Comparative Efficacy and Safety of Tocilizumab Versus Adalimumab in Severe Uveitis Associated with Behçet’s Disease: A Multicenter Randomized Trial

The primary objective of this study is to assess the benefit of **tocilizumab** compared to **adalimumab** in treating sight-threatening uveitis associated with Behçet’s disease at week 16. This is clinically relevant as it aims to determine the more effective treatment option for managing severe ocular inflammation, potentially improving patient outcomes and preserving vision.

Secondary objectives include:

• Estimating and comparing the change in best corrected visual acuity (BCVA).
• Assessing the time to complete remission at various intervals (weeks 4, 8, 12, 24, 36, and 48).
• Evaluating and comparing the safety profiles of **adalimumab** and **tocilizumab**.
• Assessing changes in macular edema and other signs of ocular inflammation.
• Evaluating the effect on retinal vessel leakage and steroid sparing.
• Comparing the change in ocular inflammation in the anterior chamber.
• Evaluating the number and time to relapse of uveitis and the characteristics of uveitis at worsening.
• Assessing the time to treatment failure based on specific ocular criteria.
• Estimating the effect on extra ophthalmologic manifestations of Behçet’s Disease.
• Comparing the mean change in SF-36 quality of life and Behçet’s Disease Quality of Life Measure.
• Estimating changes in Behçet’s Disease Current Activity Form and Behçet’s Syndrome Activity Score.

The clinical trial focuses on participants diagnosed with **severe uveitis** associated with Behçet’s disease. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a diagnosis of Behçet’s disease according to the International Criteria for Behçet's Disease (ICBD) and must exhibit non-infectious intermediate, posterior, or pan-uveitis in at least one eye. The trial does not involve a vulnerable population. Participants must be affiliated with a social security system and provide written informed consent. Relevant lifestyle considerations include the requirement for female subjects of child-bearing potential to have a negative serum pregnancy test and for all subjects with reproductive potential to use adequate contraceptive measures during the study and for a specified period after therapy. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed as a **randomized**, double-blind, controlled study to evaluate the efficacy and safety of **adalimumab** compared to **tocilizumab** in patients with severe uveitis associated with Behçet’s disease. The trial will span a period of approximately four years, with an estimated recruitment start date in April 2024 and an anticipated end date in April 2028. Participants will be randomly assigned to receive either **adalimumab** or **tocilizumab**, both administered via subcutaneous injection. The primary objective is to assess the benefit of **tocilizumab** relative to **adalimumab** in achieving complete remission of ocular involvement by week 16, with a prednisone dose of 5 mg/day or less.

The study will include several key visits: an initial screening visit, regular follow-up visits, and an end-of-study visit. During the screening visit, eligibility will be confirmed based on criteria such as age, diagnosis of Behçet’s disease, and absence of active tuberculosis or malignancy. Participants will also provide informed consent at this stage. Follow-up visits will occur at weeks 4, 8, 12, 16, 24, 36, and 48, during which efficacy and safety assessments will be conducted, including measures of corticosteroid sparing, acute-phase reactants, and changes in visual acuity and retinal thickness. The end-of-study visit will finalize data collection and assess long-term outcomes.

Participant involvement is expected to last up to 48 weeks, with conditions for early termination including significant adverse events, withdrawal of consent, or non-compliance with study protocols. The trial will adhere to rigorous ethical standards, ensuring that all procedures are conducted in accordance with regulatory requirements and guidelines. The study aims to provide valuable insights into the comparative effectiveness of these biologic agents in managing severe uveitis in Behçet’s disease, potentially informing future therapeutic strategies.

The clinical trial involves the administration of **RoActemra**, a pharmaceutical product containing the active substance **tocilizumab**. RoActemra is provided as a **solution for injection** in a pre-filled syringe, with a concentration of 162 mg. The medication is administered via **subcutaneous use**. The maximum daily dose is 162 mg, with a total maximum dose of 2430 mg over a treatment period of 15 weeks. Tocilizumab is a protein-based therapeutic agent, classified under the ATC code L04AC07. The product is manufactured by Roche Registration GmbH and is not formulated for pediatric use.

Another treatment used in the trial is **Humira**, which contains the active substance **adalimumab**. Humira is available as a **solution for injection** in a pre-filled pen, with a dosage of 80 mg. The administration route is also **subcutaneous use**. The maximum daily dose for adalimumab is 40 mg, with a total maximum dose of 800 mg over a 15-week treatment period. Adalimumab, like tocilizumab, is a protein-based therapeutic agent and is classified under the ATC code L04AB04. This product is manufactured by AbbVie Deutschland GmbH & Co. KG and is not intended for pediatric use.

Both treatments are being evaluated for their efficacy and safety in managing severe uveitis associated with Behçet’s disease. The trial aims to compare the benefits of tocilizumab against those of adalimumab over a 16-week period. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints related to the treatment of severe uveitis in Behçet’s disease. The primary endpoint is defined as the complete remission of ocular involvement with a prednisone (or prednisolone, if prednisone is unavailable) dosage of 5 mg/day or less at week 16 after randomization. Complete remission is characterized by the resolution of retinal vasculitis and/or macular edema under the specified prednisone dosage.

Secondary endpoints include various measures such as corticosteroid sparing, with targets set at less than 0.1 mg/day/kg of prednisone, and the mean and cumulative doses at week 16. Additional assessments involve the time to response onset, changes in acute-phase reactants like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at multiple timepoints (weeks 4, 8, 12, 16, 24, 36, and 48), and the rate and time to occurrence of relapse or worsening of the disease. Relapse is defined by the reappearance of clinical or paraclinical features of active disease or the emergence of new lesions.

Further evaluations include changes in the Behçet’s Disease Current Activity Form (BDCA) and Behçet’s Syndrome Activity Score (BSAS) at specified weeks, as well as changes in other organs affected by Behçet’s disease. Quality of life assessments will be conducted using the SF36v2 Health Survey and the Behçet’s Disease Quality of Life Measure (BD-QoL) at weeks 16 and 24. Safety and tolerability will be monitored through the frequency and severity of adverse clinical events at various intervals throughout the study.

Additional parameters include changes in Tyndall, flare, and Vitreous Haze, best corrected visual acuity (SNELLEN score), and central retinal thickness measured with Optical Coherence Tomography (OCT) at multiple timepoints. The percentage of patients with central retinal thickness less than 300 microns and those without retinal vessel leakage on retinal angiography will also be evaluated at specified weeks.