title: Randomized controlled trial of rituximab in patients with Graves' orbitopathy.
abstract: BACKGROUND
  Graves' orbitopathy (GO) is a potentially sight-threatening disease for which available medical therapy is not uniformly successful. Multiple case series suggest that rituximab (RTX) may be effective therapy for GO patients.
  
  
  OBJECTIVE
  To determine the efficacy of RTX in GO.
  
  
  METHODS
  It is a prospective, randomized, double-masked, placebo-controlled trial.
  
  
  METHODS
  The study was conducted at a large academic private practice.
  
  
  METHODS
  Twenty five patients with active moderate to severe GO were enrolled, and 21 completed the study to the primary endpoint.
  
  
  METHODS
  Two RTX infusions (1000 mg each) or two saline infusions were given 2 weeks apart.
  
  
  METHODS
  The primary endpoint was a reduction in clinical activity score (CAS) assessed as a continuum and separately as improvement by ≥ 2 points at 24 weeks. Secondary endpoints included success and failure rates, proportions showing clinically significant improvement in proptosis, lid fissure width, diplopia score, lagophthalmos and disease severity, and changes in those parameters, orbital fat/ muscle volume and quality-of-life.
  
  
  RESULTS
  The treatment groups were similar in all parameters at baseline. The last observation was carried forward if the patient discontinued prematurely. No differences were found in the proportions of patients showing CAS improvement at 24 weeks (25% placebo; 31% RTX, P = .75) or in CAS decrease from baseline to 24 or 52 weeks [mean 1.5 points (1.8 SD) placebo; 1.2 (2 SD) RTX at 24 weeks, P = .73]. Similarly, there were no differences between groups in any of the secondary endpoints at either 24 or 52 weeks. There were four adverse events (AE) in 3/12 placebo patients and 11 AE in 8/13 RTX-treated patients; 5/6 moderate or severe AE occurred in the RTX group.
  
  
  CONCLUSIONS
  RTX offered no additional benefit over placebo to our patients with active and moderate to severe GO and carried with it non-negligible adverse effects.
authors.affiliation: Division of Endocrinology and Metabolism (M.N.S., B.G.C.L., R.S.B.), Department of Ophthalmology (J.A.G., E.A.B.), and Department of Health Sciences Research (T.P.), Mayo Clinic, 200 First St SW, Rochester, Minnesota 55905.
authors.forename: Marius N
authors.initials: MN
authors.lastname: Stan
authors.forename: James A
authors.initials: JA
authors.lastname: Garrity
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Carranza Leon
authors.forename: Thapa
authors.initials: T
authors.lastname: Prabin
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bradley
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Bahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D049970:Graves Ophthalmopathy / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab