POS0327 EFFICACY OF TWO YEARS OF TREATMENT WITH ANTI-IL-5/R THERAPIES ACCORDING TO HISTORIC DISEASE SEVERITY IN PATIENTS WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disorder characterised by asthma, hypereosinophilia, and vasculitis of small-to-medium vessels. Specific disease manifestations of EGPA may be more severe than others. The 1-year double-blind period of the MANDARA trial (NCT04157348) demonstrated that benralizumab 1x30mg was non-inferior to mepolizumab 3x100mg (administered subcutaneously every 4 weeks) for achieving remission in patients with relapsing or refractory EGPA. A post-hoc analysis of the double-blind period of the study demonstrated similar efficacy of anti-IL-5/R therapies regardless of history of severe disease. Objectives: To determine the efficacy of anti-IL-5/R therapies in patients with EGPA, according to presence or absence of historical evidence for severe disease, during the 1-year double-blind period and first year of the ongoing open-label extension (OLE) of the MANDARA study. Methods: Patients who completed the double-blind period were invited to enter the OLE during which they continued benralizumab (benra/benra, n=66) or switched from mepolizumab to benralizumab (mepo/benra, n=62). Endpoints at Week 104 included remission (Birmingham Vasculitis Activity Score [BVAS]=0 and oral glucocorticoid [OGC] dose ≤4 mg/day), OGC use, and safety. Data from both groups were pooled to evaluate these endpoints according to the presence/absence of a history of severe EGPA prior to study baseline. The ‘severe EGPA group' included patients with historic presence ever of at least one of the following: cardiomyopathy, glomerulonephritis, alveolar haemorrhage; or treatment with cyclophosphamide or rituximab. As per the exclusion criteria, no patients had severe manifestations of EGPA at trial entry. Results: Of 128 patients who entered the OLE, 42 (32.8%) had a history of severe EGPA (24 benra/benra, 18 mepo/benra) and 86 (67.2%) had no history of severe EGPA (42 benra/benra, 44 mepo/benra). A higher proportion of patients with a history of severe disease received non-OGC immunosuppressive therapy since diagnosis (severe EGPA: 32 [76.2%], non-severe EGPA: 45 [52.3%]) and had 3–5 relapses (severe EGPA: 14 [33.3%], non-severe EGPA: 12 [14.0%]) in the two years before study entry. A similar proportion of patients in both groups were ANCA-positive (severe EGPA: 12 [28.6%], non-severe EGPA: 23 [26.7%]). Similar adjusted rates of remission were achieved at Week 104 regardless of history of disease severity (severe EGPA: 74.4%, non-severe EGPA: 60.2%; difference: 14.28 [95% confidence interval (CI): –2.53, 31.10], p=0.0960; Figure 1). The adjusted rates for achieving remission by Week 24 and remaining in remission until Week 104 were also similar between groups (severe EGPA: 28.9%, non-severe EGPA: 20.9%; difference: 7.98 [95% CI: –7.52, 23.47], p=0.3129). During Weeks 101–104, a similar proportion of patients in the severe and non-severe EGPA groups had a ≥50% reduction from baseline in OGC dose (severe EGPA: 71.9%, non-severe EGPA: 67.2%; difference: 4.63 [95% CI: –12.11, 21.37], p=0.5875) and 54.8% versus 38.4%, respectively, had full withdrawal of OGCs (difference: 16.37 [95% CI: –1.54, 34.27), p=0.0732). Adverse events and serious adverse events were similar between groups regardless of disease severity (Table 1). Conclusion: Anti-IL-5/R therapies demonstrated similar efficacy regarding remission, OGC use, and safety profiles in patients with EGPA regardless of history of severe disease. These data suggest a role for anti-IL-5/R therapies in the treatment pathway, even in patients with a history of severe EGPA manifestations, consistent with EULAR treatment guidelines [1]. The role of anti-IL-5/R therapies for treatment of active severe manifestations of EGPA requires further studies and pooled data from real-world studies are needed to further validate this preliminary post-hoc analysis. REFERENCES: [1] Hellmich B, et al. Ann Rheum Dis. 2024;83:30–47. Figure 1 Table 1 . Acknowledgements: Medical writing support was provided by Caroline Ridley and Ella Palmer of inScience Communications, Springer Healthcare Ltd, UK, which was funded by AstraZeneca in accordance with Good Publication Practice 2022 guidelines. Disclosure of Interests: Bernhard Hellmich speaker fees and/or consultancies from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, GSK, InflaRx, Janssen, MSD, Novartis, Pfizer, Phadia, Roche and CSL Vifor, Peter A Merkel consulting and stock options in Kyverna, Q32, and Sparrow, consulting fees and research support from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GSK, InflaRx, and Takeda; consulting fees only from argenx, Cabaletta, CSL Behring, Dynacure, HiBio, Janssen, Novartis, NS Pharma, Regeneron Pharmaceuticals, and Visterra, research support only from Eicos, Electra, Forbius, Genentech/Roche, Neutrolis, and Sanofi/Genzyme, David R. W. Jayne speaker fees and/or consultancies from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, ChemoCentryx, Chugai, GSK, Novartis, Roche, Takeda, and Vifor Pharma; advisory board member for Aurinia, Chinook, GSK, and Takeda. Benjamin Terrier consulting fees from AstraZeneca, GSK, Novartis and Vifor Pharma, Florence Roufosse consulting fees from AstraZeneca, GSK, and Merck, Parameswaran Nair honoraria from Arrowhead, AstraZeneca, CSL Behring, GSK, and Sanofi, institution received grant support from AstraZeneca, Cyclomedica, Equillium, Foresee, Genentech, Sanofi and Teva, Nader Khalidi consulting fees only from GSK, Mallinckrodt Pharmaceuticals, Otsuka Pharmaceuticals, and Roche, consulting fees and research support from AbbVie, Bristol Myers Squibb and Sanofi, David J. Jackson consultancy fees and speakers' fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, and Sanofi Regeneron, research grants from AstraZeneca, Shunsuke Furuta speaker fees from Asahi Kasei Pharma, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Kissei Pharmaceutical, and Otsuka Pharmaceutical, consulting fees from Asahi Kasei Pharma, Lena Börjesson Sjö AstraZeneca and may own stock/stock options, Aadarsh Lal AstraZeneca and may own stock/stock options, Sofia Necander AstraZeneca and may own stock/stock options, Anat Shavit AstraZeneca and may own stock/stock options, Claire Walton AstraZeneca and may own stock/stock options, Michael Wechsler consulting, advisory, or speaking honoraria from the following: Allakos, Amgen, Areteia Therapeutics, Arrowhead Pharmaceutical, AstraZeneca, Avalo Therapeutics, Celldex, Connect Biopharma, Eli Lilly, Equillium, GSK, Incyte, Kinaset, Kymera, Merck, Phylaxis, Pulmatrix, Rapt Therapeutics, Recludix Pharma, Regeneron Pharmaceuticals, Roche/Genentech, Sanofi/Genzyme, Sentien, Sound Biologics, Tetherex Pharmaceuticals, Uniquity Bio, Upstream Bio, Verona Pharma, and Zurabio. © 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.

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