Treatment Outcomes With Rituximab in 100 Patients With Neuromyelitis Optica: Influence of FCGR3A Polymorphisms on the Therapeutic Response to Rituximab

• Published in: Archives of neurology (Chicago) Vol. 72; no. 9; p. 989
• Main Authors: Kim, Su-Hyun, Jeong, In Hye, Hyun, Jae-Won, Joung, AeRan, Jo, Hyo-Jin, Hwang, Sang-Hyun, Yun, Sooin, Joo, Jungnam, Kim, Ho Jin
• Format: Journal Article
• Language: English
• Published: Chicago American Medical Association 01.09.2015
• Subjects: Cells; Clinical outcomes; Eye diseases; Monoclonal antibodies; Polymerase chain reaction; Polymorphism
• ISSN: 2168-6149; 2168-6157

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. 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. 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/m...) 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. 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. 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). 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. (ProQuest: ... denotes formulae/symbols omitted.)