NULOJIX (bélatacept) - Prévention du rejet de greffon rénal adultes

 Key points

Positive opinion for reimbursement in the prevention of graft rejection, in combination with corticosteroids and mycophenolic acid, in adult EBV+ kidney transplant patients in the context of conversion from a treatment including a CNI at least 6 months post-tranplant.

Therapeutic improvement?

No progress in the therapeutic strategy for the prevention of graft rejection in adult kidney transplant recipients, converting from treatment with a calcineurin inhibitor (CNI) at least 6 months post-transplant.

Role in therapeutic strategy?

Immunosuppression protocols are based on two phases of treatment:

• an initial "induction" phase with stronger immunosuppression, based on the administration of depleting or non-depleting monoclonal (anti-CD3) or polyclonal (anti-lymphocyte serum) antibodies (basiliximab or daclizumab)
• a maintenance phase based on five therapeutic classes, often combined:
  • corticosteroids;
  • anticalcineurins: cyclosporin and preferably tacrolimus;
  • antimetabolics: azathioprine, mycophenolate mofetil and mycophenolic acid;
  • mTOR inhibitors: sirolimus and everolimus;
  • the T-cell co-stimulation inhibitor: belatacept.

The maintenance phase of immunosuppression usually involves a combination of two or three immunosuppressive drugs, which may be modified according to the clinical situation. The most commonly used protocol combines an anticalcineurin (preferably tacrolimus) with an antimetabolic agent.

Immunosuppression protocols are prescribed according to numerous immunological parameters, including the initial compatibility between the host and the graft, the occurrence of rejection or infection, and the recipient's age.

According to the 2021 European Association of Urology recommendations, when discontinuation of the current anticalcineurin treatment is deemed necessary by the practitioner, different treatment options may be considered for conversion, depending on the clinical situation justifying the discontinuation: a different anticalcineurin agent, mTOR inhibitors, antimetabolics or belatacept.

NULOJIX (belatacept) is the only immunosuppressant available as a dilutable solution for intravenous infusion (monthly infusion).

Role of the medicinal product

Based on the results observed in studies IM103010 and IM103016, although of low methodological quality, the Committee considers that NULOJIX (belatacept), in combination with corticosteroids and mycophenolic acid (MPA), is a first-line option for the prevention of graft rejection in adult kidney transplant patients in conversion to a maintenance therapy with a CNI, at least 6 months post-transplant.

In the absence of comparative data, the role of NULOJIX (belatacept) in relation to other treatment options that may be considered for conversion from a CNI, in accordance with the latest European recommendations, cannot be determined. 

Given the data suggesting less renal toxicity in patients who have converted to belatacept compared to patients continuing with a CNI, as already observed in studies of de novo transplant patients treated with belatacept compared to ciclosporin, NULOJIX (belatacept) may be of particular interest in patients with nephrotoxicity. 

A higher risk of acute rejection was also observed after conversion to belatacept, particularly at the start of treatment, bearing in mind that patients at high immunological risk were excluded from the studies. In line with the SCP, the Committee underlines that more frequent monitoring for acute rejection is therefore recommended for at least 6 months after conversion to belatacept, and that conversion in patients at high immunological risk should only be considered if the potential benefits are considered to outweigh the risks.

As a reminder, belatacept is contraindicated in transplant patients who are seronegative or of unknown serostatus for Epstein-Barr virus (EBV) due to the risk of developing a post-transplant lymphoproliferative syndrome (PTLS).