Article Date: 7/1/2009

A Sense of Humira
CLINICAL TRIAL SPOTLIGHT

A Sense of Humira

A drug approved for rheumatoid arthritis is being tested for uveitis.

ANDREW E. MATHIS, PhD, MEDICAL EDITOR

Rheumatoid arthritis (RA) afflicts roughly 2.5 million Americans. Unlike osteoarthritis, RA has a distinct autoimmune component that causes the disease to affect not only the joints, but several other parts of the body, including the eye.

Adalimumab (Humira, Abbott Laboratories) was approved in December 2002 for the treatment of RA and has subsequently been shown to be effective for other inflammatory diseases, some of which can affect the eye, including Crohn disease and juvenile idiopathic arthritis. Now the drug is being put through a clinical trial to test one of the most common ocular complications of such diseases — uveitis.

The trial, being undertaken at the Oregon Health and Science University in Portland, as well as Cleveland Clinic and the University of Illinois-Chicago, is an open-label, single-group-assignment treatment study aimed at refractory, noninfectious uveitis. Eric B. Suhler, MD, MPH, an ophthalmologist at Oregon Health and Science, discussed the study with Retinal Physician.

THE ROLE OF IMMUNOMODULATION

Besides being approved for RA and two other varieties of arthritis, adalimumab has also received approval for the treatment of psoriasis and Crohn disease. Asked what these disorders have in common with uveitis, Dr. Suhler responded, "These diseases have in common the fact that they are all putatively autoimmune diseases, which we consider to be diseases brought about by a combined immunogenetic predisposition and an unknown triggering stimulus. As such, immunomodulation therapy is used to treat all of these diseases, including uveitis, although owing to the relatively uncommonness of inflammatory eye diseases, large studies leading to FDA approval for immunomodulators in uveitis has been somewhat less common than with these other diseases."

So immunomodulation would seem to the key to treating uveitis. Adalimumab affects this result by blocking the activity of tumor necrosis factor (TNF)-α, which is a key cytokine in the initiation and propagation of the immune response and resulting inflammation. "By blocking this cytokine," Dr. Suhler said, "significant anti-inflammatory effects may be realized."

WHY THIS FOCUS?

Since inflammation is ultimately the target of adalimumab in this trial, it is not surprising that other drugs that inhibit TNF-α have been tested for ocular disease. Adalimumab is the third drug that inhibits TNF-α to be approved for use in the United States. The first two were infliximab (Remicade, Johnson & Johnson) and etanercept (Enbrel, Wyeth). Etanercept is in a phase 3 trial for uveitis secondary to juvenile RA, while infliximab is in several trials for a number of eye diseases, including AMD and diabetic macular edema, as well as childhood uveitis.

Of greater interest here, however, is a Lebanese trial testing adalimumab on diabetic retinopathy and CNV. "There have been reports of other TNF-α blockers being used to treat CNV, due to the presumed inflammatory component to CNV pathophysiology," Dr. Suhler said. "Inflammation is a key mediator in many diseases and we continue to learn more about this."

RESULTS THUS FAR

Initial results of this trial were presented in May at the annual meeting of the Association for Research in Vision and Ophthalmology, held in Fort Lauderdale, FL. At that meeting, Dr. Suhler presented 10-week results on 16 patients, 11 of whom were showing preliminary evidence of benefit from therapy with adalimumab. While longerterm results are further off, Dr. Suhler is confident that adalimumab will have a use in treating uveitis, even when the ocular inflammation is not a result of RA. "We consider uveitis to be an autoimmune disorder in its own right," Dr. Suhler said, indicating that adalimumab may emerge as a therapy for primary uveitis. RP



Retinal Physician, Issue: July 2009