Su-Hyun Kim1, In Hye Jeong1, Jae-Won Hyun1, AeRan Joung1, Hyo-Jin Jo1, Sang-Hyun Hwang2, Sooin Yun3, Jungnam Joo3, Ho Jin Kim1. 1. Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea. 2. Department of Laboratory Medicine and Hematologic Malignancy Branch, Research Institute and Hospital of National Cancer Center, Goyang, Korea. 3. Biometric Research Branch, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
Abstract
IMPORTANCE: Despite the increased use of rituximab therapy in neuromyelitis optica spectrum disorder (NMOSD), the overall efficacy and safety of long-term rituximab treatment in a large group of patients is uncertain. Furthermore, the identification of a predictor of rituximab response is an important issue for assessing the individual risk-benefit of therapy and making treatment decisions. OBJECTIVE: To assess the long-term clinical efficacy and safety of rituximab treatment in patients with NMOSD and the influence of fragment c gamma receptor 3A (FCGR3A) polymorphisms on rituximab response. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 100 patients with relapsing NMOSD treated with rituximab for at least 6 months, from February 1, 2006, to January 31, 2015, at the institutional referral center. After induction therapy, a single infusion of rituximab (375 mg/m2) as maintenance therapy was administered whenever a reemergence of CD27+ memory B cells among peripheral blood mononuclear cells occurred. Using an allele-specific polymerase chain reaction-based method, the gene polymorphisms FCGR3A-V158F were assessed. MAIN OUTCOMES AND MEASURES: The primary end point was annualized relapse rate; disability (Expanded Disability Status Scale score), safety of rituximab treatment, event of insufficient memory B-cell depletion following rituximab, and time to retreatment of rituximab were secondary end points. RESULTS: By January 31, 2015, a total of 100 patients received repeated rituximab treatment during a median of 67 months. Of these patients, 41 had more than 5 years' follow-up and 24 had more than 7 years' follow-up. The annualized relapse rate was reduced significantly by 96% (mean [SD] annualized relapse rate of prerituximab vs postrituximab, 2.4 [2.0] vs 0.1 [0.6]) and disability improved or stabilized in 96% of patients. Rates of adverse events were generally stable. The FCGR3A-F allele was associated with a risk of relapse while receiving rituximab treatment (additive model, P < .05; recessive model, P = .04; maximum, P = .03) and insufficient memory B-cell depletion (additive model, P = .03; recessive model, P = .03; maximum, P = .03). CONCLUSIONS AND RELEVANCE: Repeated rituximab treatment for NMOSD was observed in an increasing number of patients and increasing duration of exposure and maintained good efficacy and a safety profile consistent with previous reports. The finding of a relationship between FCGR3A genetic polymorphisms and rituximab response suggests the importance of individualized rituximab treatment strategies in NMOSD.
IMPORTANCE: Despite the increased use of rituximab therapy in neuromyelitis optica spectrum disorder (NMOSD), the overall efficacy and safety of long-term rituximab treatment in a large group of patients is uncertain. Furthermore, the identification of a predictor of rituximab response is an important issue for assessing the individual risk-benefit of therapy and making treatment decisions. OBJECTIVE: To assess the long-term clinical efficacy and safety of rituximab treatment in patients with NMOSD and the influence of fragment c gamma receptor 3A (FCGR3A) polymorphisms on rituximab response. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 100 patients with relapsing NMOSD treated with rituximab for at least 6 months, from February 1, 2006, to January 31, 2015, at the institutional referral center. After induction therapy, a single infusion of rituximab (375 mg/m2) as maintenance therapy was administered whenever a reemergence of CD27+ memory B cells among peripheral blood mononuclear cells occurred. Using an allele-specific polymerase chain reaction-based method, the gene polymorphisms FCGR3A-V158F were assessed. MAIN OUTCOMES AND MEASURES: The primary end point was annualized relapse rate; disability (Expanded Disability Status Scale score), safety of rituximab treatment, event of insufficient memory B-cell depletion following rituximab, and time to retreatment of rituximab were secondary end points. RESULTS: By January 31, 2015, a total of 100 patients received repeated rituximab treatment during a median of 67 months. Of these patients, 41 had more than 5 years' follow-up and 24 had more than 7 years' follow-up. The annualized relapse rate was reduced significantly by 96% (mean [SD] annualized relapse rate of prerituximab vs postrituximab, 2.4 [2.0] vs 0.1 [0.6]) and disability improved or stabilized in 96% of patients. Rates of adverse events were generally stable. The FCGR3A-F allele was associated with a risk of relapse while receiving rituximab treatment (additive model, P < .05; recessive model, P = .04; maximum, P = .03) and insufficient memory B-cell depletion (additive model, P = .03; recessive model, P = .03; maximum, P = .03). CONCLUSIONS AND RELEVANCE: Repeated rituximab treatment for NMOSD was observed in an increasing number of patients and increasing duration of exposure and maintained good efficacy and a safety profile consistent with previous reports. The finding of a relationship between FCGR3A genetic polymorphisms and rituximab response suggests the importance of individualized rituximab treatment strategies in NMOSD.
Authors: Marelize Swart; Wesley M Stansberry; Victoria M Pratt; Elizabeth B Medeiros; Patrick J Kiel; Fei Shen; Bryan P Schneider; Todd C Skaar Journal: J Mol Diagn Date: 2019-02-20 Impact factor: 5.568
Authors: Elizabeth Cotzomi; Panos Stathopoulos; Casey S Lee; Alanna M Ritchie; John N Soltys; Fabien R Delmotte; Tyler Oe; Joel Sng; Ruoyi Jiang; Anthony K Ma; Jason A Vander Heiden; Steven H Kleinstein; Michael Levy; Jeffrey L Bennett; Eric Meffre; Kevin C O'Connor Journal: Brain Date: 2019-06-01 Impact factor: 13.501
Authors: Maureen A Mealy; Su-Hyun Kim; Felix Schmidt; Reydmar López; Jorge A Jimenez Arango; Friedemann Paul; Dean M Wingerchuk; Benjamin M Greenberg; Ho Jin Kim; Michael Levy Journal: Mult Scler Date: 2017-08-31 Impact factor: 6.312
Authors: Michael Zhong; Anneke van der Walt; Maria Pia Campagna; Jim Stankovich; Helmut Butzkueven; Vilija Jokubaitis Journal: Neurotherapeutics Date: 2020-10-14 Impact factor: 7.620
Authors: Philippe Cabre; M Mejdoubi; S Jeannin; H Merle; Y Plumelle; G Cavillon; D Smadja; R Marignier Journal: J Neurol Date: 2018-02-17 Impact factor: 4.849