MABTHERA - GPA (maladie de Wegener) et polyangéite microscopique (PAM) pédiatrique

Key points

Favourable opinion for reimbursement for the induction of remission, in combination with glucocorticoids, in paediatric patients (aged ≥ 2 to < 18 years old) with severe, active granulomatosis with polyangiitis (Wegener's, GPA) and microscopic polyangiitis (MPA).

What therapeutic improvement?

Therapeutic improvement in management.

Role in the care pathway?

The objectives of treatment in ANCA-associated vasculitis are to induce remission and prevent relapses, at the same time limiting treatment-associated adverse effects and the sequelae of the disease.

There are no specific guidelines in children in France. The use of remission induction treatments in children with severe or active GPA and MPA is extrapolated from the guidelines in adults.

The treatment of severe forms of GPA and MPA combines corticosteroids with immunosuppressive therapies prescribed long-term for a duration of more than 18 months. A first induction phase lasting around 3 to 6 months aims to obtain disease remission.

The remission induction treatment of severe and active GPA and MPA is based primarily on the combination of oral prednisone, possibly preceded by a bolus of methylprednisolone, and IV cyclophosphamide for at least 3 months (usually 6 infusions).

Cyclophosphamide is liable to promote the development of infections and cancers - predominantly bladder cancers - and, at high doses, to cause sterility, sometimes permanent, particularly when cyclophosphamide is prescribed orally since the cumulative doses are higher than following intravenous administration. For a similar efficacy, the oral form is less well tolerated than the IV form.

As first-line treatment, rituximab may be prescribed in the same way as cyclophosphamide. The choice of treatment is left to the clinician’s assessment when patients are treated for a first flare of the disease. The decision takes into account the patient’s history, pre-existing morbidity factors, the disease to be treated and the patient’s opinion.

According to the most recent revised 2019 French national diagnostic and care protocol (PNDS) guidelines, rituximab should be used preferentially as immunosuppressive therapy in combination with glucocorticoids in paediatric patients (children and adolescents) for the remission induction treatment of severe forms of GPA and MPA.

Role of the medicinal product in the care pathway

MABTHERA (rituximab) is a first-line treatment for the induction of remission, in combination with glucocorticoids, in paediatric patients (aged ≥ 2 to < 18 years old) with severe, active GPA (Wegener's) and MPA.

Special recommendations

In view of the complexity of treatment of these rare diseases and the absence of specific guidelines, the Committee recommends that children be treated following consultation of a paediatric “rare autoimmune diseases and systemic diseases” reference centre or specialist centre, possibly with the involvement of an adult reference or specialist centre, to discuss the therapeutic strategy to be adopted.