Background: The anti-interleukin 5 mepolizumab is licensed at the dosage of 100mg/4 weeks subcutaneously for the treatment of severe eosinophilic asthma, and at the dosage of 300mg/4 weeks for eosinophilic granulomatosis with polyangiitis (EGPA), following the positive results of the MIRRA trial [1]. In the last years, a growing number of observational cohort studies reported on the successful use of mepolizumab for EGPA in the real-life clinical setting, also at the dosages approved for eosinophilic asthma (i.e., 100mg/4 weeks) [2-4]. However, real-life effectiveness and safety data are mostly limited to the first 12 months of treatment.

Objectives: To assess the long-term effectiveness, safety, and persistence of mepolizumab 100mg/4 weeks in patients with EGPA.

Methods: We included patients with EGPA treated with mepolizumab 100mg/4 weeks at any of the 116 referral centres for EGPA across 16 European countries, participating to the European EGPA Study Group. Only patients with at least 12 months of follow-up following mepolizumab beginning were included. Complete response to treatment was assessed up to 60 months after initiation of mepolizumab, and was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg/day, as reported in literature [1,4].

Results: 209 patients with at least 12 months of follow-up on mepolizumab 100mg/4 weeks were included. Of them, 6 had initially received mepolizumab 300mg/4 weeks, and had switched to mepolizumab 100mg/4 weeks within the first year due to achievement of remission or financial reasons [4]. At 12 months of follow-up, 35% of patients were on complete response. Between 12 and 24 months of follow-up, 24 patients increased mepolizumab dosage to 300mg/4 weeks due to inefficacy, and at 24 months of follow-up, 49/136 patients (36%) were on complete response. At 48 months of follow-up, 88 patients were still actively treated with mepolizumab 100mg/4 weeks, and of them, 40 (45%) were on complete response. Other 8 patients had increased mepolizumab to 300mg/4 weeks due to poor disease control, particularly of respiratory manifestations. Between 48 and 60 months of follow-up, additional 6 patients increased mepolizumab dosage to 300mg/4 weeks. Of the 48 patients with active follow-up on mepolizumab 100mg/4 weeks at 60 months, 22 (46%) were on complete response. Regarding safety, at 12 months 7 patients reported adverse events (AEs) that had occurred in the previous 6 months of therapy, including one asthma exacerbation requiring hospital admission. Five patients reported AEs between 12 and 24 months of treatment (all non-serious), 6 patients between 36 and 48 months (including one serious AE related to a hospitalization for thyroid cancer), and other 4 patients between 48 and 60 months of treatment (including one serious AE with hospitalization for prostatic cancer). All non-serious AEs were related to infections, respiratory exacerbations or asthenia.

Conclusion: Long-term treatment with mepolizumab 100 mg/4 weeks appears effective and safe for EGPA. Switch to a higher dosage (300mg/4 weeks) might be required in patients inadequately controlled with low dosage.

REFERENCES: [1] Wechsler et al, NEJM 2017.

[2] Canzian et al, Arthritis Rheum 2020.

[3] Caminati et al, JACIP 2020.

[4] Bettiol et al, Arthritis Rheum 2022.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.