Rituximab treatment of patients with severe, corticosteroid-resistant thyroid-associated ophthalmopathy.
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.
Khanna
Dinesh
D
Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Chong
Kelvin K L
KK
Afifiyan
Nikoo F
NF
Hwang
Catherine J
CJ
Lee
Diana K
DK
Garneau
Helene Chokron
HC
Goldberg
Robert A
RA
Darwin
Christine H
CH
Smith
Terry J
TJ
Douglas
Raymond S
RS
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
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D005938:Glucocorticoids; D007155:Immunologic Factors; D000069283:Rituximab