Ciclosporin A Cationic Emulsion (CsA CE; Ikervis, Santen) significantly improved signs and symptoms of dry eye disease in a randomised controlled trial.
The treatment also appeared safe, reported Dr Andrea Leonardi at the University of Padua and colleagues in the British Journal of Ophthalmology
Dry eye is a multifactorial disease of the ocular surface, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities all play a role.
Artificial tears have been the mainstay of treatment, but this approach provides only short-term symptomatic relief that does not address ocular surface inflammation.
Ciclosporin A, an anti-inflammatory agent, has shown significant benefits in moderate-to-severe cases of dry eye. But when applied topically in an oil-based formulation, it has low bioavailability and is poorly tolerated.
In 2015, the European Medicine Agency approved CsA CE for severe keratitis in adults with dry eye disease that had not improved with tear substitutes. CsA CE has a longer precorneal residence time and better bioavailability than previously available formulations, allowing for once-daily instillation.
Phase III data
To understand the size of the treatment effect, Dr Leonardi and colleagues pooled the results of two double-masked, randomised, vehicle-controlled Phase III studies: SICCANOVE in patients with moderate-to-severe disease and SNSIKA in patients with severe disease.
In both studies, adult Europeans were randomly assigned to receive either once-daily CsA CE 0.1% (1 mg/mL) or its vehicle for 6 months.
In SICCANOVE, patients had at least one symptom of ocular discomfort with a severity score of at least two on a four-point scale, tear breakup time of 8 seconds or less, a corneal fluorescein (CFS) staining score between two and four on the modified Oxford 0-5 scale, a Schrmer test without anaesthesia of at least 2 mm/5 minutes and less than 10 mm/5 minutes, and a corneal/conjunctival lissamine green staining score of at least four on the van Bijsterveld scale.
In SANSIKA, patients had CFS scores of four, a Schirmer test at least 2 mm/5 minutes and less than 10 mm/5 minutes, and Ocular Surface Disease Index score of at least 23.
The pooled analysis included 734 patients, 395 receiving CsA CE and 339 receiving the vehicle. Overall demographic and baseline disease characteristics were similar, with 84.7% women, 43.5% categorised as having severe disease and 36.6% diagnosed with Sjögren’s syndrome.
Overall, 21.6% of patients receiving CsA CE had an improvement of at least two grades from baseline in CFS and at least 30% in OSDI, compared with 13.1% of those receiving the vehicle, a statistically significant difference (P=0.015). The average CFS treatment difference between these two groups was –0.303 in favour of those receiving CsA CE.
In those with severe disease at baseline, 29.5% of those receiving CsA CE had a CFS-OSDI response, compared with 18.3% of those receiving the vehicle, also a significant difference (P=0.038).
The differences between the treatment group and the vehicle group among patients with Sjögren’s syndrome were not statistically significant, except among those with both Sjögren’s and severe dry eye disease. Among these patients, 23.4% of those receiving CsA CE had a CFS-OSDI response, compared with 9.4% of those receiving only the vehicle (P=0.030).
In most patient subgroups, the researchers found a significant CFS treatment effect in favour of CsA CE. This was most notable among older patients; the difference between those receiving CsA CE and those receiving only the vehicle among those aged 65 to 74 years of age was –0.568 and among those over 75 years of age it was –0.569. Among female patients it was –0.349. Treatment with CsA CE also produced improvements in CFS score regardless of Sjögren’s status.
The investigators noted adverse events to the treatments in 33.9% of the patients receiving CsA CE and 20.3% of those receiving the vehicle. They were mostly ocular, including instillation site pain, eye irration and instillation site irritation.
One patient in the CsA CE group had severe corneal epithelial erosion that resolved without sequelae, while a patient in the vehicle group had decreased best-corrected distance visual acuity. There were no serious systemic effects reported.
The researchers concluded that CsA CE was safe and effective in the treatment of patients with moderate to severe dry eye disease, especially those with severe keratitis, and including those with Sjögren’s.