intravitreal adalimumab versus subcutaneous adalimumab in non-infectious uveitis

Conditions: Uveitis; Non-Infectious Uveitis

Summary: the objective of this study is to compare and evaluate the efficacy of subcutaneous (40mg) adalimumab biweekly injections to intravitreal adalimumab (1.5 mg/ 0.03 ml) administration, given at zero, 2 weeks then every four weeks, in subjects with active non-infectious intermediate-, posterior-, or pan-uveitis.

subject groups: 32 subjects will be enrolled in this study, 16 in each arm. they will be randomized to receive either 1.5 mg/ 0.03 ml of adalimumab by intravitreal injection or 40 mg of adalimumab subcutaneously at their first treatment visit and at the 2 weeks visit if eligible for a repeat injection. follow up will be every 2 days the first week then one week later and after that every 4-week intervals for total of 26 weeks. intervention details: * systemic adalimumab: subcutaneous injection of 40 mg adalimumab (humira) given every 2 weeks. * local adalimumab: intravitreal injection of 1.5mg/0.03ml adalimumab given at zero, 2 weeks, and then every 4 weeks. pre-treatment work up patients will undergo a comprehensive eye exam: * visual acuity, slit-lamp examination of the anterior segment, dilated fundus examination, electroretinography (erg) and fluorescein angiography (fa). * central macular thickness of all eyes will be measured with ocular coherence tomography before treatment. * purified protein derivative (ppd), complete blood count (cbc) and sgpt. post-injection follow-up * patients will be followed up every 2 days during the first week then one week later and after that every 4-week intervals. * on follow up visits, if deterioration in vision of two or more etdrs lines or worsening of ocular inflammation by more than 1+ cells/haze is detected at any visit, patients will be removed from the study and receive appropriate treatment. otherwise, if vision was stable or improved and/or inflammation is same or better, patients will be re-injected. * follow up is for 26 weeks. * oct and fluorescein angiography each visit. * erg will be performed at baseline and 26 weeks. * blood studies (cbc and sgpt) will be performed at baseline, 14 weeks and at 26 weeks. * injections would be delayed if a patient has an acute infection and would be given when it subsides.

Eligibility criteria:
inclusion criteria: * subject is ≥ 18 years of age. * subject is diagnosed with non-infectious intermediate-, posterior-, or pan-uveitis. * subject must have active disease at baseline as defined by the presence of at least 1 of the following parameters in at least one eye despite at least 2 weeks of prednisone ≥ 10 mg/day (or oral corticosteroid equivalent): * active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion * ≥ 1+ anterior chamber cells (standardization of uveitis nomenclature \[sun\] criteria) * ≥ 1+ vitreous haze (national eye institute \[nei\]/sun criteria) * subject with documented prior adequate response to oral corticosteroids (equivalent of oral prednisone up to 1 mg/kg/day). * if subject is on prednisone \>=10 mg (or corticosteroid equivalent) at baseline, the dose has not been increased or decreased in the past 14 days. * no increase in the immune modulatory therapy in the past three months * negative ppd test. * positive ppd test on anti tb medications. exclusion criteria: * subject with isolated anterior uveitis. * subject with confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to tb, cytomegalovirus, lyme disease, toxoplasmosis and herpes simplex virus (hsv). * subject with serpiginous choroidopathy. * subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial. * subject with corneal or lens opacities that preclude the evaluation of the vitreous haze. * subject with uncontrolled high intraocular pressure of ≥ 25 mmhg on maximal therapy. * subject with intermediate uveitis and symptoms and/or mri findings suggestive of a demyelinating disease such as multiple sclerosis. all subjects with intermediate uveitis must have had a prior brain mri at time of or after diagnosis of intermediate uveitis. * subject has received glucocorticosteroids implant (retisert®), or ozurdex within 6 months prior to baseline visit. * subject has received intraocular or periocular corticosteroids or intravitreal methotrexate within 90 days prior to baseline visit. * subject with proliferative or severe non-proliferative diabetic retinopathy. * subject with neovascular/wet age-related macular degeneration * subject with abnormality of vitreo-retinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) with the potential for macular structural damage independent of the inflammatory process. * subject with a systemic inflammatory disease and requires additional therapy with a systemic immunosuppressive agent at the time of study entry. * subjects with history of active or latent mycobacterium tuberculosis documented by purified protein derivative (ppd) and chest x-ray and not anti tuberculosis (tb) treatment.

Keywords: intravitreal adalimumab subcutaneous adalimumab