Outcome of Treatment of Uveitis With Biologic Drugs in Resistant Cases Vogt-koyanagi-Harada Disease

Uveitis Clinical Trial

Official title:

Outcome of Treatment of Uveitis With Biologic Drugs in Resistant Cases Vogt-koyanagi-Harada Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05349747
• Other study ID #: Uveitis
• Status: Not yet recruiting
• Start date: April 30, 2022
• Est. completion date: August 2024

Study information

• Verified date: April 2022
• Source: Assiut University
• Contact: salma Safwat
• Phone: +201022691820
• Email: Salmahafez91[@]outlook.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

• Reviewing the characteristics of patients with uveitis caused by Vogt-Koyanagi-Harada Syndrome treated at Assiut University Hospital at the Department of Ophthalmology and Department of Rheumatology, Physical Medicine, and Rehabilitation including the ocular features in terms of uveitis location, type and complications and systemic features of those subjects who showed an inadequate response to conventional immunomodulatory drugs.

• Assess the results of treatment with biologic drugs, including rates of failure and adverse events. This will help uveitis specialists to reach a conclusion about the best treatment protocols for Uveitis in Vogt-Koyanagi-Harada Syndrome in our population in terms of safety, efficacy, and cost-effectiveness.

Description:

Uvea (Latin for grape) is the middle vascular coat of the eyeball. Strictly speaking, uveitis is defined as inflammation of the uvea, but often the inflammatory process involves adjacent intraocular structures e.g. the anterior chamber, the vitreous humor, or the retina. Inflammation in the uvea can be due to infections, masquerades such as B-cell lymphoma, or immune-mediated diseases.

Vogt-Koyanagi-Harada syndrome is a systemic autoimmune disease characterized by bilateral, chronic, diffuse granulomatous panuveitis in addition to neurological, auditory, and integumentary manifestations. These manifestations are variable and race dependent.

This inflammatory syndrome is probably the result of an autoimmune mechanism, influenced by genetic factors, and appears to be directed against melanocytes. On histopathologic examination, typical cases show non-necrotizing diffuse granulomatous panuveitis with initial sparing and late involvement of the choriocapillaris and formation of Dalen-Fuchs' nodules. Fluorescein angiography, lumbar puncture, and echography are useful adjuncts in the diagnosis and management of VKH syndrome. Patients with this syndrome are treated generally with high dose systemic corticosteroids, immunomodulatory agents such as cyclosporine, or more recently biological response modifiers which are used as steroid-sparing agents to minizeminimize side effects of long term steroid use.

Since their discovery in the 1990s, biologic drugs have been used to treat uveitis refractory to traditional immunosuppressants. Many questions on their use though have remained unanswered; particularly when to initiate therapy, which agent and at what dosage to use, and for how long the treatment should continue.

The Biologic Response Modifiers represent the future of therapy in immune-mediated uveitis. Biological anti-inflammatory agents (for example antagonists of tumor necrosis factor alpha-like Infliximab and adalimumab) are also showing very promising results.

Biologics alone or combined with conventional therapies are used in refractory cases of Uveitis. Biologics reported for use in uveitis interferon alpha 2a (IFN-α 2a); anti-tumor necrosis factor (TNF) agents-infliximab and adalimumab; anti-interleukins (IL)-tocilizumab, secukinumab (in most of the published papers, this biologic has failed to demonstrate the ability to control uveitis when compared to placebo) and gevokizumab; anti-CD20-rituximab and anti-CD 25-daclizumab.

In many cases, these agents will be seen listed as the first choice in some autoimmune diseases, depending on the patient's history, age, sex, type and severity of the inflammatory disease, etc. The interdisciplinary treatment between ophthalmologists and rheumatologist is essential to initiate and monitor these therapies. Follow-up visits of subjects with uveitis should be aimed to determine the evolution of inflammatory signs until their complete resolution, thus ensuring the least possible consequences.

The most common side effects are localized site reactions (pain, erythema, and rash). other side effects include upper respiratory tract infections, urinary tract infections, cough, rash, back pain, nausea, vomiting, abdominal pain, headache, weakness, and fever. Other noted side effects include low or high blood pressure, chest pain, difficulty breathing, rash, itching, fever, and chills.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: August 2024
• Est. primary completion date: April 2024
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Uveitis with clinical features of Vogt-Koyanaga-Harada Syndrome.

2. A follow-up and assessment at least twelve months from the start of treatment.

Exclusion Criteria:

• Exclusion of other infectious and non-infectious uveiticuveitis etiologies that may mimic the given clinical presentation of autoimmune uveitis;

• The presence of contraindication to treatment with biologic drugs e.g. active or latent tuberculosis, viral hepatitis and demyelinating diseases.

Related Conditions & MeSH terms

• Uveitis
• Uveomeningoencephalitic Syndrome

Intervention

Biological:
• Biologic drugs
Assess the results of treatment with biologic drugs

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (5)

Fang W, Yang P. Vogt-koyanagi-harada syndrome. Curr Eye Res. 2008 Jul;33(7):517-23. doi: 10.1080/02713680802233968. Review. Erratum in: Curr Eye Res. 2008 Sep;33(9):812.. — View Citation

Hatemi G, Christensen R, Bang D, Bodaghi B, Celik AF, Fortune F, Gaudric J, Gul A, Kötter I, Leccese P, Mahr A, Moots R, Ozguler Y, Richter J, Saadoun D, Salvarani C, Scuderi F, Sfikakis PP, Siva A, Stanford M, Tugal-Tutkun I, West R, Yurdakul S, Olivieri I, Yazici H. 2018 update of the EULAR recommendations for the management of Behçet's syndrome. Ann Rheum Dis. 2018 Jun;77(6):808-818. doi: 10.1136/annrheumdis-2018-213225. Epub 2018 Apr 6. — View Citation

Imrie FR, Dick AD. Biologics in the treatment of uveitis. Curr Opin Ophthalmol. 2007 Nov;18(6):481-6. Review. — View Citation

Pasadhika S, Rosenbaum JT. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis. Biologics. 2014 Feb 15;8:67-81. doi: 10.2147/BTT.S41477. eCollection 2014. Review. — View Citation

Rubsamen PE, Gass JD. Vogt-Koyanagi-Harada syndrome. Clinical course, therapy, and long-term visual outcome. Arch Ophthalmol. 1991 May;109(5):682-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	non-resolution of inflammation, or failure of complete clinical resolution of the primary lesion in cases of retinitis or choroiditis.	Prospective	at 6 month
Primary	Recurrence of inflammation described as a two-step increase in inflammation as defined by the SUN working group criteria for anterior and intermediate uveitis	prospective	at 6 month
Secondary	non-resolution of inflammation, or failure of complete clinical resolution of the primary lesion in cases of retinitis or choroiditis.	prospective	at 12 month
Secondary	Recurrence of inflammation described as a two-step increase in inflammation as defined by the SUN working group criteria for anterior and intermediate uveitis	prospective	at 12 month