title: A randomized trial of tacrolimus versus tacrolimus and prednisone for the maintenance of disease remission in noninfectious uveitis.
abstract: OBJECTIVE
  To compare tacrolimus monotherapy with tacrolimus and prednisone therapy for the maintenance of disease remission in subjects with noninfectious posterior segment intraocular inflammation (PSII).
  
  
  METHODS
  Randomized, controlled, phase 2b, open-label, dual-center noninferiority trial.
  
  
  METHODS
  Fifty-eight patients with sight-threatening PSII.
  
  
  METHODS
  Patients requiring a second-line systemic immunosuppressive agent to control their PSII were treated with therapeutic doses of oral tacrolimus. Those subjects who subsequently were able to taper their prednisone dose to 10 mg daily without disease reactivation were assigned randomly either to stop prednisone or to continue 7.5 to 10 mg prednisone daily for 9 months.
  
  
  METHODS
  Change in logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) and rate of patient withdrawal resulting from treatment inefficacy or intolerance.
  
  
  RESULTS
  Thirty-five patients successfully tapered their prednisone to 10 mg daily. Of these, 16 were allocated randomly to receive tacrolimus monotherapy and 19 to continue taking prednisone and tacrolimus dual therapy. The difference in the mean change in VA for monotherapy compared with the dual therapy group was less than 1 logMAR letter (logMAR, -0.008; 95% confidence interval, -0.108 to 0.092; P = 0.870). The proportion of patients who tolerated treatment and maintained disease remission for 9 months after randomization also was similar in both groups (monotherapy, 62.5%; dual therapy, 68.4%; P = 0.694). All monotherapy treatment failures were the result of disease reactivation, whereas 50% of dual-therapy failures were the result of drug intolerance.
  
  
  CONCLUSIONS
  This study provides preliminary evidence that corticosteroids can be withdrawn in tacrolimus-treated patients who are able to achieve control of PSII with 10 mg prednisone daily, and any advantage of dual therapy in the prevention of disease reactivation was offset by its greater treatment intolerance. These findings support the further evaluation of corticosteroid-free treatment in future phase 3 trials (International Standard Randomised Controlled Trial Number Register identification, ISRCTN46576063).
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Department of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Richard W J
authors.initials: RW
authors.lastname: Lee
authors.forename: Rosemary
authors.initials: R
authors.lastname: Greenwood
authors.forename: Hazel
authors.initials: H
authors.lastname: Taylor
authors.forename: Radgonde
authors.initials: R
authors.lastname: Amer
authors.forename: Sabine
authors.initials: S
authors.lastname: Biester
authors.forename: Jarka
authors.initials: J
authors.lastname: Heissigerova
authors.forename: John V
authors.initials: JV
authors.lastname: Forrester
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Dick
mesh_terms: D000284:Administration, Oral; D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060046:Maintenance Chemotherapy; D008297:Male; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014605:Uveitis / Q000188:drug therapy* / Q000503:physiopathology; D014792:Visual Acuity / Q000502:physiology
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D011241:Prednisone; D016559:Tacrolimus