Rituximab Treatment of Patients with Severe, Corticosteroid-Resistant Thyroid-Associated Ophthalmopathy
Received 24 February 2009; received in revised form 17 May 2009; accepted 21 May 2009. published online 08 October 2009.
Purpose
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).
Design
Retrospective, interventional case series.
Participants
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.
Main Outcome Measures
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.
Financial Disclosure(s)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Available online: October 8, 2009.
1Jules Stein Eye Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
2Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
3Division of Molecular Medicine, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
4Division of Endocrinology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
5Los Angeles Biomedical Institute at Harbor-UCLA Medical Center, Torrance, California
6Greater Los Angeles Veterans Administration, Los Angeles, California
7Department of Ophthalmology and Visual Science, the Chinese University of Hong Kong, Hong Kong, China
Correspondence: Raymond S. Douglas, MD, PhD, Jules Stein Eye Institute, David Geffen School of Medicine, University of California at Los Angeles, 100 Stein Plaza, Suite 2-267, Los Angeles, CA 90095
Manuscript no. 2009-272.
Dr. Khanna and Dr. Chong contributed equally to this study.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Supported in part by the National Institutes of Health, Bethesda, Maryland (grant nos.: EY008976, EY011708, DK063121, EY016339, RR00425, K23 AR053858); an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York; a Research to Prevent Blindness Career Development Award; and the Bell Charitable Foundation.
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