medwireNews: Rituximab is well tolerated and shows good efficacy in children with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), global phase 2a study results show.
Paul Brogan (UCL Great Ormond Street Institute of Child Health, London, UK) and co-authors, writing in Arthritis & Rheumatology, explain that “[r]ituximab is increasingly being used as a first-line treatment for induction of remission 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 in particular are still limited.
To address this, Brogan and his team designed the PePRS study, which included 25 patients (median age 14 years) with newly-onset or relapsed GPA (76%) or MPA (24%) intravenously once weekly rituximab 375 mg/ m2 received. for 4 consecutive weeks plus a glucocorticoid taper as part of a 6 month remission induction period.
They were then followed for a minimum of 12 additional months (up to 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.”
Particularly during the remission induction phase, all patients experienced at least one adverse reaction (AE), mostly infusion-related reactions, occurring 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 severe AEs in seven patients and 31 infection-related AEs in 17 patients, mostly upper respiratory tract infections. There were no deaths or AE-related discontinuations during the study.
Exploratory efficacy analyzes showed that remission, as assessed by the Pediatric Vasculitis Activity Score, occurred in 56% of patients at 6 months, 92% at 12 months and in all patients at 18 months.
The researchers also analyzed pharmacokinetic data and found that the rituximab dosing regimen, adjusted for body surface area, resulted in comparable drug exposure levels in pediatric patients with GPA or MPA as in adult patients.
Note that Brogan and colleagues say the PePRS study has led to the approval of rituximab in the US and Europe for the treatment of GPA and MPA in pediatric patients 2 years of age and older.
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Arthritis Rheumatol 2021; doi:10.1002/art.41901