title: Adequate tacrolimus concentration for myasthenia gravis treatment.
abstract: A single, oral dose of 3 mg/day tacrolimus, approved for myasthenia gravis (MG) treatment in Japan, was shown to reduce steroid dose and anti-acetylcholine receptor (AChR) antibody titers as well as to improve MG symptoms. However, no studies have investigated the association between tacrolimus concentration and its clinical efficacy in MG. In this study, we aimed to determine the optimal tacrolimus concentration for MG treatment.
  
  
  
  The trough tacrolimus concentration in 51 patients with MG (positive for anti-AChR antibody, n = 48; negative for anti-AChR and anti-muscle-specific tyrosine kinase antibodies, n = 3) who received 3 mg/day tacrolimus for more than 1 year was measured using a chemiluminescent enzyme immunoassay. The clinical characteristics of patients with MG as well as the dose of prednisolone used before and after tacrolimus treatment were evaluated retrospectively.
  
  
  
  The median trough tacrolimus concentration was 5.4 (range, 2.9-7.6) ng/mL, which was correlated with 'minimal manifestation or better status' (P = 0.0190, r = 0.3273) and the reduction in anti-AChR antibody 1 year after tacrolimus initiation (P = 0.0170, r = 0.3465). When the cut-off value for tacrolimus was defined as 4.8 ng/mL using a receiver operating characteristic curve, patients with adequate tacrolimus concentration (≥4.8 ng/mL) showed more reduction in anti-AChR antibody titers and more improvement in MG-related activities in daily life scores. More patients with adequate tacrolimus concentration achieved 'minimal manifestation or better status' compared with those with low tacrolimus concentration.
  
  
  
  An adequate tacrolimus concentration is required for better MG prognosis.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba.
authors.forename: T
authors.initials: T
authors.lastname: Kanai
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba.
authors.forename: A
authors.initials: A
authors.lastname: Uzawa
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba.|Department of Neurology, Neurology Chiba Clinic, Chiba.
authors.forename: N
authors.initials: N
authors.lastname: Kawaguchi
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba.|Department of Neurology, JR Tokyo General Hospital, Shibuya-ku, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Himuro
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba.
authors.forename: F
authors.initials: F
authors.lastname: Oda
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba.
authors.forename: Y
authors.initials: Y
authors.lastname: Ozawa
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba.
authors.forename: S
authors.initials: S
authors.lastname: Kuwabara
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007564:Japan; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000188:drug therapy*; D011239:Prednisolone / Q000627:therapeutic use*; D011379:Prognosis; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D007166:Immunosuppressive Agents; D011239:Prednisolone; D016559:Tacrolimus
keywords: minimal manifestation; myasthenia gravis; tacrolimus concentration