Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial

• Published in: Multiple sclerosis and related disorders Vol. 47; p. 102641
• Main Authors: Terzi, Murat, Yountz, Marcus, Amor, Jorge David, Laffue, Alfredo, Cordoba, Marta, Ingolotti, Mariana, Chiesa, Ana Elisa, Bolner, Gisel Edith, Heshmat, Saman, Dalic, Linda, Barton, Joshua, Garber, Justin, Taha, Marinda, Krasulova, Eva, Tyblova, Michaela, Bendele, Sandrine, Diem, Ricarda, Kowarik, Markus Christian, Pongratz, Viola Maria, Schweiker, Andreas, Zettl, Uwe Klaus, Klinke, Jan, Au, Lisa Wing-Chi, Ma, Karen Ka-Yan, Chisari, Clara Grazia, Bergamaschi, Roberto, Mallucci, Giulia, Quartuccio, Esmeralda Maria, Pozzilli, Carlo, Masuda, Hiroki, Uchida, Tomohiko, Matsuse, Dai, Shinoda, Koji, Kodani, Yoshimi, Yamashita, Tomomi, Kaneko, Kimihiko, Nishiyama, Shuhei, Oyama, Azusa, Sakuma, Motonari, Sawada, Yuko, Nishida, Yoichiro, Ozaki, Kokoro, Matsubara, Yumi, Hyun, Jae Won, Koo, Yong Seo, Choi, Kyomin, Min, Ju-Hong, Kim, Yool-hee, Bozhenkina, Tatyana, Khoroshilova, Inessa, Chernikova, Irina, Duran, Sabas Boyero, Roman, Carmen Bahamonde, Sepulveda, Juan Jose Ochoa, Viña, Nazaret Pelaez, Guillamon, Elena Miñano, Perez, Francisco Jesus Lopez, Tonda, Patricia Torres, Li, Shan-Ni, Kulkantrakorn, Kongkiat, Lolekha, Praween, Arayawichanont, Arkhom, Kurt, Ebru Bekircan, Gulo, Aysenur, Altintas, Ayse, Cam, Abdulsamet, Siva, Aksel, Gulo, Pinar, Balkan, Bengu, Becerikli, Gulsah, Onar, Musa Kazim, Ozberk, Mehlika Berra, Boz, Cavit, Callison, Karen, Inocelda, Andrew, Nicholas, Jacqueline A, Boster, Aaron, Esquibel, Lawanda, Fagatele, Lilly, Banas, Thomas M, Bultemeyer, Marlene C, Kocks, Debi, Jassam, Yasir N, Winkley, James, Godwin, Diana, Maldonado, Janice, Hernandez, Jeffrey, Zetka, Eric S, Lindquist, Justin, Sadek, Ahmed H, Verma, Navin, Williamson, Eric, Dobbins, Jessica, Pinckney, Ashley, McKeon, Andrew, Sagen, Jessica, Carter, Jonathan L, Snyder, Charlene R Hoffman, Thomas, Martha, Repovic, Pavle
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-01-2021
• Subjects: Adult; Antibodies, Monoclonal, Humanized - therapeutic use; Aquaporin 4; Aquaporin-4 immunoglobulin G-positive; Eculizumab; Humans; Neuromyelitis Optica - drug therapy; Neuromyelitis optica spectrum disorder; Relapse; Rituximab - therapeutic use; Safety; Subgroups; ARR; Relapse; Neuromyelitis optica spectrum disorder; AE; Aquaporin-4 immunoglobulin G-positive; PY; AQP4; HR; IST; Subgroups; NMOSD; SD; SAE; NE; Eculizumab; MG; Safety; EDSS
• ISSN: 2211-0348; 2211-0356
• DOI: 10.1016/j.msard.2020.102641

•Eculizumab reduces relapse risk regardless of disease duration and relapse history.•Eculizumab is effective regardless of concomitant therapies or prior rituximab use.•Eculizumab is well tolerated in patients receiving immunosuppressive therapy.•There were few serious infections with eculizumab regardless of prior rituximab use.
Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT.
In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity.
The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder.
Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate.
NCT01892345 (ClinicalTrials.gov).
[Display omitted]