March 2010

 

OPHTHALMOLOGY NEWS

 

Hopeful prognosis for Graves’ treatment


by Maxine Lipner Senior EyeWorld Contributing Editor

   

Rituximab combats inflammatory disease components

Rituximab may help to decrease some of the symptoms associated with Graves’ disease, including inflammation and optic neuropathy, although bulging of the eyes was unaffected Source: Raymond S. Douglas, M.D., Ph.D.

For patients with Graves’ disease the drug rituximab (Rituxan, Genentech, South San Francisco, Calif.) can decrease inflammation and help to wean patients off steroids, according to Raymond S. Douglas, M.D., Ph.D., associate professor of ophthalmology, Kellogg Eye Center, University of Michigan, Ann Arbor. In a recent study published in the October 2009 issue of Ophthalmology, a small group of patients with recalcitrant disease experienced improvement of symptoms after treatment with rituximab.

Investigators decided to look into rituximab for Graves’ disease after noting that the drug had been effective against a similar type of condition—rheumatoid arthritis. “Much of our research has shown that Graves’ disease has many of the same molecular mechanisms as rheumatoid arthritis,” Dr. Douglas said. “Rituximab is becoming the drug of choice for rheumatoid arthritis and has become much more effective than people anticipated.” Because Graves’ disease is largely an antibody-driven disease very similar to rheumatoid arthritis, investigators thought that it would be very reasonable to try rituximab here.

The drug already showed promise in some related work. “There have been a couple of preliminary efforts done also demonstrating that rituximab may be effective in treating hypothyroidism,” Dr. Douglas said. “The other aspect of rituximab is that it has a relatively low side effect profile and has been used for long enough to actually understand that side effect profile.” As a result, investigators felt that trying rituximab would be natural here. “As an immunologic treatment it seemed logical that it would be effective. At least we understood its limitations and potential side effects.”

Recalcitrant case series

In the retrospective interventional case series, six steroid-resistant patients with vision threatening disease were given rituximab treatment. “These patients had been treated with steroid therapy for the prior several months without improvement,” Dr. Douglas said. “They were then given two doses of rituximab and their clinical course was followed.”

Investigators found the drug to be promising. “We were surprised that rituximab dramatically decreased the inflammation associated with the disease and dramatically improved their signs and symptoms,” Dr. Douglas said. “Within 2-3 weeks of starting the drug we could taper them off of the steroid that they had been taking for up to six months prior without any type of recurrence.”

In addition, they found that there was improvement of signs and symptoms. “In several of the patients the optic neuropathy, the vision that they were beginning to lose, reversed after taking rituximab,” Dr. Douglas said. “The reversal was dramatic; the severity of their disease was about six on a seven-point scale and within about two to three weeks it was reduced to a two.” Dr. Douglas said this kind of reduction is not seen in almost any type of therapy. However, certain ocular signs of the condition remained unchanged. “The drug did not decrease the bulging of the eyes and some of the double vision, which didn’t really surprise us,” Dr. Douglas said. There were no ocular complications associated with the rituximab.

Long-lasting effect

Dr. Douglas sees rituximab as a potentially very effective therapy. “The mechanism of action appears to be very different than steroid therapy,” he said. “It appears to be targeting the inflammatory reactions that are going on in these patients and it still leaves open the possibility for other drugs that might inhibit the fibrotic components.” He thinks that the use of this therapy could be potentially broadened. “It appears to have a relatively low side effect profile,” he said. “In fact, it is probably much less than that of chronic steroids.”

He theorizes that rituximab is working to effectively control the inflammatory component of the disease. “Steroids attack the inflammation and sometimes you can see temporary improvement, but once you stop the steroids they don’t appear to have any impact on the natural history of the disease and the inflammation usually comes right back,” Dr. Douglas said. “With rituximab, we gave it in two doses and then the patients went into remission.” None of the inflammatory signs of the condition have yet recurred. Dr. Douglas is hopeful that the drug may have even more far reaching effects in the right patients. “If we could identify patients who had severe disease or who were going to eventually develop severe disease, could we give the drug earlier in the process and prevent some of those downstream things from happening?” he asked. “We don’t know yet, but that would be one of the major areas of study for future investigations.”

Editors’ note: Dr. Douglas has no financial interests related to his comments.

Contact information

Douglas: 734-936-0946, Raydougl@med.umich.edu

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