medwireNews: Rituximab is well tolerated and shows good efficacy in children with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), global phase 2a study findings indicate.
Writing in Arthritis & Rheumatology, Paul Brogan (UCL Great Ormond Street Institute of Child Health, London, UK) and co-authors explain that “[r]ituximab is increasingly being used as a first-line remission induction treatment in children with [anti-neutrophil cytoplasmic antibody-associated vasculitides] instead of cyclophosphamide.”
But they add that formal data evaluating the safety, pharmacodynamics, and pharmacokinetics of rituximab in pediatric patients with GPA or MPA, specifically, are still limited.
To address this, Brogan and team set up the PePRS study, in which 25 patients (median age 14 years) with new-onset or relapsing GPA (76%) or MPA (24%) received intravenous rituximab 375 mg/m2 once a week for 4 consecutive weeks plus a tapering course of glucocorticoids as part of a 6-month remission induction period.
They were then followed up for a minimum of 12 additional months (maximum 4.5 years), during which time they could receive further treatment, including rituximab, at the discretion of the study investigators. On average, each patient received eight rituximab infusions, with the amount ranging from four to 28.
Brogan et al report that the “safety profile of rituximab in pediatric patients was consistent with that previously observed in adult patients with GPA or MPA and the well-characterized safety profile of rituximab in approved autoimmune indications.”
Specifically, during the remission induction phase all patients experienced at least one adverse event (AE), most commonly infusion-related reactions, which occurred in 60% and generally after the first infusion.
The authors say that the AEs were typically grade 1 or 2 in severity, but during the induction phase there were 10 serious AEs among seven patients, and 31 infection-related AEs in 17 patients, most commonly upper respiratory tract infections. There were no deaths or AE-related discontinuations throughout the study.
Exploratory efficacy analyses revealed that remission, assessed using the Pediatric Vasculitis Activity Score, occurred in 56% of patients at 6 months, 92% at 12 months, and in all patients by 18 months.
The researchers also analyzed pharmacokinetic data and found that the body surface area-adjusted rituximab dosing regimen led to similar drug exposure levels in pediatric patients with GPA or MPA to those seen in adult patients.
Of note, Brogan and colleagues say that the PePRS study has led to rituximab approval in the USA and Europe for the treatment of GPA and MPA in pediatric patients aged 2 years and older.
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