title: The efficacy and safety of additional administration of tacrolimus in patients with rheumatoid arthritis who showed an inadequate response to tocilizumab.
abstract: OBJECTIVE
  Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown.
  
  
  METHODS
  Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8 mg/kg/month] and 2 subcutaneous [324 mg/month] TCZ treatments, methotrexate 6.1 mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI] ≥ 5.8, 18 secondary non-responders) were additionally treated with TAC (1.1 mg/day), and enrolled in this 24-week, prospective study.
  
  
  RESULTS
  Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28-CRP) from 3.3 at baseline to 2.1 at week 24 (p < 0.001), CDAI from 17.7 to 7.6 (p < 0.001), and serum matrix metalloproteinase-3 levels from 232.8 to 66.2 ng/ml (p < 0.001). About 15 patients (75%) achieved low disease activity or remission (DAS28-CRP ≤2.7 or CDAI ≤10) at week 24.
  
  
  CONCLUSIONS
  Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option.
authors.affiliation: a Department of Orthopaedic Surgery , Japan Community Healthcare Organization, Osaka Hospital , Osaka , Japan.|b Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , Osaka , Japan.|c Department of Orthopaedic Surgery , Osaka Rosai Hospital , Osaka , Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kaneshiro
authors.affiliation: b Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , Osaka , Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Ebina
authors.affiliation: b Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , Osaka , Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirao
authors.affiliation: c Department of Orthopaedic Surgery , Osaka Rosai Hospital , Osaka , Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tsuboi
authors.affiliation: a Department of Orthopaedic Surgery , Japan Community Healthcare Organization, Osaka Hospital , Osaka , Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: d Department of Orthopaedic Surgery , National Hospital Organization Osaka Minami Medical Center , Osaka , Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Nampei
authors.affiliation: c Department of Orthopaedic Surgery , Osaka Rosai Hospital , Osaka , Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Nagayama
authors.affiliation: e Department of Orthopaedic Surgery , Toneyama National Hospital , Osaka , Japan , and.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Takahi
authors.affiliation: b Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , Osaka , Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Noguchi
authors.affiliation: a Department of Orthopaedic Surgery , Japan Community Healthcare Organization, Osaka Hospital , Osaka , Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Owaki
authors.affiliation: f Department of Rheumatology , National Hospital Organization Osaka Minami Medical Center , Osaka , Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hashimoto
authors.affiliation: b Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , Osaka , Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy; D002097:C-Reactive Protein / Q000032:analysis; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D008875:Middle Aged; D062072:Patient Acuity; D011446:Prospective Studies; D012074:Remission Induction / Q000379:methods; D012720:Severity of Illness Index; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D019278:Matrix Metalloproteinase 3; C502936:tocilizumab; D016559:Tacrolimus
keywords: Biologics; Inadequate response; Rheumatoid arthritis; Tacrolimus; Tocilizumab