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Background: Rituximab in combination with glucocorticoids (GC) is approved to treat adult patients (pts) with GPA or MPA; however, limited data exist on the safety and efficacy of rituximab in paediatric pts with these potentially life- and organ-threatening diseases.
Objectives: To report the interim safety, pharmacokinetics (PK) and exploratory efficacy data from the 6 month remission induction phase of a Phase IIa international, open-label, 18 month clinical study of rituximab in paediatric pts with GPA or MPA.
Methods: Pts aged ≥2 to≤18 years with newly diagnosed or relapsing GPA/MPA received 4 intravenous (IV) rituximab infusions of 375 mg/m2 body surface area (BSA) on Days 1, 8, 15 and 22 with concomitant GC 1 mg/kg/day (max 60 mg/day) tapered to 0.2 mg/kg/day minimum (max 10 mg/day) by Month 6. All pts received 3 doses of pulse IV methylprednisolone (30 mg/kg/day, max 1 g/day) prior to first rituximab infusion and mandatory prophylaxis for Pneumocystis jiroveci infection. Pts were also pre-medicated with acetaminophen and an antihistamine, 1 hour before each rituximab infusion. Adverse events (AEs) and laboratory data were measured at each study visit (1, 2, 4 and 6 months). Plasma samples for PK analysis were collected throughout the study; clearance and area under the curve (AUC) were calculated using population PK modelling from the RAVE study of rituximab in adult pts with GPA/MPA.1 For exploratory efficacy assessment, the Paediatric Vasculitis Activity Score (PVAS) was measured at each study visit.
Results: Of the 25 pts enrolled, 19 (76%) had GPA and 6 (25%) had MPA (median [range] age 146–17 years; 80% female). Median (range) disease duration was 0.5 (0.2–0.72) months; 2 pts had received prior cyclophosphamide therapy. All received 4/4 rituximab infusions and completed the 6 month induction phase. By Month 6, all pts had experienced ≥1 AE. The most common AEs by system organ class were infections and infestations in 16 pts (64%). AE terms reported in ≥3 pts are listed in the table 1. Eleven serious AEs occurred in 7 pts (28%), including 3 serious infections (viral gastroenteritis, one lower and one upper respiratory tract infection). 32% of pts had ≥1 infusion related reaction (IRR). No serious IRRs or deaths were reported. The relationship between AUC and BSA was flat and comparable to adult pts. A total of 13 pts (52%) achieved remission by 6 months, defined as PVAS of 0 and GC dose 0.2 mg/kg/day (max 10 mg/day) or PVAS of 0 on 2 consecutive readings≥4 weeks apart irrespective of GC dose.
Abstract OP0332 – Table 1 Adverse events reported in ≥3 patients
Conclusions: In the initial 6 months of this first global clinical trial of rituximab in paediatric pts with GPA/MPA, rituximab was generally safe and well tolerated. The overall safety profile and PK parameters were comparable to adults with GPA/MPA. No new safety signals were observed. However, the study size and interim nature of the analysis limit firm conclusions. The clinical trial and additional efficacy, PK and safety analyses are ongoing.
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Acknowledgements: This study is funded by F. Hoffmann-La Roche.
Disclosure of Interest: P. Brogan Grant/research support from: Roche, SOBI, Novartis, Chemocentryx, Consultant for: Roche, SOBI, UCB, Speakers bureau: SOBI, Novartis, G. Cleary Speakers bureau: AbbVie, O. Kasapcopur: None declared, S. Rangaraj: None declared, R. Yeung Consultant for: Novartis, Eli Lilly, P. Brunetta Shareholder of: Roche, Employee of: Genentech, Inc., J. Cooper Employee of: Genentech, Inc., P. Pordeli Employee of: Roche, P. Lehane Employee of: Roche
DOI: 10.1136/annrheumdis-2018-eular.2150