Evaluation of the Efficacy and Safety of Tacrolimus Drops in Children With Vernal Keratoconjunctivitis (KERAVER)

Evaluation of the Efficacy and Safety of Tacrolimus 0.1% Ophthalmic Solution in Children With Vernal Keratoconjunctivitis Resistant to Ciclosporin 2% Ophthalmic Solution: a Single-center Retrospective Cohort Study

Non-interventional single-center cohort study (Rothschild Foundation Hospital) of patients aged 0 to 18 years followed up in ophthalmology for KCV, treated with tacrolimus 0.1% eye drops previously treated with ciclosporin 2% with treatment failure.

1. Prospective collection of quality of life from the parents and/or, if possible, the children via the QUICK questionnaire and 6 additional questions
2. Retrospective collection of clinical data (secondary endpoints) from the patients' medical records, aiming to compare the period before the start of treatment and the period under treatment with TALYMUS

The objective of this study is to evaluate the response to TALYMUS® treatment in patients with Vernal keratoconjunctivitis who have failed ciclosporin 2% therapy, whether due to lack of efficacy, compliance difficulties or poor tolerance.

Study Overview

• Status: Completed
• Conditions: Vernal Keratoconjunctivitis
• Intervention / Treatment: Procedure: QUICK questionnaire and 6 additional questions; Other: Retrospective collection of clinical data from the patients' medical records

Detailed Description

Vernal keratoconjunctivitis (VKC) is a chronic inflammatory eye disease affecting children and adolescents. It is a disease of allergic origin which, if left untreated, can have a significant impact on quality of life, daily activities and learning. In some cases, sequelae of the disease or complications from the treatments used can lead to permanent vision impairment.

Symptoms of VKC include intense itching, tearing, mucous secretions, burning, foreign body sensation and severe photophobia. Clinical signs include conjunctival and corneal involvement -which may leave scarring opacities-and in the most severe stage, limbal insufficiency with definitive corneal conjunctivalization.

There is no consensus on the therapeutic strategy to adopt. Treatment is based on a combination of antihistamines and mast cell stabilizers, and in case of failure on corticosteroids. Cortico-resistant or cortico-dependent forms require treatment with local or general immunosuppressants, because of the long-term ocular complications of corticosteroids. These local immunosuppressants, belonging to the class of calcineurin inhibitors, have been used in ophthalmology for many years in hospital preparations of ciclosporin eye drops. More recently, commercial forms have appeared on the market: RESTASIS® (0.05% cyclosporine eye drops), IKERVIS® and VERKAZIA® (0.1% cyclosporine eye drops), CICLOGRAFT® (2% cyclosporine eye drops) and TALYMUS® (0.1% tacrolimus eye drops).

Although TALYMUS® has French marketing authorization for VKC, its place in the therapeutic strategy and its positioning in relation to the various cyclosporine eye drops is not clearly established. Series have reported similar efficacy of TALYMUS® and 0.05% and 2% cyclosporine in patients with KCV, at a lower dosage than those usually required for cyclosporine eye drops (2 drops per day for TALYMUS® versus 3 to 4 drops per day for cyclosporine). Given the difficulties of compliance in children, particularly in a school environment and in the context of a chronic pathology, the possibility of a less frequent administration represents a significant advantage. The simplicity of use and efficacy of TALYMUS® , as well as its safety profile, which is comparable to that of cyclosporine eye drops, have led some authors to recommend it as a first-line eye drop on a par with cyclosporine.

In addition, in numerous publications and in our experience, there are cases of failure of treatment with cyclosporine eye drops, which have even led some authors to recommend for many years only hospital preparations of cyclosporine at concentrations greater than or equal to 1%. It is therefore to be expected that cases of resistance to VERKAZIA® will appear.

One study reported the efficacy of a 0.1% tacrolimus hospital preparation in patients who had failed 1% cyclosporine therapy. However, the efficacy of TALYMUS® treatment in patients who have failed ciclosporin 2% therapy has not been reported to date.

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• France
  • Paris, France, 75019
    • Hôpital Fondation A. de Rothschuld

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with vernal keratoconjunctivitis, treated (or having been treated) with tacrolimus 0.1% ophthalmic solution previously treated with ciclosporin 2% ophthalmic solution with treatment failure.

Description

Inclusion Criteria:

• Patients followed in ophthalmology for vernal keratoconjunctivitis .
• Treated (or having been treated) with tacrolimus 0.1% ophthalmic solution previously treated with ciclosporin 2% ophthalmic solution with treatment failure.

Exclusion Criteria:

• Parental opposition

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients aged 0 to 18 years followed for Vernal keratoconjunctivitis; Treated (or having been treated) with tacrolimus 0.1% ophthalmic solution previously treated with ciclosporin 2% ophthalmic solution with treatment failure.	Procedure: QUICK questionnaire and 6 additional questions; QUICK questionnaire and 6 additional questions; Other: Retrospective collection of clinical data from the patients' medical records; Retrospective collection of clinical data from the patients' medical records

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life with TALYMUS® ophthalmic solution versus ciclosporin 2% ophthalmic solution	Score distribution of the QUICK questionnaire with TALYMUS® ophthalmic solution versus ciclosporin 2% ophthalmic solution in children with vernal keratoconjunctivitis treated with TALYMUS® ophthalmic solution due to ciclosporin 2% failure	Day 1

Collaborators and Investigators

• Sponsor: Fondation Ophtalmologique Adolphe de Rothschild
• Investigators: Principal Investigator: Rebecca Rebecca, Hôpital Fondation A. de Rothschild; Study Chair: Gilles MARTIN, Hôpital Fondation A. de Rothschild

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2021
• Primary Completion (Actual): October 25, 2021
• Study Completion (Actual): November 10, 2021

Study Registration Dates

• First Submitted: September 30, 2021
• First Submitted That Met QC Criteria: September 30, 2021
• First Posted (Actual): October 13, 2021

Study Record Updates

• Last Update Posted (Actual): November 17, 2021
• Last Update Submitted That Met QC Criteria: November 16, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Tacrolimus; Vernal keratoconjunctivitis
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Eye Diseases; Hypersensitivity; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Conjunctivitis, Allergic; Keratoconjunctivitis
• Other Study ID Numbers: RGR_2021_21

Drug and device information, study documents

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