title: Clinical efficacy and immunological impact of tacrolimus in Chinese patients with generalized myasthenia gravis.
abstract: In this multicenter, open-label pilot study, the efficacy, safety, and immunological impact of tacrolimus in Chinese patients with generalized myasthenia gravis are assessed. Forty-seven generalized myasthenia gravis (MG) patients were enrolled into this study and given 3mg/day tacrolimus for 24 weeks. The primary efficacy measurements used to monitor response to tacrolimus in MG patients were the Osserman grade, the quantitative MG score (QMGS) recommended by the MGFA, the MG-specific manual muscle testing (MMT) score, and the MG-related activities of daily living (MG-ADL) scale. Also, reduction in steroid doses was used to monitor the effect of tacrolimus. Clinical evaluations were conducted at weeks 4, 8, 12, 16, 20, and 24, while immunological parameters were measured at weeks 4, 12, and 24. Measurements of the Osserman grade, QMGS, MMT, and MG-ADL all suggested improvement in patient health by the fourth week of treatment. Steroid dosage was reduced during the course of the study in 74.2% of the forty-three patients who completed the study. There were thirty-one reported adverse events in the study. Only one was considered serious. We found that tacrolimus reduced levels of the IFN-γ, IL-2, IL-10, and IL-13 cytokines and induced the proliferation of tolerogenic plasmacytoid dendritic cells after treatment. Tacrolimus did not change the population of T cell subtypes but did steadily reduce the population of BAFF-R(+) CD19(+) B cells over the course of the study. Our results show that tacrolimus improves the clinical condition of MG patients and is well tolerated. The decrease in IL-13 and reduction of BAFF-R(+) CD19(+) B cells may be related to the therapeutic effect of tacrolimus.
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: C-B
authors.initials: CB
authors.lastname: Zhao
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: X-Q
authors.initials: XQ
authors.lastname: Hu
authors.forename: J-H
authors.initials: JH
authors.lastname: Lu
authors.forename: C-Z
authors.initials: CZ
authors.lastname: Lu
authors.forename: B-G
authors.initials: BG
authors.lastname: Xiao
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000188:drug therapy* / Q000276:immunology*; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016559:Tacrolimus