CHICAGO – Rituximab demonstrated a high degree of effectiveness with no safety surprises in the first-ever major clinical trial of the potent B-cell inhibitor conducted in pediatric patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis, Jennifer Cooper, MD, PharmD, said at the annual meeting of the American College of Rheumatology.
“This is exciting news. We know that rituximab is very effective in treating adults with GPA and MPA, both in terms of inducing remission and even for maintenance therapy for this rare and severe disease. A lot of pediatric rheumatologists would like to have access to rituximab. Some are even using it for this condition. But until now there were no data in children. I hope this study improves access to rituximab for pediatric patients with ANCA-associated vasculitis,” said, a pediatric rheumatologist at the University of Colorado, Denver.
She presented theof the PePRS (Pediatric Polyangiitis and Rituximab Study), a phase 2a, single-arm, open-label, long-term of 25 patients in six countries. She anticipates the results will be practice changing, given that pediatric GPA and MPA are recognized as severe systemic autoimmune disorders with a high unmet need for new therapies.
“I don’t believe there are plans for a randomized, controlled trial. Since we now have the pharmacokinetic and safety data in children, we’ll hopefully be able to use extrapolation and our exploratory efficacy endpoints to gain a pediatric indication, or at least a label update for these patients based on this study,” Dr. Cooper continued.
A total of 19 patients had GPA and 6 had MPA, with a median disease duration of 6 months at study entry. All received three pulsed doses of methylprednisolone during the screening period. Then for induction remission they got four once-weekly intravenous infusions of rituximab (Rituxan) at 375 mg/m2 as well as oral corticosteroids, which were tapered from 1 mg/kg per day to 0.2 mg/kg per day over the course of the first 6 months. After that, two-thirds of patients received additional rituximab at their provider’s discretion.
The remission rate by 6 months as defined by Pediatric Vasculitis Activity Score (PVAS) criteria was 56%. At 12 months, the rate was 92%, and at 18 months the rate of remission and sustained disease control was 100%. The mean and median durations of remission were 72 and 56 weeks, respectively.
These results in pediatric patients are comparable to those seen in adults in the landmark RAVE (Rituximab in ANCA-Associated Vasculitis) trial (), where 64% of patients reached remission at 6 months, Dr. Cooper noted.
All 25 patients were able to tolerate the four rituximab infusions for remission induction. The main side effect was infusion-related reactions. Overall, 32% of patients experienced such reactions in response to their first infusion, 20% with the second, 12% with the third, and only 8% with the fourth.
Eight patients withdrew from the study after 18 months, mostly because of transfer to adult care. The remaining participants were followed for as long as 4.5 years.
F. Hoffmann-La Roche and Genentech sponsored the PePRS study. Dr. Cooper was a Genentech clinical research fellow at the time.
SOURCE: Brogan P at al.