Background/Purpose:

Children with ANCA vasculitides frequently present with life-threatening organ manifestations including alveolar hemorrhage, critical subglottic stenosis and renal failure due to rapidly progressive glomerulonephritis (GN). The current initial management for adults includes high-dose steroids and cyclophosphamide. The majority of patients experience a serious disease flare. In adult studies, Rituximab is highly effective in the treatment of severe vasculitis flares. The aim of this study was to evaluate efficacy and safety of Rituximab for treatment of severe disease flare in children with ANCA vasculitides.

Methods: A single-center cohort study of consecutive children with ANCA vasculitis treated with Rituximab for severe disease flares was performed between January 2009 until July 2011. Children were managed according to a previously implemented protocol. Clinical, laboratory and imaging features, previous therapies, including efficacy and safety were documented in serial assessments. Disease activity was captured by Pediatric Vasculitis Activity Score (PVAS). Safety evaluation included adverse events and disease-related damage domains by Vasculitis Damage index (VDI).

Results:

Six children (5 females, 1 male) were included, median age at diagnosis 7.8 years. Diagnosis: All children had lung involvement including 4 presenting with hemorrhage, 3 with renal disease and 3 with ENT involvement, including subglottic stenosis in 2. ANCAs: +c-ANCA +PR3 in 4 patients, + p-ANCA +MPO in 1 and -ANCA + MPO in 1. All children previously received high dose steroids and cyclophosphamide; previous maintenance treatment included: azathioprine in 1, MMF in 2 and MTX in 4 children. Two patients were still on MTX maintenance at time of flare. Disease flare: median disease duration until time to flare was 16 months (12-62 months); 5/6 had lung flares (hemorrhage, new nodules) and 1 child developed new GN. Treatment: All 6 children received Rituximab (500 mg/m2, 2 doses q2weeks) plus high dose prednisone (2 mg/kg/day, max 60 mg/day) and one patients continued on MTX maintenance. Plasmapheresis just prior to Rituximab was used in 2 children. Efficacy: The median PVAS at time of flare was 6; 4 children had no evidence of active disease at 3 months (PVAS=0), and 5 at 12 months. All patients completely depleted their B-cells. After Rituximab therapy, ANCAs were positive in 4 patients at 3 months and 2 patients after 12 months. Safety: Infusion reactions were uncommon. One child experienced itchiness, fever and myalgias during the 2nd cycle of infusions. One patient developed Pneumocystis Jiroveci pneumonia. Five children received a second course of Rituximab at 6-13 months postinitial course upon return of their B-cells.

Conclusion:

A complete response (PVAS=0) was seen in 67% of children with severe disease flares of ANCA vasculitis following treatment with Rituximab and high dose prednisone. This is a significantly higher response rate than with the current induction treatment for childhood ANCA vasculitides. Retreatment with Rituximab was required in the majority of children. Rituximab therapy was effective and safe; however long-term observations will determine the safety of repeated Rituximab treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rituximab-for-severe-disease-flares-in-childhood-anca-vasculitides/