Efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis: a protocol for a multicentre, randomised, parallel three arms, active-controlled, phase III open label with blinded outcome assessment study.

INTRODUCTION: Non-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet. METHODS AND ANALYSIS: The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects' subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers. ETHICS AND DISSEMINATION: The protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation. TRIAL REGISTRATION NUMBER: 2020-000130-18; NCT04798755.

Levels of thrombopoietin in aqueous humor of patients with noninfectious acute anterior uveitis.

PURPOSE: To measure thrombopoietin (TPO) levels in the serum and aqueous humors of patients with noninfectious acute anterior uveitis. METHODS: A prospective, comparative, controlled study. Serum and aqueous humors were obtained from the eyes of 16 patients with noninfectious acute anterior uveitis. TPO levels were measured using an enzyme-linked immunosorbent assay (ELISA). The results obtained were compared with those of a control group. RESULTS: Serum concentrations of TPO were not significantly different between control individuals and patients with active anterior uveitis. Aqueous humor TPO levels were 54.46±16.24 pg/mL in the eyes of patients with uveitis, and 34.32±11.63 pg/mL in the eyes of controls. The difference between the two groups was significant (Mann-Whitney U-test for independent data, P=0.0008), with uveitis patients exhibiting significantly higher levels of TPO. CONCLUSION: The high levels of TPO in the aqueous humors of uveitis patients points toward a cytoprotective role of this factor in inflammatory repair processes and the recovery of tissue homeostasis.