title: Treatment Outcomes With Rituximab in 100 Patients With Neuromyelitis Optica: Influence of FCGR3A Polymorphisms on the Therapeutic Response to Rituximab.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Jeong
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Hyun
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: AeRan
authors.initials: A
authors.lastname: Joung
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Jo
authors.affiliation: Department of Laboratory Medicine and Hematologic Malignancy Branch, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Hwang
authors.affiliation: Biometric Research Branch, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: Sooin
authors.initials: S
authors.lastname: Yun
authors.affiliation: Biometric Research Branch, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: Jungnam
authors.initials: J
authors.lastname: Joo
authors.affiliation: Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Korea.
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D051401:Aquaporin 4 / Q000276:immunology; D004185:Disability Evaluation; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D012189:Retrospective Studies; D000069283:Rituximab / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: C496030:AQP4 protein, human; D000906:Antibodies; D051401:Aquaporin 4; C496124:FCGR3A protein, human; D007155:Immunologic Factors; D017452:Receptors, IgG; D000069283:Rituximab