10 Yearsʼ Experience with Belatacept (Nulojix®)

Abstract

Introduction: Belatacept was approved in 2011 as novel immunosuppressive agent for prevention of acute rejection in adult patients undergoing kidney transplantation on the basis of two open-label, randomized, multicenter, controlled phase 3 studies. From these studies meanwhile 3 years' data are published but longer term results are of particular interest. Patients and methods: From March 2001 November 2002 a total of 218 patients were enrolled in an open-label, randomized, multicenter, controlled phase 2 study. Patients were randomly assigned to 3 treatment groups: “less intensive” belatacept, “more intensive” belatacept, and standard cyclosporine A (Sandimun Optoral/ Neoral®). 5 year data from this phase II study were published. In our department 20 patients (15 receiving belatacept, 5 cyclosporine A) were included, 6 patients meanwhile completed the long term extension of the study. Five are still receiving belatacept. We analyzed reasons for drop out, renal function, acute rejection, development of malignancies and survival. Results: From a total of 14 drop outs most occurred in the first month after transplant: 8 (53%) in the belatacept group and 2 (40%) in the cyclosporine group. From year 5 on only 1 further drop out was observed. Reasons for early drop out were rejections in 4 patients (all belatacept), in 3 patients CMV infections (2 cyclosporine, 1 belatacept), in 2 patients side effects (gastrointestinal disorder and agranulocytosis) and in 1 patient withdrawal of consent. Graft function of the belatacept patients declined from a median clearance of 102ml/min at year 1 to 59ml/min (range 44-79ml/min) at year 10. The 3 patients of the cyclosporine group, which completed the first year, had a median clearance of 58ml/min (range 49-95ml/min). Only the patient with the best graft function completed the long term extension. Clearance declined over the time from 95ml/ min to 59ml/min. Rejections were observed in 6 patients (40%) receiving belatacept and in 2 patients (40%) receiving cyclosporine. Overall, 3 of the 20 patients developed malignancies. Two male patients suffered from bronchial cancer (both smokers; one 2 years after transplantation and withdrawn IC on day 5, the other 8 years after transplantation and under treatment of belatacept), one female patient developed a cervical intraepithelial neoplasia 7 years after transplantation and under treatment of belatacept. Five of the 20 patients died. Four of them after or while receiving belatacept at month 18 after transplantation (sepsis due to pleural empyema after mitral valve replacement), year 2 after transplantation (one patient with unknown reason; one patient due to bronchial cancer, withdrawn IC with switch to cyclosporine A on day 5) and year 8 after transplantation due to bronchial cancer. The patient from the cyclosporine A group died 8 years after transplantation due to a aortic valve stenosis. Conclusion: This is the first report on long term use of Belatacept. Regarding our Patients Belatacept seems to be effective and safe in renal transplant patients. No graft loss due to chronic allograft nephropathy was observed; i.v. administration was well tolerated with less side effects and was well accepted in most patients.