POS1175 ANTI-IL5 THERAPY IN EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS: DOSAGE, EFFICACY AND OUTCOME IN A LARGE COHORT OF PATIENTS IN REAL LIFE (REVAS STUDY)

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 play 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/ENT manifestations difficult to treat. Objectives: To describe the indications, dosage, efficacy and safety, of eosinophil targeted therapies in patients with EGPA in a real practice. Methods: Retrospective study evaluating all patients with EGPA included at REVAS Registry, treated with anti-IL5 therapy, in order to assess the effectiveness and safety of this therapy. Treatment response was evaluated from 3 months to the censoring data. Complete response (CR) was defined as the absence of asthma and/or sinonasal exacerbations with a prednisone dosage of ≤5 mg/day, and partial response (PR) when the prednisone dosage was ≥5 mg/day. Statistical analysis was performed using SSPS 21 package. Results: Fifty patients (median age 47 years) were evaluated. Forty-five (90%) patients received mepolizumab (38 patients 100 mg every 4 weeks and 7 patients 300 mg every 4 weeks) for a mean period of 31 (1-68) months ; 4 (8%) received benralizumab (30 mg every 4 weeks) for a mean of 33 (7-42) months, and 3 (6%) received resilizumab (n=3, 6%) for a mean period of 54,3 (43-67) month. Anti-Il5 therapy was indicated for severe steroid-dependent asthma (94%) and/or persistent sinonasal involvement (80%) 11 (22%) patients also had symptoms of active vasculitis (5 mononeuritis multiplex, 3 miocarditis, 2 infiltrative cutaneous lesions, 1 orbital pseudotumor). ANCA were positive in 27 (54%) cases with MPO specificity. All patients were receiving corticosteroids at the time of anti-IL5 therapy beginning, with a mean dosage of 11,5 mg/day. A total of 11 (22%) patients had previously received omalizumab, that was changed to mepolizumab in 9 cases, reslizumab in 1 and benralizumab in another, due to PR (n=5) or recurrence of asthma and/ or sinusitis (n=6) after a long period of treatment (70.5 months). Anti-IL5 therapy was given concomitantly to AZA in 7 cases, MTX in 3, and RTX in 2. 38 (84,4%) patients treated with mepolizumab achieved a CR after 6-18 months of treatment. The median dosage of prednisone 6 months after mepolizumab, benralizumab and reslizumab initiation was 6 (5-15) mg/day, 5.3 (2.5-10) mg/day, and 3.3 (0-5) mg/day, respectively. The median dosage of prednisone 12 months after mepolizumab, benralizumab and reslizumab beginning was 3.5 (0-5) mg/day, 3.1 (0-5) mg/day and 2.5 (0-5) mg/day, respectively. The median number of exacerbations decreased from 2.5 over the 6 months previous to therapy beginning to 1 in the following 12 months. CS were stopped in 12 (24%) patients. All 3 drugs were safe and well tolerated. During the follow-up period, three patients experienced a major relapse of the disease, and were successfully treated with RTX in conjunction with mepolizumab, with no serious adverse events. Mepolizumab dosage was reduced to 100 mg every 6 weeks in 50% of cases. In one case mepolizumab was changed by benralizumab due to PR. Conclusion: Mepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. Both doses should be compared in the setting of a controlled trial. Benralizumab and reslizumab are also effective. Sequential therapy with anti-IL5 drugs and rituximab was safe and effective in achieving remission in patients with a major relapse of the disease.