Evaluation of 0.05% CsA and 0.1% FK506 Eye Drops in Ocular GVHD Treatment

Evaluation of Efficacy, Safety and Tolerability of 0.05% Cyclosporine and 0.1% Tacrolimus Eye Drops in the Treatment of Chronic Ocular Graft-versus-host Disease

It is planned to explore the efficacy and safety of local 0.05% cyclosporine eye drops in the treatment of chronic graft-versus-host eye disease. Through the comparative study with 0.1% tacrolimus eye drops, to clarify the short-term and long-term efficacy of 0.05% CSA in these patients, and to explore the benefits of long-term maintenance of local cyclosporine to patients.

Study Overview

• Status: Completed
• Conditions: Graft Versus Host Disease in Eye
• Intervention / Treatment: Drug: Cyclosporine; Drug: tacrolimus

Detailed Description

Chronic graft-versus-host disease (GVHD) is a common and serious complication after allogeneic hematopoietic stem cell transplantation. Its clinical presentation is similar to that of an autoimmune disease and can affect many organs, including the skin, liver, gastrointestinal tract, lungs and eyes. Ocular GVHD occurs in 30-60% of patients undergoing hematopoietic stem cell transplantation and 60-90% of patients with other systemic GVHD. Chronic ocular GVHD usually occurs 9-24 months after hematopoietic stem cell transplantation and mainly affects the cornea, conjunctiva, lacrimal gland, eyelid and meibomian gland, and leads to inflammation and fibrosis of these tissues. The characteristic manifestations of chronic GVHD include dry keratoconjunctivitis, cicatric conjunctivitis, punctate keratopathy, corneal ulcer and perforation. Severe dry eye is the most common manifestation of ocular GVHD. Patients have burning sensation, foreign body sensation, photophobia, dry eye, itching and other symptoms. This is associated with reduced tear secretion due to damage to the lacrimal gland as well as with goblet cell loss and tear film instability due to meibomian gland dysfunction. Chronic eye GVHD has the potential to cause severe visual impairment and significantly reduce the patient's quality of life. The principle of topical treatment of ocular GVHD is to lubricate the ocular surface, reduce ocular surface inflammation, prevent tear evaporation, and promote epithelial repair. Specific local treatment options include glucocorticoids, immunosuppressants, growth factors and artificial tears. Local glucocorticoids are the first-line treatment at the present stage, but the side effects of hormone therapy are relatively large. Long-term use can lead to damaged epithelial formation, thinning of the cornea, increased intraocular pressure, cataract, infectious keratitis, etc. Therefore, it is necessary to closely monitor the treatment period and minimize the use time. At present, the most commonly used topical immunosuppressants are tacrolimus (FK506) and cyclosporine (CsA). Both belong to calcineurin inhibitors, which can inhibit the activation of calcium-dependent T cells, thus exerting immunosuppressive effect. 0.05% CsA is an eye drop mainly used for the treatment of moderate and severe dry eye, with good therapeutic effect and tolerability [18-23], but slow onset of effect. In the treatment of patients with chronic ocular GVHD, previous studies have shown that cyclosporine eye drops can improve patients' dry eye symptoms, reduce corneal fluorescence staining, and increase tear film rupture time. However, the number of clinical studies on the treatment of chronic ocular GVHD with 0.05% CsA eye drops is limited, with a small number of patients enrolled and relatively short follow-up time. The immunosuppressive effect of tacrolimus is significantly higher than cyclosporine, which is 100 times higher than reported in literature. Therefore, tacrolimus is mainly used for the treatment of rejection after corneal transplantation and immune-related ocular surface diseases. What is the efficacy and tolerability of such a powerful immunosuppressant in treating GVHD? There are few literature reports, but long-term ocular application can reduce local immunity and increase the risk of local infection. At the same time, tacrolimus is very irritating, and some patients cannot tolerate it and choose to stop using the drug. At present, there is still a lack of clinical evidence to compare the efficacy of cyclosporine and tacrolimus eye drops in patients with chronic ocular GVHD. Therefore, by comparing the effectiveness, safety and tolerance of 0.05% CsA eye drops and 0.1% tacrolimus eye drops in the treatment of chronic eye graft-versus host eye disease, this study aims to explore a reasonable treatment plan for chronic eye GVHD and provide theoretical basis for clinical application.

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed as chronic ocular GVHD
• Did not receive eye local immunosuppressive therapy
• Non pregnant patients

Exclusion Criteria:

• Have a history of eye surgery in the past six months
• Suffering from other eye diseases (autoimmune diseases, glaucoma, serious infection, retinopathy, allergy, cataract, eye trauma, etc.)
• Hormones or immunosuppressants were used before enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cyclosporine group; The chronic ocular GVHD patients in cyclosporine group received local 0.05% cyclosporine 4 times/day for 3 months, and then changed to 0.05% cyclosporine for 2 times/day for 3 months	Drug: Cyclosporine; The chronic ocular GVHD patients in cyclosporine group received local 0.05% cyclosporine 4 times/day for 3 months, and then changed to 0.05% cyclosporine for 2 times/day for 3 months; Other Names: CsA
Experimental: tacrolimus group; The chronic ocular GVHD patients in tacrolimus group received local 0.05% tacrolimus 2 times/day for 3 months, and then changed to 0.05% cyclosporine for 2 times/day for 3 months	Drug: tacrolimus; The chronic ocular GVHD patients in tacrolimus group received local 0.05% tacrolimus 2 times/day for 3 months, and then changed to 0.05% cyclosporine for 2 times/day for 3 months; Other Names: FK506

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
visual acuity	visual acuity	Within 4 hours of initial enrollment
visual acuity	visual acuity	At the first month of enrollment
visual acuity	visual acuity	At the third month of enrollment
visual acuity	visual acuity	At the sixth month of enrollment
Intraocular pressure	Intraocular pressure	Within 4 hours of initial enrollment
Intraocular pressure	Intraocular pressure	At the first month of enrollment
Intraocular pressure	Intraocular pressure	At the third month of enrollment
Intraocular pressure	Intraocular pressure	At the sixth month of enrollment
Ocular Surface Disease Index	Ocular Surface Disease Index	Within 4 hours of initial enrollment
Ocular Surface Disease Index	Ocular Surface Disease Index	At the first month of enrollment
Ocular Surface Disease Index	Ocular Surface Disease Index	At the third month of enrollment
Ocular Surface Disease Index	Ocular Surface Disease Index	At the sixth month of enrollment
Corneal fluorescein staining	Corneal fluorescein staining	Within 4 hours of initial enrollment
Corneal fluorescein staining	Corneal fluorescein staining	At the first month of enrollment
Corneal fluorescein staining	Corneal fluorescein staining	At the third month of enrollment
Corneal fluorescein staining	Corneal fluorescein staining	At the sixth month of enrollment
Tear break-up time	Tear break-up time	Within 4 hours of initial enrollment
Tear break-up time	Tear break-up time	At the first month of enrollment
Tear break-up time	Tear break-up time	At the third month of enrollment
Tear break-up time	Tear break-up time	At the sixth month of enrollment

Collaborators and Investigators

• Sponsor: Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Actual): June 1, 2021
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: February 7, 2022
• First Submitted That Met QC Criteria: March 14, 2022
• First Posted (Actual): March 24, 2022

Study Record Updates

• Last Update Posted (Actual): March 24, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: dry eye; tacrolimus; cyclosporine; prospective study; ocular graft-versus-host disease
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Tacrolimus; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 99304

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