Introduction: This study was done in order to assess the safety and efficacy of rituximab treatment for thyroid eye disease (TED, another name for Graves’ ophthalmopathy [GO]).
Methods: There were 12 TED patients in this study, which was a prospective, open-label, interventional clinical trial. All 12 patients had Clinical Activity Scores (CAS) (VISA classification [Vision, Inflammation, Strabismus, and Appearance/Exposure]) of ≥ 4, and they were followed for 1 year after rituximab treatment. The rituximab was given intravenously at 1000 mg on days 1 and 15.
At baseline, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 52 weeks after the day 15 infusion, CAS, peripheral B-lymphocyte levels, thyroid autoantibody levels, and thyroid function tests were recorded. Over that 1-year period, thyroid-stimulating immunoglobulin and thyroid-stimulating hormone levels were also monitored.
A change from baseline CAS was the primary endpoint.
Results: At each follow-up visit over the year, CAS scores showed a statistically significant decrease from baseline. However, thyroid-stimulating immunoglobulin and thyroid-stimulating hormone levels did not show a significant change.
Within 1 month after rituximab treatment, B-cell depletion was seen; the peripheral B-lymphocyte count began to increase at 36 weeks. This B-cell depletion was well-tolerated by the patients, and there were no adverse effects from the rituximab treatment.
Conclusion: The authors suggest continued investigation of treating TED with rituximab; there should be a larger, placebo-controlled trial.
This trial did how that CAS scores decreased over the year-long follow-up, and this was apparently associated with the rituximab treatment. However, the efficacy of this treatment cannot be determined from this study, particularly because of the variable natural history of TED.
Commentary by Christian Nasr MD
Since Graves’ disease is a disease of the immune system causing disturbances in the thyroid gland and eye components, several pharmacological agents that target immune cells have been tried.
Glucocorticoids are the most commonly used agents in this paradigm; however, long-term treatment is needed and relapses often occur upon termination or tapering of the dose.
With the morbidity of prolonged courses of glucocorticoids, other “immunobiological” modalities have been looked at. Rituximab, a chimeric mouse-human monoclonal antibody that targets the CD20 antigen on pre-B and mature B lymphocytes and used mostly in lymphoid malignancies, has been looked at as a potential treatment for GO in several case reports. In this study, the authors enrolled 12 patients with significant disease and showed improvement with minimal side effects, making rituximab a potential treatment for GO.