Co-THEIA (Combination THerapy with mEthotrexate and adalImumAb for uveitis): Efficacy, safety and cost-effectiveness of methotrexate, adalimumab, or their combination in non infectious non anterior uveitis: a multicenter, randomized, parallel 3 arms, active-controlled, phase 3 open label with blinded outcome assessment study

INTERVENTION: Product Name: Adalimumab Pharmaceutical Form: Solution for injection INN or Proposed INN: ADALIMUMAB CAS Number: 331731‐18‐1 Product Name: Methotrexate Pharmaceutical Form: Tablet INN or Proposed INN: METHOTREXATE Other descriptive name: METHOTREXATE SODIUM CONDITION: Non infectious non anterior uveitis Therapeutic area: Diseases [C] ‐ Eye Diseases [C11] PRIMARY OUTCOME: Main Objective: To compare the proportion of patients achieving a Good Clinical Response by week 16 that is maintained in every study visit until week 52. Primary end point(s): To compare the proportion of patients achieving a Good Clinical Response by week 16 that is maintained in every study visit until week 52. Secondary Objective: To compare the clinical components of the Good Clinical Response variable between treatment strategies (see page 71 for a complete list of the components); To compare the proportion of patients achieving a Good Clinical Response by week 16; To compare several Patient Reported Outcomes Measures (health‐ and vision‐related quality of life, anxiety and depression) between treatment strategies; To compare the time to relapse after week 16 between treatment strategies; To assess the safety of each treatment strategy; To assess the cost‐utility and cost‐effectiveness from both a Health System and a Societal perspectives of the combination therapy and the ADA monotherapy compared with MTX given alone; To identify genetic and proteomic biomarkers associated with drug response to each treatment strategy. Timepoint(s) of evaluation of this end point: 52 weeks SECONDARY OUTCOME: Secondary end point(s): To compare the clinical components of the Good Clinical Response variable between treatment strategies (see page 71 for a complete list of the components); To compare the proportion of patients achieving a Good Clinical Response by week 16; To compare several Patient Reported Outcomes Measures (health‐ and vision‐related quality of life, anxiety and depression) between treatment strategies; To compare the time to relapse after week 16 between treatment strategies; To assess the safety of each treatment strategy; To assess the cost‐utility and cost‐effectiveness from both a Health System and a Societal perspectives of the combination therapy and the ADA monotherapy compared with MTX given alone; To identify genetic and proteomic biomarkers associated with drug response to each treatment strategy. Timepoint(s) of evaluation of this end point: 52 weeks INCLUSION CRITERIA: 1. Subjects diagnosed with non‐infectious intermediate‐, posterior‐, or pan‐uveitis in at least one eye; 2. Adult patients (=18 years); 3. Subjects with at least one flare of active eye inflammation in the previous 180 days before Baseline visit, defined by the presence of at least 1 of the following parameters in either eye: a. Active chorioretinal or retinal vascular lesion, AND/OR b. Presence of macular edema by optical coherence tomography (OCT: thickness >350 µm AND cysts or intraretinal fluid), AND/OR c. = 2+ anterior chamber cells , AND/OR d. = 2+ vitreous haze 4. Subjects with active eye inflammation at Baseline visit, defined by the presence of at least 1 of the following parameters in either eye: a. Active chorioretinal or retinal vascular lesion, AND/OR b. Presence of macular edema by OCT (thickness >350 µm AND cysts or intraretinal fluid), AND/OR c. = 1+ ACC, AND/OR d. = 1+ vitreous haze. Are the trial subjects