Rituximab offered no therapeutic benefit in Graves’ ophthalmopathy

SAN JUAN, Puerto Rico — In a randomized, double blind, placebo-controlled trial, rituximab did not clinically improve Graves’ ophthalmopathy and had a 50% success/failure rate in patients with the disease.

“In patients with active, moderate-to-severe, progressive Graves’ ophthalmopathy, for approximately 1 year duration, rituximab does not offer a therapeutic benefit,” Marius N. Stan, MD, of the Mayo Clinic in Rochester, Minn., said. “The other side is 50% of patients improved in both groups.”

Stan and colleagues used a clinical activity score (CAS) that took into consideration spontaneous retrobulbar pain, pain with eye movement, redness of the eyelids, redness of the conjunctiva, swelling of the eyelids, inflammation of the caruncle and conjunctival edema.

Marius N. Stan

The study enrolled 25 patients with active moderate-to-severe Graves’ ophthalmopathy, separated smokers from nonsmokers and, subsequently, split those along their baseline CAS scores. The researchers then randomly assigned patients in the small groups to rituximab (Rituxan, Genentech; n=13) or placebo (n=12). Researchers reevaluated CAS ocular parameters, thyroid and immune parameters, CT of the orbits, quality of life and, optionally, cytokines at baseline, week 8, week 16, week 24 and week 52. Twenty-one patients continued through the primary endpoint of 6 months, and 19 continued on through 52 weeks.

At 24 weeks, change in CAS was 1.8 (1.8 [standard deviation]) in the placebo group and 1.2 (2.0 SD) in the rituximab group. CAS also increased in two patients receiving rituximab. At the 52-week endpoint, six patients in each group had less than two-point decreases in CAS, indicating treatment failure. Four patients — three in the rituximab group and one in the placebo group — experienced disease progression, Stan said.

In addition, Stan said there was no difference in the quality of life measures between the treatment and placebo groups.

Moderate-to-severe adverse events were seen in five patients in the rituximab group, as compared with one patient in the placebo group.

“Basically, the groups were identical in their quality of life at baseline and at 24 weeks, with minimal improvement between these time points,” he said. – by Katrina Altersitz

For more information:

Stan MN. Highlighted Oral Abstract 3. Presented at: the 83rd Annual Meeting of the American Thyroid Association; Oct. 16-20, 2013; San Juan, Puerto Rico.

Disclosure: Stan reports no relevant financial relationships. This study was supported by the NIH.