Efalizumab to Treat Uveitis
This study examined the safety and potential efficacy of the monoclonal antibody efalizumab (Raptiva) for treating sight-threatening uveitis (eye inflammation). Efalizumab controls the activity of white blood cells called lymphocytes that cause inflammation. The drug is currently approved in the United States to treat patients with moderate to severe psoriasis.
Participants 18 and older with sight-threatening intermediate or posterior uveitis of at least 3 months duration, causing persistent macular edema in one or both eyes, were eligible for this study. The uveitis required treatment with at least 20 milligrams per day of prednisone, or the equivalent, or a combination of two or more anti-inflammatory treatments such as prednisone, methotrexate, cyclophosphamide, cyclosporine, etc.
Participants underwent the following tests and procedures:
- Medical history and physical examination.
- Weekly efalizumab treatment.
- Weekly eye examination, including measurement of vision and pressure in the eyes, dilation of the eyes and examination of the front and back parts of the eye.
- Weekly blood tests to measure the number and types of cells in the blood and to check for signs of inflammation and treatment side effects. At some visits, blood samples were collected to measure how much efalizumab remains in the blood and whether the body has developed an immune response to the medicine.
- Blood draw at enrollment and at 2 and 4 months for research tests to examine how participants' immune response was operating.
- Fluorescein angiography at enrollment and 1 and 3 months after enrollment, unless additional tests are needed, for medical management. This test checked for abnormalities of eye blood vessels. A yellow dye was injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina (the back portion of the eye) were taken with a special camera that flashes a blue light into the eye. The pictures show whether any dye has leaked from the vessels into the retina, indicating possible abnormalities.
- Monthly pregnancy test for women who could become pregnant.
Participants returned for treatment and clinic visits weekly for 16 weeks. After 16 weeks, participants whose macular edema had decreased and whose vision may have improved were offered to continue the injections.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Treatment of Non-Infectious Intermediate and Posterior Uveitis Associated Macular Edema With Humanized Anti-CD11a Antibody Therapy|
- Number of Participants With Systemic Toxicities, Adverse Events, or Infections [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]Safety outcomes were recorded by observing and tabulating the nature, severity and frequency of systemic toxicities, adverse events and infections throughout the study. Safety assessments were made by the investigators continuously during the study, with a review of the previous visit interval performed at each scheduled visit. Each participant was also encouraged to report any apparent adverse events between scheduled visits and could return for additional evaluations or treatment between scheduled visits if needed.
- Cystoid Macular Edema in the Worse Eye as Assessed by Optical Coherence Tomography (OCT). [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]Worse eye indicates the eye with the worst visual acuity (VA).
- Cystoid Macular Edema in the Better Eye as Assessed by Optical Coherence Tomography (OCT). [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]Better eye indicates the eye with better VA.
- Change in Visual Acuity in the Worse Eye From Baseline to 16 Weeks [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. This acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters the Snellen measurement is 20/20.
- Change in Visual Acuity in the Better Eye From Baseline to 16 Weeks [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. This acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters the Snellen measurement is 20/20.
|Study Start Date:||January 2006|
|Study Completion Date:||February 2009|
|Primary Completion Date:||February 2009 (Final data collection date for primary outcome measure)|
Participants who qualified for the study received weekly subcutaneous treatments of efalizumab, with the first dose being a test dose of 0.7 mg/kg and subsequent doses of 1 mg/kg (not to exceed 200 mg per dose), for a total treatment duration of 16 weeks.
Other Name: Raptiva
Background: Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects. Consequently, an effective treatment with a safer side effect profile is highly desirable.
Aims: This protocol evaluated the safety and potential efficacy of subcutaneous (SC) efalizumab (anti-CD11a) treatments for uveitis while reducing or eliminating standard medications commensurate with the standard of care. If the therapeutic benefit was sustained using the SC formulation, then maintenance therapy was continued as clinically indicated.
Methods: This was an open-label, non-randomized, clinical pilot study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00280826
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Robert Nussenblatt, MD, MPH||National Eye Institute (NEI)|