title: Rituximab treatment of patients with severe, corticosteroid-resistant thyroid-associated ophthalmopathy.
abstract: OBJECTIVE
  To study the effectiveness of anti-CD20 (rituximab [RTX]; Rituxan; Genentech, Inc., South San Francisco, CA) therapy in patients with severe, corticosteroid (CS)-resistant thyroid-associated ophthalmopathy (TAO).
  
  
  METHODS
  Retrospective, interventional case series.
  
  
  METHODS
  Six consecutive subjects with severe, progressive TAO unresponsive to CS.
  
  
  METHODS
  Electronic medical record review of consecutive patients receiving RTX during the previous 18 months. Responses to therapy were graded using standard clinical assessment and flow cytometric analysis of peripheral lymphocytes.
  
  
  METHODS
  Clinical activity score (CAS), proptosis, strabismus, treatment side effects, and quantification of regulatory T cells.
  
  
  RESULTS
  Six patients were studied. Systemic CS failed to alter clinical activity in all patients (mean CAS+/-standard deviation, 5.3+/-1.0 before vs. 5.5+/-0.8 during therapy for 7.5+/-6.4 months; P = 1.0). However, after RTX treatment, CAS improved from 5.5+/-0.8 to 1.3+/-0.5 at 2 months after treatment (P<0.03) and remained quiescent in all patients (CAS, 0.7+/-0.8; P<0.0001) at a mean follow-up of 6.2+/-4.5 months. Vision improved bilaterally in all 4 patients with dysthyroid optic neuropathy (DON). None of the 6 patients experienced disease relapse after RTX infusion, and proptosis remained stable (Hertel measurement, 24+/-3.7 mm before therapy and 23.6+/-3.7 mm after therapy; P = 0.17). The abundance of T regulatory cells, assessed in 1 patient, increased within 1 week of RTX and remained elevated at 18 months of follow-up.
  
  
  CONCLUSIONS
  In progressive, CS-resistant TAO, rapid and sustained resolution of orbital inflammation and DON followed treatment with RTX.
  
  
  BACKGROUND
  The author(s) have no proprietary or commercial interest in any materials discussed in this article.
authors.affiliation: Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
authors.forename: Kelvin K L
authors.initials: KK
authors.lastname: Chong
authors.forename: Nikoo F
authors.initials: NF
authors.lastname: Afifiyan
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Hwang
authors.forename: Diana K
authors.initials: DK
authors.lastname: Lee
authors.forename: Helene Chokron
authors.initials: HC
authors.lastname: Garneau
authors.forename: Robert A
authors.initials: RA
authors.lastname: Goldberg
authors.forename: Christine H
authors.initials: CH
authors.lastname: Darwin
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Smith
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Douglas
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects; D004351:Drug Resistance; D005094:Exophthalmos / Q000175:diagnosis / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000627:therapeutic use*; D049970:Graves Ophthalmopathy / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009915:Orbit / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D000069283:Rituximab; D013285:Strabismus / Q000175:diagnosis / Q000503:physiopathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D005938:Glucocorticoids; D007155:Immunologic Factors; D000069283:Rituximab