title: A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behçet's disease.
abstract: OBJECTIVE
  To investigate the safety and efficacy of daclizumab (Zenapax, humanized anti-Tac, HAT) in controlling the ocular manifestations of Behçet's disease.
  
  
  METHODS
  Randomized, placebo-controlled, double-masked clinical trial.
  
  
  METHODS
  Seventeen participants with Behçet's disease experiencing at least two prior ocular attacks and requiring treatment with immunosuppressive agents for the ocular complications of Behçet's disease.
  
  
  METHODS
  Participants received either intravenous placebo or daclizumab (1 mg/kg) infusions every two weeks for six weeks, then every four weeks while continuing their standard immunosuppressive regimens. If clinically indicated, tapering of the standard immunosuppressive medications was allowed after six months of study enrollment. Complete ocular and physical examinations and an adverse event assessment were performed at baseline and prior to each study infusion.
  
  
  METHODS
  Primary safety endpoints were the development of a life-threatening complication or a severe opportunistic infection. Primary efficacy outcomes were the number of ocular attacks and an assessment of systemic immunosuppressive medications required during the study, including the ability to taper concomitant immunosuppressive therapy.
  
  
  RESULTS
  Nine participants randomized to daclizumab and eight to placebo were followed monthly. Follow-up ranged from one to 34 months, with a median follow-up of 15 months. Two participants randomized to daclizumab discontinued study therapy prior to the end of the study for personal reasons. No participant experienced a safety endpoint, and visual acuity remained stable in all participants during the course of the study. Ten participants (six daclizumab, four placebo) experienced ocular attacks requiring therapy. The median ocular attack rate during the study was greater in the daclizumab arm than the placebo arm (median 1.27 vs. 0.17 attacks/year, respectively). Participants in the placebo arm also experienced a greater reduction in the immunosuppressive medication score compared to participants receiving daclizumab (median -4.0 vs. -1.0, respectively).
  
  
  CONCLUSIONS
  The observed results in the placebo group demonstrate that careful follow-up and treatment with standard combination immunosuppressive therapy can be effective for the management of the ocular complications of Behçet's disease. In our small study, there was no suggestion that daclizumab was beneficial in comparison with placebo. However, the low observed attack rate limited our ability to make a definitive treatment group comparison.
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1857, USA.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Buggage
authors.forename: Grace
authors.initials: G
authors.lastname: Levy-Clarke
authors.forename: Hatice N
authors.initials: HN
authors.lastname: Sen
authors.forename: Roxana
authors.initials: R
authors.lastname: Ursea
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Srivastava
authors.forename: Eric B
authors.initials: EB
authors.lastname: Suhler
authors.forename: Chandra
authors.initials: C
authors.lastname: Altemare
authors.forename: Gisela
authors.initials: G
authors.lastname: Velez
authors.forename: Jack
authors.initials: J
authors.lastname: Ragheb
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Robert B
authors.initials: RB
authors.lastname: Nussenblatt
authors.forename: Alison T
authors.initials: AT
authors.lastname: Bamji
authors.forename: Puspha
authors.initials: P
authors.lastname: Sran
authors.forename: Thomas
authors.initials: T
authors.lastname: Waldmann
authors.forename: Darby J S
authors.initials: DJ
authors.lastname: Thompson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001528:Behcet Syndrome / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D000077561:Daclizumab; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D014605:Uveitis / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab