POS0284 EFFECTIVENESS AND SAFETY OF MEPOLIZUMAB IN REMISSION MAINTENANCE AND REMISSION INDUCTION PHASES IN 48 PATIENTS WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS
Authors: M. Ueno, I. Miyagawa, S. Kubo, Y. Miyazaki, K. Hanami, K. Sonomoto, S. Nakayamada, Y. Tanaka
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The efficacy of mepolizumab (MPZ), an anti-IL-5 antibody for eosinophilic granulomatosis with polyangiitis (EGPA), has been reported. MPZ was approved for relapsing or refractory EGPA in 2018. We have reported the real-world effectiveness and safety of MPZ for relapsing and refractory EGPA in the maintenance phase (n=16) and in the remission induction phase (n=7). However, an evaluation with an extended observation period with a larger sample size is expected. <h3>Objectives:</h3> We evaluated the effectiveness and safety of MPZ (1) in the maintenance phase for relapsing and refractory EGPA (study 1) and (2) in the remission induction phase for severe EGPA (study 2) in 48 patients with EGPA in real clinical practice. <h3>Methods:</h3> This study consists of study 1(remission maintenance phase) and 2 (remission induction phase). Study 1: The 2-year effectiveness and safety in the maintenance phase of relapsing and refractory EGPA (N=33) were evaluated. Clinical data of 2 years before (Pre-MPZ group: month -24 to 0) and after (Post-MPZ group: month 0 to 24) MPZ introduction were compared. The primary endpoint was the remission-achieving rate in the Post-MPZ group (remission: BVAS 0 and GC[PSL] ≤ 4 mg/day). Secondary endpoints were GC-free remission rate, MPZ retention rate, BVAS, eosinophil counts (/μL), concomitant GC dose (mg/day), VDI, and safety. Study 2: The 1-year effectiveness and safety of MPZ (MPZ group, N=15) and the IVCY (IVCY group, N=18) were compared in patients with severe EGPA with organ involvements. The MPZ group was treated with high-dose GC and MPZ, and the IVCY group was treated with high-dose GC and IVCY. The primary endpoint was remission-achieving rate, and secondary endpoints were GC-free remission rate, changes in BVAS, eosinophil counts, concomitant GC dose, VDI, MPZ and IVCY (10-15 mg/kg biweekly, six times) retention rate, and safety. <h3>Results:</h3> Study 1: The primary endpoint was 72.7% (24/33), and GC-free remission was achieved in 48.5% (16/33). There were no significant changes in BVAS, eosinophil counts, and concomitant GC dose in the Pre-MPZ group (BVAS 0→0, eosinophil count 374→168, GC 6.0→5.0). BVAS, eosinophil counts, and concomitant GC dose significantly decreased in the MPZ group (BVAS 0→0 (p&lt;0.001), eosinophil count 168→32.3 (p=0.002), GC 5.0→0 (p&lt;0.001)). VDI increased significantly in the Pre-MPZ group (3.0→4.0 (P=0.010)), but not in the Post-MPZ group (4.0→4.0 (P=0.083)). The MPZ retention rate was 90.9% (30/33), and adverse events were significantly lower in the Post-MPZ group (p=0.022). Study 2: The two groups had no significant difference in patient background. The primary endpoint was 66.7% (10/15) in the MPZ group and 22.2% (4/18) in the IVCY group, which was significantly higher in the MPZ group (p=0.010). GC-free remission rate was 13.3% (2/15) in the MPZ group and 0% (0/18) in the IVCY group (p=0.110). BVAS decreased significantly in both groups (MPZ group: 16.0 to 0, IVCY group: 17.0 to 0), and there was no significant difference between groups. Eosinophil counts also decreased significantly in both groups (MPZ group: 6992→17.5, IVCY group: 5210→78), with no significant difference between the groups. The concomitant GC dose decreased significantly in both groups (MPZ group: 50→2.5, IVCY group: 58→6.0). The concomitant GC dose (MPZ group vs. IVCY group: 2.5 vs. 6.0 (p&lt;0.001)) and GC reduction rate (%) (MPZ vs. IVCY: -94.0 vs. -86.7 (p&lt;0.001)) were significantly higher in the MPZ group. VDI at 12 months was 1.0 in the MPZ group and 2.0 in the IVCY group, significantly lower in the MPZ group. MPZ retention rate was 100%, and the IVCY completion rate was 72.2%. Adverse events occurred in 26.7% (4/15) in the MPZ group and 61.1% (11/18) in the IVCY group, significantly lower in the MPZ group (p= 0.048). In all 48 patients, the remission-achieving and GC-free remission rates were 70.8% (34/48) and 37.5% (18/48), respectively. <h3>Conclusion:</h3> The effectiveness and safety of MPZ in the maintenance and remission induction phases were demonstrated. Based on the higher GC-sparing effect, MPZ can be a proper therapeutic option to achieve GC-free remission and avoid irreversible organ damage in real clinical practice. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Masanobu Ueno Masanobu Ueno has received a speaking fee from GlaxoSmithKline., Ippei Miyagawa: None declared, Satoshi Kubo Satoshi Kubo has received speaking fees from Eli Lilly, GlaxoSmithKline, Bristol-Myers, Abbvie, Eisai, Pfizer, Astra-Zeneca and also research grants from Daiichi-Sankyo, Abbvie, Boehringer Ingelheim, and Astellas., Yusuke Miyazaki Yusuke Miyazaki has received speaking fees from Eli Lilly and GlaxoSmithKline., Yusuke Miyazaki has received a grant from GlaxoSmithKline., Kentaro Hanami: None declared, Koshiro Sonomoto: None declared, Shingo Nakayamada S. Nakayamada has received speaking fees from Bristol-Myers, AstraZeneca, Pfizer, GlaxoSmithKline, Astellas, Asahi-kasei, Sanofi, Abbvie, Eisai, Chugai, Gilead, and Boehringer Ingelheim., S Nakayamada has received research grants from Mitsubishi-Tanabe., Yoshiya Tanaka Yoshiya Tanaka has received speaking fees from Eli Lilly, AstraZeneca, Abbvie, Gilead, Chugai, Behringer-Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer, Taiho., Yoshiya Tanaka has received grants from Mitsubishi-Tanabe, Eisai, Chugai, Taisho.