BENLYSTA (bélimumab) (glomérulonéphrite lupique)

Key points

Favourable opinion for reimbursement only in combination with standard treatment including corticosteroid and immunosuppressive therapy for the treatment of adult patients with histologic class III or IV, associated or otherwise with class V, active lupus nephritis.

Unfavourable opinion for reimbursement in the treatment of pure class V lupus nephritis.

 What therapeutic improvement?

Therapeutic improvement in the treatment of adult patients with histologic class III or IV, associated or otherwise with class V, active lupus nephritis.

Role in the care pathway?

The treatment of lupus nephritis (LN) depends on the histologic type, defined by renal biopsy. The therapeutic strategy recommended by the French national diagnostic and care protocol (PNDS) (2020) is as follows:

• In the majority of cases, classes I, II, IIIC or IVC LN (without activity A) without additional class V, and class VI LN do not require additional specific treatment.
• Class III(A) or IV(A) +/-C +/-class V LNs are the most severe forms. The objective of treatment is to obtain remission of lupus nephritis within 3 to 6 months by induction therapy in addition to background therapy of systemic lupus (synthetic anti-malarial). The objective of maintenance therapy is to prevent renal recurrences.

Induction therapy combines a corticosteroid with immunosuppressive therapy:

As first-line treatment, two drugs are recommended in addition to corticosteroid therapy (IV bolus of 500 to 1,000 mg of methylprednisolone for 3 days, then oral prednisone at a dose of 0.5 to 1 mg/kg/day, with a target of achieving a lower dose after 6 months, tapered by 5 to 10 mg/d):

• mycophenolate mofetil (MMF 2 to 3 g/d, oral route) for 6 months (mycophenolate sodium (MPA) may be used) or
•  intravenous (IV) cyclophosphamide (CYC) at low doses (500 mg every 2 weeks x 6 doses, EURO-LUPUS regimen). High-dose IV CYC (0.5–0.8 g/m² every 4 weeks for 6 months, short NIH regimen) may be considered in patients with more severe renal involvement.

As second-line treatment, if remission is not obtained after 6 months with one of the two immunosuppressive therapies (CYC or MMF), it is recommended to try the other immunosuppressive therapy.

As third-line treatment in refractory patients, rituximab may be recommended, in combination with corticosteroids and/or immunosuppressive therapies, following the opinion of a reference/expert centre or a specialist centre.

Tacrolimus or ciclosporin may be proposed in difficult cases, in combination with corticosteroids +/- MMF.

Maintenance therapy

The recommended maintenance therapy is based on MMF/MPA or azathioprine (AZA), maintained for at least 2 to 3 years, in combination with low-dose prednisone if necessary. It is probably necessary to continue this treatment for well beyond 3 years in patients at high risk of recurrence.

Finally, for class V +/- LN, combined with class IIIC or IVC, few studies have been conducted given how rare these forms are. The PNDS recommendations are based on expert opinions.

Only clinical forms at risk of developing complications require specific treatment (nephrotic syndrome or proteinuria ≥ 2 g/g and/or progression of CKD), combining corticosteroids and immunosuppressive therapies (CYC or ciclosporin A or AZA or MMF).

Role of BENLYSTA (belimumab) in the care pathway:

Considering:

• demonstration of the efficacy of belimumab in adult patients with active lupus nephritis receiving standard therapy including a high-dose corticosteroid plus an immunosuppressive therapy (cyclophosphamide, mycophenolate mofetil, azathioprine) to which belimumab has been added, either as first or second-line treatment, but the absence of data in patients not having responded to standard immunosuppressive therapies;
• the absence of specific data concerning pure histologic class V lupus nephritis, which represented a small proportion of patients in the clinical study, and for whom treatment is only recommended in the event of severe forms at risk of developing complications;

The Committee considers that BENLYSTA (belimumab) by the IV and SC route has a role in the care pathway, in combination with standard therapy including a corticosteroid plus an immunosuppressive therapy (cyclophosphamide, mycophenolate mofetil, azathioprine), either as first or second-line treatment, only in adult patients with histologic class III or IV, associated or otherwise with class V, active lupus nephritis.

It considers that BENLYSTA (belimumab) has no role in the care pathway in patients with pure histologic class V lupus nephritis, in the absence of specific robust data in this subpopulation, which differs in terms of its histology and treatment.

Special recommendations

Given the risk of hypersensitivity reactions with belimumab administered by the SC or IV route and of infusion reactions, which may be severe or life-threatening, it is recommended that the first injection of BENLYSTA (belimumab) SC be given under medical supervision and that BENLYSTA (belimumab) IV be administered by a qualified healthcare professional trained to give infusion therapy in an environment where resources for managing such reactions are immediately available.