Procter & Gamble Company and STATKING Clinical Services. A. Matas reports receiving research funding from Alexion, Astellas, Bristol-Myers Squibb, CareDx, Shire, and Veloxis; receiving honoraria from Astellas, CareDx, CSL Behring, and Veloxis; serving as a scientific advisor or member of CareDx, CSL Behring, and Jazz Pharma; and having consultancy agreements with Veloxis. P. West-Thielke reports receiving research funding from Bristol-Myers Squibb, CSL Behring, Novartis, and Veloxis Pharmaceuticals; receiving honoraria from Veloxis Pharmaceuticals; and serving on a speakers bureau for Veloxis Pharmaceuticals. A. Wiseman reports serving as a scientific advisorfor, ormember of, American Journal of Transplantation;receiving research funding from Astellas, Bristol-Meyer Squibb, Hookipa, Medeor, and Novartis; having consultancy agreements with CareDx, Hansa, Mallinkrodt, Natera, Novartis, and Veloxis; serving on a speakers bureau for CareDx, Sanofi Genzyme, and Veloxis; and being employed by Centura Transplant. E.S. Woodle reports receiving research funding from Amgen, Bristol-Myers Squibb, Novartis, Sanofi, and Veloxis; having consultancy agreements with, and receiving honoraria from, Novartis and Sanofi; and serving on a speakers bureau for Sanofi. All remaining authors have nothing to disclose.

Funding Information:
This study was supported by Bristol-Meyers Squibb (IM103-167).

Publisher Copyright:
© 2021 by the American Society of Nephrology.

Keywords

  • Immunosuppression
  • Kidney transplantation
  • Transplant outcomes

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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