Two controlled trials have compared belatacept, a new immunosuppressive monoclonal antibody, with ciclosporin in patients who have undergone kidney transplantation.

Belatacept is an immunosuppressive drug that reduces T-cell activation, and in phase 2 trials it was shown to be effective as first-line maintenance immunosupression in controlling rejection after renal transplantation. Two larger phase three trials have now been published.

The first trial, termed BENEFIT, assessed two belatacept regimens (termed more intensive, MI, and less intensive, LI) against standard ciclosporin therapy in patients receiving living or cadaver donor kidney transplants. They were randomised to one of the maintenance regimens after standard initial therapy. Three 12-month co-primary outcomes were used: patient/graft survival, a composite renal impairment endpoint (percent with a measured glomerular filtration rate (mGFR) <60 mL/min/1.73 m2 at Month 12 or a decrease in mGFR ≥10 mL/min/1.73 m2 Month 3–Month 12), and the incidence of acute rejection.

A total of 686 patients were randomised, and at 12 months both belatacept regimens had similar patient/graft survival versus ciclosporin (MI: 95%, LI: 97% and cyclosporine: 93%). Belatacept treatment was associated with superior renal function as measured by the composite renal impairment endpoint (MI: 55%; LI: 54% and ciclosporin: 78%; p ≤ 0.001 MI or LI versus ciclosporin) and by the mGFR (65, 63 and 50 mL/min for MI, LI and ciclosporin; p ≤ 0.001 MI or LI versus ciclosporin).

Patients treated with belatacept had more instances of acute rejection (MI: 22%, LI: 17% and ciclosporin: 7%), and post-transplant lymphoproliferative disorder was more common (belatacept 4 plus 2 after 12 months, ciclosporin 1) and malignancies (9 vs. 1).

The authors of this study conclude that in this study, belatacept was associated with similar graft survival to ciclosporin with better renal function at 12 months.

The second study, termed BENEFIT-EXT, compared belatacept with ciclosporin in extended criteria donors (i.e. older donors and those with health issues that may increase risk of graft failure or dysfunction). Similar treatment regimens and outcomes were used.

In this study, 578 patients were randomised. Results were similar to those of the BENEFIT trial.  Patient/graft survival with belatacept was similar to ciclosporin (86% MI, 89% LI, 85% ciclosporin) at 12 months. Fewer belatacept patients reached the composite renal impairment endpoint versus ciclosporin (71% MI, 77% LI, 85% ciclosporin; p = 0.002 MI vs. ciclosporin; p = 0.06 LI vs. ciclosporin).

The rate of malignancies was similar in the study groups, however post-transplant lymphoproliferative disorder was more common in the belatacept group (belatacept 3 plus 2 after 12 months, ciclosporin 0).

In this study also, the authors conclude that graft survival with belatacept was similar to that with ciclosporin, however renal function at 12 months was better.

An accompanying editorial comments on the studies. The author concludes that if the problems with belatacept and similar drugs can be managed acceptably, the results may ‘herald the start of a new era in immunosuppression’. He comments that the transplant community will be enthusiastic for the potential of these new therapies, but must be vigilant for the unpleasant surprises that they may present.

[Editor’s note: belatacept is not yet licensed anywhere in the world – a licensing submission for the EU is expected later this year.]