Off-label use of biological therapies in relapsing and/or refractory eosinophilic granulomatosis with polyangiitis (churg-strauss)

Background/Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss) is characterized by pulmonary and systemic small-vessel necrotizing vasculitis, vascular and/or extravascular granulomas, eosinophilia and tissue infiltration by eosinophils, occurring in individuals with asthma. Glucocorticoids (GCs) effectively control the disease, but relapses and/or GCdependence are frequent, leading to immunosuppressant and/or biological therapy use. We examined off-label biological therapy use for relapsing and/or refractory EGPA. Methods: This retrospective nationwide study included patients with EGPA meeting ACR criteria and/or Chapel Hill Consensus Conference definitions. Treatment efficacy and safety were recorded. Remission was defined as the absence of asthma and/or sinonasal exacerbations and vasculitis manifestations with a prednisone dose ≤7.5 mg/day, and partial response as requiring >7.5 mg of prednisone daily. Results: Thirty-three patients (22 men, 11 women; median age 50 years) were included. Thirteen (39%) received rituximab (RTX) and 20 (61%) omalizumab (OMA). Previous treatments were: methylprednisolone infusions (54%), oral GCs (100%), IV cyclophosphamide (60%), azathioprine (75%), methotrexate (24%), mycophenolate mofetil (6%), plasmapheresis (6%) and/or co-trimoxazole (33%). RTX was mainly prescribed for pulmonary involvement (92%), sinusitis (69%), peripheral neuropathy (61.5%) and cardiac involvement (46%). OMA was prescribed for pulmonary involvement (90%) and sinusitis (90%). At inclusion, median (range) BVAS for the RTX and OMA groups, respectively, were 4 (0-19) and 2 (0-9). After median follow-up of 20 months, remissions, partial responses and therapeutic failures, respectively, were 38%, 23% and 38% for RTX recipients, and 40%, 20% and 80% for the OMA group. Median BVAS dropped to 0 for both groups. A GC-sparing effect was obtained for both groups but was greater for RTX recipients: median GC dose decreased from the baseline 16 mg/day to 15 at 3 months, 10 at 6 and 12 months and 7.5 at the last follow-up vs. 12.5 mg/day to 11.25 at 3 months, 12 at 6 months, 10 at 12 months and 9 at the last follow-up for the OMA group. Two patients stopped RTX because of severe asthma flares and another because of refractory disease. Eleven patients stopped OMA: 2 because of vasculitis relapses, 2 for severe asthma flares, 4 had refractory disease and 3 achieved remissions. The latter 3 patients then took azathioprine; no relapses occurred after discontinuing OMA. The only minor side effect, nausea, occurred in the RTX group. Conclusion: The results of this study suggest that RTX and OMA may achieve GC-sparing in relapsing and/or refractory EGPA, but the latter remains frequent.