title: Efficacy and safety of low-dose tacrolimus for active rheumatoid arthritis with an inadequate response to methotrexate.
abstract: OBJECTIVE
  To determine the efficacy and safety of low-dose tacrolimus in Korean rheumatoid arthritis (RA) subjects with an inadequate response to methotrexate (MTX).
  
  
  METHODS
  This was a multicenter, open-label study conducted at five Korean sites. Fifty-six patients with active RA, despite treatment for ≥ 1 month with a stable, maximally tolerated dosage of oral MTX (median dosage, 15 mg/wk), were enrolled and received 1.5 mg/day of tacrolimus as a single oral dose once per day for 16 weeks while continuing to receive MTX. All other disease-modifying anti-rheumatic drugs were discontinued, whereas stable dosages of nonsteroidal anti-inflammatory drugs and oral corticosteroids (≤ 10 mg/day of prednisone or an equivalent corticosteroid) were allowed. The primary clinical response criterion was the American College of Rheumatology's definition of 20% improvement (ACR20) at the end of treatment.
  
  
  RESULTS
  The ACR20 response rate was 42.9% (24 of 56 patients) in patients who had received tacrolimus at least once. The overall ACR50 and ACR70 responses at the end of treatment for all patients were 30.4% and 10.7%, respectively. Throughout the treatment period, 37 patients experienced 71 adverse events (AEs) in total, and four patients left the study because of AEs. In addition, 15 patients in total experienced treatment-related AEs. Throughout the treatment period, two patients were reported to experience two serious AEs, and one patient left the study because of a serious AE.
  
  
  CONCLUSIONS
  In patients whose active RA persists despite treatment with MTX, low-dose tacrolimus in combination with MTX appears to be safe and well tolerated, and provides clinical benefit.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Won-Seok
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Sang-Il
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Wonkwang University Hospital, Iksan, Korea.
authors.forename: Myeung-Soo
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.
authors.forename: Sung-Il
authors.initials: SI
authors.lastname: Kim
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Shin-Seok
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Wan-Hee
authors.initials: WH
authors.lastname: Yoo
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D012074:Remission Induction; D056910:Republic of Korea; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016559:Tacrolimus; D008727:Methotrexate
keywords: Arthritis, rheumatoid; Methotrexate; Tacrolimus