Belatacept-based immunosuppression with simultaneous calcineurin inhibitor avoidance and early corticosteroid withdrawal: A prospective, randomized multicenter trial.
Ervin Steve WoodleDixon B KaufmanAdele Rike ShieldsJohn LeoneArthur J MatasAlexander WisemanPatricia West-ThielkeTing SaEileen C KingRaymond T Chungnull nullPublished in: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (2020)
Simultaneous calcineurin inhibitor avoidance (CNIA) and early corticosteroid withdrawal (ESW) have not been achieved primarily due to excessive acute rejection. This trial compared 2 belatacept-based CNIA/ESW regimens with a tacrolimus-based ESW regimen. Kidney transplant recipients were randomized to receive alemtuzumab/belatacept, rabbit anti-thymocyte globulin (rATG)/belatacept, or rATG/tacrolimus. The combinatorial primary endpoint consisted of patient death, renal allograft loss, or a Modification of Diet in Renal Disease-calculated eGFR of <45 mL/min/1.73 m2 at 12 months. Results are reported by treatment group (alemtuzumab/belatacept, rATG/belatacept, and rATG/tacrolimus). Superiority was not observed at 1 year for the primary endpoint (9/107 [8.4%], 15/104 [14.4%], and 14/105 [13.3%], respectively; P = NS) for either belatacept-based regimen. Differences were not observed for secondary endpoints (death, death-censored graft loss, or estimated glomerular filtration rates < 45 mL/min/1.73 m2 ). Differences were observed in biopsy-proved acute cellular rejection (10.3%, 18.3%, and 1.9%, respectively) (P < .001), but not in antibody-mediated rejection, mixed acute rejection, or de novo donor-specific anti-HLA antibodies. Neurologic and electrolyte abnormality adverse events were less frequent under belatacept. Belatacept-based CNIA/ESW regimens did not prove to be superior for the primary or secondary endpoints. Belatacept-treated patients demonstrated an increase in biopsy-proved acute cellular rejection and reduced neurologic and metabolic adverse events. These results demonstrate that simultaneous CNIA/ESW is feasible without excessive acute rejection.
Keyphrases
- liver failure
- respiratory failure
- drug induced
- aortic dissection
- phase iii
- clinical trial
- phase ii
- physical activity
- study protocol
- open label
- hepatitis b virus
- double blind
- end stage renal disease
- newly diagnosed
- ejection fraction
- intensive care unit
- ultrasound guided
- body mass index
- cross sectional
- case report
- zika virus
- endothelial cells
- aedes aegypti