Ciclosporin A Improves Severe Dry Eye Disease in Sjögren’s Syndrome Patients, Phase 3 Data Shows

Treatment with ciclosporin A — an anti-inflammatory medication — significantly improved the signs and symptoms of patients with moderate-to-severe dry eye disease (DED), including those with Sjögren’s syndrome, an analysis of two Phase 3 studies shows.

The study, “Efficacy and safety of 0.1% ciclosporin A cationic emulsion in dry eye disease: a pooled analysis of two double-masked, randomised, vehicle-controlled phase III clinical studies,” was published in the British Journal of Opthamology.

Dry eye disease affects 5 percent to 50 percent of the population worldwide. Patients experience a range of symptoms, including eye pain, eye irritation, difficulties performing basic activities, and visual problems such as blurry vision. Without treatment, the disease can progress and increase in severity. In some cases, it can lead to permanent eye damage.

Current treatment involves the use of artificial tears to lubricate and hydrate the eye surface. However, this provides only symptom relief and does not treat the main underlying issue in chronic DED — inflammation of the eye surface.

Ciclosporin A (CsA) is an anti-inflammatory medication that has been found to have substantial benefits in treating moderate-to-severe DED.

In 2015, CsA was produced in a new formulation — cationic emulsion (CE) — which contains 0.1 percent CsA, and was approved by the European Medicines Agency for the treatment of severe keratitis (inflammation of the cornea) in adults with DED.

Two European Phase 3 studies, SICCANOVE (2007-000029-23) and SANSIKA (2011-000160-97), conducted in patients with either moderate-to-severe or severe DED, found that CsA CE was well-tolerated and effective.

In this study, researchers conducted further analysis on pooled data from both studies to better determine the treatment effect of CsA CE, compared with the vehicle, which refers to only cationic emulsion without CsA, in multiple subgroups of patients, including patients with Sjögren’s syndrome.

For both studies, patients received either 0.1 percent CsA CE or vehicle once daily for six months. Effectiveness was determined using a combined assessment called corneal fluorescein staining — Ocular Surface Disease Index.

Results showed that patients treated with CsA CE were 1.66 times more likely to respond than patients treated with vehicle. Additionally, among patients with severe DED, those treated with CsA CE were 1.80 times more likely than vehicle-treated patients to respond.

Patients with Sjögren’s syndrome with severe DED were 3.37 times more likely to respond when treated with CsA CE than with vehicle. This finding is interesting because Sjögren’s syndrome is an autoimmune disease that causes dry eye, making it generally more severe and difficult to treat.

Researchers also measured levels of human leucocyte antigen-DR (HLA-DR) in the eye, which is a marker of eye surface inflammation. Treatment with CsA CE significantly reduced levels of median HLA-DR expression compared with vehicle at six months.

“The combined efficacy and safety data from this pooled analysis suggest that CsA CE … has a favourable safety and tolerability profile and is efficacious in improving both signs and symptoms of DED in patients with moderate-to-severe DED …, including patients with [Sjögren’s syndrome] with severe DED,” the researchers concluded.