Every 2-month belatacept maintenance therapy in kidney transplant recipients greater than 1-year posttransplant: A randomized, noninferiority trial
Belatacept results in improved kidney transplant outcomes, but utilization has been limited by logistical barriers related to monthly (q1m) intravenous infusions. Every 2-month (q2m) belatacept has potential to increase utilization, therefore we conducted a randomized noninferiority trial in low immunologic risk renal transplant recipients greater than 1-year posttransplant. Patients on belatacept were randomly assigned to q1m or q2m therapy. The primary objective was a noninferiority comparison of renal function (eGFR) at 12 months with a noninferiority margin (NIM) of 6.0 ml/min/1.73 m2 . One hundred and sixty-six participants were randomized to q1m (n = 82) or q2m (n = 84) belatacept, 163 patients received treatment, and 76 q1m and 77 q2m subjects completed the 12-month study period. Every 2-month belatacept was noninferior to q1m, as the difference in mean eGFR adjusted for baseline renal function did not exceed the NIM. Two-month dosing was safe and well tolerated, with no patient deaths or graft losses. Four rejection episodes and three cases of donor-specific antibodies (DSAs) occurred among q2m subjects; however, only one rejection and one instance of DSA were observed in subjects adherent to the study protocol. Every 2-month belatacept therapy may facilitate long-term utilization of costimulation blockade, but future multicenter studies with long-term follow-up will further elucidate immunologic risk. (ClinicalTrials.gov NCT02560558).
CET Conclusion
| Reviewer: | Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford |
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| Conclusion: | This well-designed study randomised stable, low risk renal transplant recipients > 1 year post-transplant to once-monthly or once every 2 month belatacept. The study was conducted on a non-inferiority basis, and the authors found that 2-monthly belatacept resulted in non-inferior 12-month eGFR supporting less frequent dosing in these patients. There were numerically more acute rejection episodes in the 2-monthly arm, which the authors ascribe to non-adherent behavior. There is the possibility of detection bias – for safety reasons, the patients in the 2-monthly arm had more frequent lab tests for the 4 months after switching regimens. Nonetheless, this perhaps highlights the importance of careful assessment of patient adherence when considering a regimen such as this, as the potential consequence of missed doses will be greater than more frequent dosing. |
Methodological quality
| Jadad score | 3 |
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| Allocation concealment | YES |
| Data analysis | STRICT INTENTION TO TREAT |
Study Details
| Aims: | The aim of this study was to determine whether the administration of belatacept every two months was noninferior to standard monthly dosing in kidney transplant patients with low immunologic risk. |
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| Interventions: | Participants were randomly assigned to receive belatacept therapy every month (q1m) or every two months (q2m). |
| Participants: | 166 renal transplant patients. |
| Outcomes: | The primary endpoint was the assessment of estimated glomerular filtration rate (eGFR) at 12 months. The secondary endpoints included patient death, graft loss, rejection, the incidence of infections, and formation of donor-specific antibodies (DSA). |
| Follow Up: | 1 year |
Metadata
| Funding: | Non-industry funding |
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| Publication type: | Randomized Controlled Trial, Randomised Controlled Trial |
| Trial registration: | ClinicalTrials.gov - NCT02560558 |
| Organ: | Kidney |
| Language: | English |
| Author email: | ibadell@emory.edu |
| MeSH terms: | Abatacept; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Transplant Recipients; 0 (Immunosuppressive Agents); 7D0YB67S97 (Abatacept) |