FRI0265 ANTI-IGE AND ANTI-IL5 THERAPY FOR EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS

Abstract

Background: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss syndrome, is a rare type of anti-neutrophil cytoplasm antibody-associated vasculitis, associated with asthma, nasal poliposis and rinosinusitis, in which eosinophils paly a key role. Eosinophil targeted therapies alone or associated to conventional treatment with corticosteroids and immunosuppressant drugs may be useful in patients with refractory disease or asthma difficult to treat. Objectives: To describe the efficacy and safety of eosinophil targeted therapies in patients with relapsing or refractory EGPA Methods: Retrospective study including all patients with EGPA included at the REVAS Registry, who were treated with omalizumab, mepolizumab or resilizumab. Complete response (CR) was defined as the absence of asthma and/or sinonasal exacerbations with a prednisone dosage of < 7.5 mg/day, and partial response (PR) when the prednisone dosage was > 7.5 mg/day. Statistical analysis was performed using SSPS 20 package. Results: Seventeen patients (median age 49 years) received omalizumab (n=9) for a mean period of 53.4 (5-91) months, mepolizumab (n=7) for a mean period of 13.6 (5-16) months, or resilizumab (n=1) for a mean period of 7 months, for severe steroid-dependent asthma (94.1%) and/or sinonasal involvement (82.4%). ANCA were positive in 8 (47.1%) cases with MPO specificity in 7 cases. All patients were receiving corticosteroids with a mean dosage of 15 mg/day prior to eosinophil targeted therapies institution. Four (57.1%) patients treated with omalizumab achieved a CR, 1 a PR, and 2 had no improvement. The median dosage of prednisone 6 months after omalizumab initiation was 10 (2.5-10) mg/day and the median dosage after 12 months 5 (0-10) mg/day. The median number of exacerbations decreased from 4 over the 6 months previous to therapy startment to 2 in the following 12 months. Both patients refractory to omalizumab were treated with mepolizumab with CR at 6 months in 1 case. Treatment with mepolizumab was also started in 4 patients treated with omalizumab after a prolonged period of treatment (72.4 months), due to recurrence of asthma and/or sinusitis, and peripheral blood eosinophilia >10%. Three (75%) patients achieved a CR, and 1 patient experienced a major vasculitis relapse needing immunosuppressant drugs. Six (85.7%) patients initially treated with mepolizumab achieved a complete remission after 6-12 months of treatment. One patient achieved a PR. The median dosage of prednisone 6 months after mepolizumab initiation was 5 (3.1-6.8) mg/day and the median dosage after 12 months 3.5 (0-5) mg/day. The median number of exacerbations decreased from 2.5 over the 6 months previous to therapy startment to 1 in the following 12 months. The patient treated with resilizumab achieved a CR at 6 months of therapy. All 3 drugs were safe and well tolerated. Conclusion: The results of the present study suggest that eosinophil targeted therapies have a corticosteroid-sparing effect in EGPA patients with asthmatic and/or sinonasal manifestations, and that may be used sequentially in refractory cases. However, reducing the corticosteroid dosage may also increase the risk of severe EGPA flares. More data are needed to widely recommend this therapy in EGPA patients.