Efalizumab to Treat Uveitis
Condition: Uveitis; Macular Edema
MeSH terms: Macular Edema; Uveitis; Edema
Intervention: Efalizumab
Intervention description: 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.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: OCT; Retinal Disease; Adhesion Molecule; Ocular Inflammation; Raptiva; Macular Edema; Uveitis; Immunosuppression

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant is 18 years of age or older;

          -  Participant has a diagnosis of sight-threatening, intermediate or posterior uveitis of
             at least three months duration prior to original enrollment that is causing persistent
             cystoid macular edema in one or both eyes. Their disease requires treatment to control
             their intraocular inflammatory disease with at least 20 mg/day of prednisone (or
             equivalent) or any combination of two or more anti-inflammatory treatments for
             uveitis, including for example prednisone, cyclophosphamide, cyclosporine,
             azathioprine, mycophenolate mofetil, methotrexate, etc.

          -  Participant exhibits intolerance to the indicated systemic medications required for
             their uveitis or, though their uveitis may be under control, wish to be taken off
             their present medications due to potential or actual unacceptable side effects.

          -  Participant has visual acuity in at least one eye of 20/200 or better.

          -  Participant has normal renal or liver function or no worse than mild abnormalities as
             defined by the Common Toxicity Criteria.

          -  Participant is not currently pregnant or lactating.

          -  Both men and women with reproductive potential and who are sexually active agree to
             use acceptable birth control methods throughout the course of the study and for six
             weeks following the last administration of the study medication.

          -  Participant must have the ability to understand and sign an informed consent form.

        Exclusion Criteria:

          -  Participants who had received previous treatment with an intercellular adhesion
             molecule (ICAM) or lymphocyte function-associated antigen-1 (LFA-1) directed
             monoclonal antibody or any other investigational agent that would interfere with the
             ability to evaluate the safety, efficacy or pharmacokinetics of efalizumab.

          -  Participant has a significant active infection.

          -  Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed
             within the past 5 years.