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Rituximab aids refractory Graves' orbitopathy: small series shows success in off-label indication; benefits seen within 3 months of first infusion.

PARIS -- Rituximab seemed to be safe and effective for six patients with severe Graves' orbitopathy that was refractory to steroid therapy, Dr. Anna Mitchell reported at the congress.

But reports of the drug's use in this application are just beginning to emerge, she cautioned. "This is an off-label indication, and we must have randomized, controlled trial data to support this as an intervention."

Rituximab is used in treating rheumatoid arthritis and has recently been examined for possible benefit in other autoimmune disorders, including Graves' orbitopathy. The drug depletes circulating B cells, but does not interfere with precursor B cells or differentiated plasma cells, said Dr. Mitchell of Newcastle University, Newcastle upon Tyne, England.

She and her colleagues have used rituximab to treat six patients with refractory Graves' orbitopathy (one man, five women; ages 37-73).

Two of the six patients had dysthyroid optic neuropathy; one proved refractory to intravenous methylprednisolone and the other worsened despite orbital decompression surgery. The other four patients had been treated for severe Graves' orbitopathy that was refractory to multiple doses of methylprednisolone (4.5 g in three patients) or a combination regimen of methylprednisolone and mycophenolate mofetil (one patient).

All six patients received rituximab; the first three received two intravenous infusions of 1 g; the last three, infusions of 0.5 g. Infusions were scheduled 2 weeks apart; patients had to have absolute B-cell depletion confirmed before the second infusion could be administered.

At baseline, the patients' mean Graves' clinical activity score was 5.5 on a 10-point scale (range, 3-9). Within the first 3 months after the initial infusion, all patients saw an improvement in the CAS of at least 2 points.

One patient with dysthyroid optic neuropathy experienced an almost immediate, significant improvement in visual acuity; within 10 days of the first infusion, this patient's vision went from perception of light only to 6/18, a metric rating that corresponds to 20/60 on the visual acuity scale.

The other patient with dysthyroid optic neuropathy did not experience any improvement in visual acuity within 12 days of her first infusion, and so opted for an emergency orbital decompression.

Dr. Mitchell added that there was no difference in efficacy between the 1-g and 0.5-g doses, but did mention the cost savings associated with the lower dose.

In January 2010, researchers from the University of California, Los Angeles, published another case series of six patients who had refractory Graves' orbitopathy and underwent treatment with rituximab.

Dr. Dinesh Khanna and colleagues administered rituximab in two infusions of 1 g each, given 2 weeks apart. In their case series, all the patients had a significant improvement in the CAS. The four patients with dysthyroid optic neuropathy experienced significant improvements in visual acuity within 4 weeks of the initial infusion, and stabilized at pre-neuropathy levels by 2 months (Ophthalmology 2010;117:133-9).

However, proptosis remained unchanged in all, and no patient showed improvement in extraocular motility.

Dr. Mitchell did not present specific adverse event data. However, the California study noted that one patient developed a urinary tract infection, one had an exacerbation of preexisting hypertension, and one died of sudden cardiac arrest at 3 months after the final infusion.


Major Finding: At baseline, mean Graves' clinical activity score was 5.5 on a 10-point scale (range, 3-9). Within the first 3 months after the initial rituximab infusion, all patients saw an improvement in the CAS of at least 2 points.

Data Source: Six patients with severe Graves' orbitopathy that had been refractory to steroid treatments.

Disclosures: Dr. Mitchell had no relevant financial disclosures.


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Title Annotation:ENDOCRINOLOGY
Author:Sullivan, Michele G.
Publication:Internal Medicine News
Article Type:Report
Geographic Code:4EUFR
Date:Dec 1, 2010
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