Rituximab Found to Be Safe, Effective for 2 AAV Types in Children
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Rituximab is safe and effective for inducing remission in two types of ANCA-associated vasculitis in children and adolescents: granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), according to data from a Phase 2a trial.
After one and a half years on the trial, all patients achieved remission, and safety data was consistent with data from adults with the disease.
Findings from this trial supported the U.S. and European approvals of rituximab, in combination with glucocorticoids, for the treatment of GPA and MPA patients, 2 years and older.
Updated results have now been published in a study, “Phase IIa global study evaluating rituximab for the treatment of pediatric patients with granulomatosis with polyangiitis or microscopic polyangiitis,” in Arthritis & Rheumatology.
Rituximab (originally sold as Rituxan in the U.S. and MabThera in Europe, with biosimilars now available) is an antibody that works by depleting B-cells, a type of immune cell that produces antibodies and is overactive in AAV.
After first being approved for use in adults with GPA or MPA as both an induction therapy (to push the condition into remission) and a maintenance therapy (to maintain remission), rituximab was tested for use in the pediatric population.
The PePRS Phase 2a study (NCT01750697) was an open-label, single-arm clinical trial evaluating the safety, tolerability, pharmacokinetics (the movement of a drug into, through, and out of the body), and preliminary efficacy of rituximab in patients, ages 2 to 17.
Sponsored by Roche, the developer of Rituxan and MabThera, the trial included 25 patients, median age 14 (range 6–17), across six countries in North America and Europe. Nineteen patients (76%) had GPA and six (24%) had MPA. Eighteen (72%) had newly diagnosed disease and seven (28%) had relapsing disease.
During the remission induction phase, patients received rituximab as an infusion (drip) into the vein once a week for four weeks, at a dose of 375 mg per square meters of body surface area.
They also received oral glucocorticoids, which were continuously tapered over six months, and preventive treatment against Pneumocystis jirovecii, a pneumonia-causing fungus. During follow-up, patients could receive additional rituximab infusions, if needed.
All patients completed the six-month remission induction phase of the study, and 56% of them achieved remission during that period. Remission was defined as having a score of zero on the Pediatric Vasculitis Activity Score (PVAS) and a maximum 0.2 mg/kg/day dose of glucocorticoids, or a PVAS of zero on two consecutive visits more than one month apart, regardless of glucocorticoid dose.
The percentage of patients meeting the criteria for remission increased to 92% after 12 months and 100% after 18 months. Remissions lasted as long as 3.5 years.
During the induction treatment, all patients experienced at least one adverse side effect, but most were mild to moderate and related to the infusion procedure itself. Other side effects included headaches and nausea. Seven patients had a total of 10 serious side effects and 17 had an infection. No deaths occurred during the study.
Among patients with available data, 19% developed antibodies against rituximab, which can limit the efficacy of treatment, but the researchers reported no increases in serious infusion-related reactions or differences in side effects among patients with or without such antibodies.
“In pediatric patients, rituximab was well tolerated and effective with an overall safety profile comparable with that of rituximab-treated adult patients with GPA or MPA,” the researchers wrote.
Clearance of rituximab from the body correlated with a patient’s body surface area, and calculation of the dose based on that area resulted in similar relative levels of the medicine in the pediatric patients as in the adult patients.
“Rituximab was associated with a positive benefit-risk profile for use in pediatric patients with active GPA or MPA,” the researchers concluded.
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