Golimumab for the Treatment of Refractory Behcet's Uveitis

Efficacy and Safety of Golimumab in the Treatment of Refractory Uveitis in Patients With Behcet's Disease

The aim of this single-center prospective study is to evaluate the efficacy and safety of Golimumab （GOL）, fully humanized anti-tumor necrosis factor (TNF)-α monoclonal antibody, in the treatment of refractory Uveitis of Behçet's disease (BDU), to verify its effects on decreasing the dose of cortical steroids, and to determine whether it can reduce BDU recurrence.

Study Overview

• Status: Terminated
• Conditions: Behcet Syndrome; Uveitis
• Intervention / Treatment: Biological: Golimumab (GOL)

Detailed Description

Uveitis of Behçet's disease (BDU) is the most common form of ocular manifestations, which is also the leading cause of irreversible visual impairment. The aim of the study is to improve the treatment strategy of the disease as well as to reduce blindness.

Monoclonal anti-TNF antibodies were recommended in 2018 recommendations for treating eye involvement affecting the posterior segment (level of evidence: IIA; strength of recommendation: B), Infliximab was mentioned for the treatment of initial or recurrent episode of acute sight-threatening uveitis.

Golimumab （GOL）is a fully-humanized anti-TNF-α monoclonal antibody, retrospective study on non-infectious uveitis and BDU has obtained promising results.

This single-center prospective study is to evaluate the efficacy and safety of GOL in the treatment of refractory BDU, to verify its effects on tapering the dose of corticosteroids, and to determine whether it can reduce BDU recurrence. We aim to enroll nine refractory BDU patients with acute onset posterior uveitis, with difficulty tapering corticosteroids while being treated with at least one of the commonly used immunosuppressants.

All participants will receive GOL monthly for six months, oral immunosuppressants will remain unchanged. During follow-up, intraocular inflammation status, BCVA, as well as extraocular manifestations, will be recorded. The primary endpoints are the efficacy of the first dose of GOL, and the recurrence of uveitis after 12 months of treatment. Secondary endpoints other than intraocular inflammation will be achieved on each follow-up visit, as the quality of life improvements, side effects, recurrence of uveitis, and corticosteroids-tapering effects.

On statistical analysis, the self-control treatment efficiency and recurrence rate difference will be determined using T-test of paired samples at a significance level of 0.05(2-sided).

To ensure the interest of the participants, our study has been reviewed by the ethics committee, and drug clinical research liability insurance was prepared.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jinjing Liu, M.D.; Phone Number: +8613581605769; Email: questionmark003@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All participants fulfill the proposed International Criteria for BD, either ISG (International Study Group) criteria(1990) or ICBD(International Conference on Behcet's Disease) criteria(2013).
• All participants present with refractory BDU, acute onset uveitis, either posterior segment involvement or panuveitis, with difficulty tapering corticosteroids while being treated with at least one of the commonly used immunosuppressants, without severe extraocular manifestations.

Exclusion Criteria:

• Patients with impaired hepatic and renal function, other severe ocular diseases, active tuberculosis, viral hepatitis, malignancy, pregnancy, congestive heart failure, or had biologics treatment within three months will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Golimumab for refractory BDU; This study is a self-control study and all the participants will be enrolled in the interventional arm.	Biological: Golimumab (GOL); Patients with refractory BD associated uveitis will receive Golimumab therapy, the efficacy and corticosteroids-sparing effects will be evaluated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Golimumab on BD Uveitis	Efficacy of Golimumab based on Behçet's disease ocular attack score 24 （BOS24）	four weeks
Efficacy of Golimumab on BD Uveitis	Efficacy of Golimumab based on Best corrected visual acuity(BCVA)	four weeks
Efficacy of Golimumab on BD Uveitis	Efficacy of Golimumab based on Optical Coherence tomography(OCT)).	four weeks
Difference of recurrence rate before and after intervention	Difference of recurrence rate of uveitis before and after 12 months of GOL treatment	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraocular inflammation evaluation BOS24 index	Visual acuity, anterior chamber cells, vitreous opacities, retinal inflammation, macular thickness, etc.	each follow-up visit / every four weeks, up to six months
Corticosteroid-tapering effects	Corticosteroid will be tapered to minimum dose(Prednisone 5-10mg/d) within four months during the course of GOL treatment.	six months
Changes of uveitis recurrence	Changes of recurrence rate before and after six months of GOL treatment.	six months
Severity of uveitis on recurrence	Differences of severity of recurrence before and after treatment, measured by BOS24.	six months
Severity of uveitis on recurrence	Differences of severity of recurrence before and after treatment, measured by , BCVA.	six months
Severity of uveitis on recurrence	Differences of severity of recurrence before and after treatment, measured by OCT.	six months
Impact on quality of life	Record quality of life on questionnaire, BehÇet's disease current activity form 2006（BDCAF2006）.	each follow-up visit / every four weeks, up to six months
Impact on quality of life	Record quality of life on questionnaire, short from Health Survey(SF-36).	each follow-up visit / every four weeks, up to six months
Side effects of treatment	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	six months

Collaborators and Investigators

• Sponsor: Wenjie Zheng
• Investigators: Principal Investigator: Wenjie Zheng, M.D., Department of Rheumatology, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2020
• Primary Completion (Actual): December 15, 2022
• Study Completion (Actual): December 15, 2022

Study Registration Dates

• First Submitted: December 8, 2019
• First Submitted That Met QC Criteria: January 2, 2020
• First Posted (Actual): January 6, 2020

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: April 5, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Eye Diseases; Genetic Diseases, Inborn; Stomatognathic Diseases; Mouth Diseases; Uveitis, Anterior; Panuveitis; Uveal Diseases; Vasculitis; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Skin Diseases, Vascular; Behcet Syndrome; Uveitis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Tumor Necrosis Factor Inhibitors; Golimumab
• Other Study ID Numbers: GOL-BDU-PUMCH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No