Long‐Term Safety and Efficacy of Eculizumab in Aquaporin‐4 IgG‐Positive NMOSD

Objective During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin‐4 immunoglobulin G‐positive neuromyelitis optica spectrum disorder (AQP4‐IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open‐label extension (OLE; NCT...

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Published in:	Annals of neurology Vol. 89; no. 6; pp. 1088 - 1098
Main Authors:	Berthele, Achim, Shang, Shulian, Sabatella, Guido, Manin, Analisa, Muñoz, Daniel Julio, Amor, Jorge, Obregon, Carolina Daniela Diaz, Chiesa, Ana, Hardy, Todd, Trewin, Benjamin, Sedal, Leslie, Crnosija, Luka, Gabelic, Tereza, Pitha, Jiri, Krasulova, Eva, Petersen, Thor, Lehmann‐Horn, Klaus, Zettl, Uwe, Meister, Stefanie, Lau, Alexander Yuk Lun, Au, Lisa Wing Chi, Ma, Sze Ho, Mok, Chung Tong Vincent, Messina, Silvia, Proietto, Maria, Shalom, Haggiag, Boriello, Giovanna, De Angelis, Floriana, Yokota, Takanori, Nishida, Yoichiro, Sanjo, Nobuo, Sato, Nozomu, Shibuya, Kazumoto, Murai, Hiroyuki, Yamaguchi, Hiroo, Takahashi, Yuji, Saida, Takahiko, Nakamura, Shinichi, Nasu, Tetsuya, Saida, Kyoko, Ukon, Shinichiro, Kaneko, Kimihiko, Takai, Yoshiki, Koga, Michiaki, Sano, Yasuteru, Kim, Su‐Hyun, Kim, Byung‐Jo, Kim, YooHwan, Koo, Yong Seo, Cho, Eun Bin, Choi, MiSong, Kim, JunSoon, Kim, Seung Woo, Jung, JinWoo, Khabirov, Farit, Averyanova, Lyudmila, Yarmoschuk, Asya, Balyazina, Elena, Timofeeva, Alla, Samulyzhko, Iuliana, Sepulveda, Juan Jose Ochoa, Viña, Nazaret Pelaez, Garcia, Nuria Gonzalez, Delgado, Fernando Romero, Yin, Jiu‐Haw, Siritanan, Krittika, Thearapati, Chidchanoke, Konpan, Phanpaphon, Potigumjon, Artit, Kurt, Can Ebru Bekircan, Ayhan, Gokce, Tutuncu, Melih, Altintas, Ayse, Sengun, Ihsan, Kaya, Derya, Efendi, Husnu, Onar, Musa Kazim, Sahin, Yanki, Arndt, Heike, Jenkins, Damian, Tackley, George, Frishberg, Benjamin, Khoury, Chaouki, Hammond, Nancy, Wang, Yunxia, Cooper, Gregory, Tornes, Leticia, Jacobs, Daniel, Iyengar, Revathi, Klafter, Mark, Sadek, Ahmed, Bar‐Or, Amit, Suski, Valerie, Orie, Ryan, Flanagan, Eoin, Clardy, Stacey, Rose, John, Soldon, Mateo, Naismith, Robert, Stuart, Susan
Format:	Journal Article
Language:	English
Published:	Hoboken, USA John Wiley & Sons, Inc 01-06-2021 Wiley Subscription Services, Inc
Subjects:	Adult Adverse events Aged Antibodies, Monoclonal, Humanized - therapeutic use Aquaporin 4 Aquaporin 4 - immunology Aquaporins Autoantibodies - immunology Autoantigens - immunology Complement Inactivating Agents - therapeutic use Confidence intervals Female Humans IgG antibody Immunoglobulin G Immunoglobulin G - immunology Immunosuppressive agents Infections Longitudinal Studies Male Middle Aged Monoclonal antibodies Neuromyelitis Neuromyelitis Optica - drug therapy Neuromyelitis Optica - immunology Patients Placebos Recurrence Safety
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Summary:	Objective During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin‐4 immunoglobulin G‐positive neuromyelitis optica spectrum disorder (AQP4‐IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open‐label extension (OLE; NCT02003144) evaluating eculizumab's long‐term safety and efficacy. Methods Patients who completed PREVENT could enroll in the OLE to receive eculizumab (maintenance dose = 1,200 mg/2 weeks, after a blinded induction phase). Safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis. Results Across PREVENT and the OLE, 137 patients received eculizumab and were monitored for a median (range) of 133.3 weeks (5.1–276.9 weeks), for a combined total of 362.3 patient‐years (PY). Treatment‐related adverse event (AE) and serious adverse event (SAE) rates were 183.5 in 100 PY and 8.6 in 100 PY, respectively. Serious infection rates were 10.2 in 100 PY in eculizumab‐treated patients versus 15.1 in 100 PY in the PREVENT placebo group. No patient developed a meningococcal infection. At 192 weeks (3.7 years), 94.4% (95% confidence interval [CI], 88.6–97.3) of patients remained adjudicated relapse‐free. The adjudicated annualized relapse rate was 0.025 (95% CI = 0.013–0.048) in all eculizumab‐treated patients versus 0.350 (95% CI = 0.199–0.616) in the PREVENT placebo group. During the OLE, 37% of patients (44 of 119 patients) stopped or decreased background immunosuppressive therapy use. Interpretation This analysis demonstrates that eculizumab's long‐term safety profile in NMOSD is consistent with its established profile across other indications. This analysis also demonstrated the sustained ability of long‐term eculizumab treatment to reduce relapse risk in patients with AQP4‐IgG+ NMOSD. ANN NEUROL 2021;89:1088–1098
Bibliography:	Members of the PREVENT Study Group are listed in Table S1. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	0364-5134 1531-8249
DOI:	10.1002/ana.26049