320. PEDIATRIC OPEN-LABEL CLINICAL STUDY OF RITUXIMAB FOR THE TREATMENT OF GRANULOMATOSIS WITH POLYANGIITIS AND MICROSCOPIC POLYANGIITIS

Background: PePRS is a Phase IIa international, multicenter, open-label single arm study of rituximab in pediatric patients (pts) with newly diagnosed or relapsing granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Methods: Pts aged ⩾2 to ⩽ 18 years with recurrence or new onset of potentially organ- or life-threatening disease were included. Pts with severe disease requiring mechanical ventilation due to alveolar hemorrhage, plasmapheresis or hemodialysis at screening were excluded. Pulsed intravenous (IV) methylprednisolone (3 doses) were administered during the screening period followed by 4 weekly IV rituximab infusions of 375 mg/m2 and concomitant oral glucocorticoid taper. After the 6-mo remission induction phase, pts received standard of care treatment (including additional rituximab infusions if required) for disease control. Visits occurred at 1, 2, 4 and 6 mos and every 3 mos thereafter for at least 18 mos. The pediatric vasculitis activity score (PVAS) was used for exploratory efficacy assessments. Remission was defined as a PVAS of 0 and oral prednisone or prednisolone equivalent dose of ⩽ 0.2 mg/kg/day (max 10 mg/day). Results: Of the 25 pts enrolled from 11 centers, 19 (76%) had GPA and 6 (24%) had MPA. Most were female (20 pts [80%]), white (17 pts [68%]), with a median (range) age was 14 (6-17) years. Most pts (18/25) had new-onset disease. Median baseline PVAS was 8 (IQR 5-15). Median (range) duration of follow-up was 24 (16-54) mos. All 25 pts completed the first 4 rituximab infusions and the 6-mo remission induction phase; 24 of 25 completed ⩾18 mos of follow-up. All pts had ⩾ 1 adverse event (AE) during the first 6 mos; infusion-related reactions (IRRs) were the most common (Table). IRRs occurred in 32% of pts with the first infusion and were less frequent thereafter. Overall, infections occurred in 68% of pts (upper respiratory tract infection was the most frequent [16% of pts]). Ten serious AEs (SAEs) occurred in 7 pts during the 6-mo remission induction phase, including 1 IRR. Over the entire study, 27 SAEs occurred in 12 pts; no deaths were reported. Exploratory efficacy assessment showed 56% of pts achieved PVAS remission by mo 6, 92% by mo 12 and 100% by mo 18. Mean (range) duration of remission was 72 (7-193) wks. Conclusion: In this first global clinical trial of rituximab in pediatric pts with GPA/MPA, rituximab was well tolerated with an overall safety profile comparable to rituximab-treated adults with GPA/MPA. No new safety signals were observed. All patients achieved remission by 18 mos. Disclosures: P. Brogan – grant/research support: Roche, SOBI, Novartis, Chemocentryx; consultant: Roche, SOBI, UCB; speakers bureau: SOBI, Novartis. G. Cleary – speakers bureau: AbbVie. O. Kasapcoput & S. Rangaraj – none declared. R. Yeung – consultant: Novartis, Eli Lilly. P. Brunetta – employee of Genentech (at the time of the study). J. Cooper – Genentech clinical research fellow (at the time of the study). P. Kirchner, P. Pordeli & P. Lehane – employees of Roche. This study was funded by F. Hoffmann-LaRoche Ltd and Genentech, Inc. Third-party writing assistance was furnished by Health Interactions, Inc. Common Adverse Events Reported in ≥ 10% of Patients During Remission Induction Phase AE, adverse event.

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