Biologics or radiotherapy?

March 15, 2011

No single intervention for inflammatory thyroid eye disease currently provides a cure.

Chicago-No single intervention for inflammatory thyroid eye disease currently provides a cure. Available therapies remain palliative, targeting only a section of a complex immunologic cascade.

While awaiting development of more effective therapies, clinicians need to tailor their treatment to the individual as well as consider ways to prevent the condition or prevent progression.

With no evidence-based gold standard for treatment, clinicians may have a preference for medical therapy or radiotherapy. In a program at oculofacial plastic surgery subspecialty day during the annual meeting of the American Academy of Ophthalmology, Rona Z. Silkiss, MD, FACS, and Peter J. Dolman, MD, FRCSC, assessed the advantages and disadvantages of these approaches as well as future interventions.

"Biologics are the best technology available with the potential to deliver targeted therapy with the fewest side effects. In the not-too-distant future, targeted novel biologics will prove radiotherapy to be primitive and obsolete," said Dr. Silkiss, who is also associate clinical professor of ophthalmology, University of California, San Francisco.

She explained that biologics are the preferred therapy because of the pathophysiology of thyroid eye disease, in which eye muscles, connective tissue, and fat are infiltrated by lymphocytes and are the target of acute inflammation.

Clinicians often face a dilemma when patients have not had a response following one or more treatments with intravenous or oral steroids. Options include another course of treatment with IV or oral biologics, combined with radiotherapy, or consideration of novel biologics such as rituximab (Rituxan, Genentech).

According to Dr. Silkiss, biologics provide a favorable response rate. The combined success rate for oral and IV steroids is 64%; with added radiotherapy, the success rate increases by about 6%. To date, the success rate of rituximab is 98%.

Presenting information on the effectiveness of orbital radiotherapy, Dr. Silkiss reviewed the results of an ophthalmic technology assessment of this approach for Graves ophthalmology in which researchers evaluated five observational and nine randomized studies. None of the sham-controlled, randomized studies demonstrated efficacy for proptosis or soft tissues changes, although two demonstrated improved vertical range of motion. Three of the five observational studies had favorable outcomes, but the success rates varied widely, from 40% to 97%.

"The conclusion of the ophthalmic technology assessment group was that orbital radiation has a very limited role in treating non-sight-threatening thyroid eye disease. The effect may be limited to improving or halting progression of ocular dysmotility alone, and in fact it was unclear whether this improved motility translated into enhanced functioning or quality of life," Dr. Silkiss said.