DRY EYE TREATMENT

Long-term treatment of dry eye disease with the novel investigative agent lifitegrast (Shire) appears safe, although it does appear to produce a relatively high rate of adverse events, suggest the results of a one-year prospective, randomised, placebo-controlled study conducted in the USA. Eric Donnenfeld MD, New York University, presented the results of the SONATA study during the World Cornea Congress VII in San Diego, USA. 

The SONATA trial enrolled 331 patients, all with Schirmer’s test ranging from 1.0 to 10mm without anaesthesia, and corneal staining scores above two. The patients were randomised two-to-one to receive either lifitegrast 5.0 per cent ophthalmic solution b.i.d. or placebo for one year.

Some 53 per cent of patients on active treatment had treatment-emergent adverse events at some point during the study, versus 34 per cent in the placebo group. The most common complaints were irritation at the instillation site (burning etc), seen in 15 per cent, and transient blurred vision, seen in 13 per cent.

“Drilling down, looking at the more significant trend of treatment-emergent adverse events leading to discontinuation, 18 patients (8.2 per cent) discontinued lifitegrast. The most common reasons were instillation site reaction or transient blurred vision, with increased lacrimation and reduced visual acuity. But only two patients, 0.9 per cent, discontinued treatment because of burning, actually less than in the control group,” reported Dr Donnenfeld.

As for non-ocular adverse events leading to discontinuation, 1.8 per cent stopped treatment because of dysgeusia, a distortion of the sense of taste. There was no indication of systemic toxicity, due to local or systemic immunosuppression.

The SONATA trial, a US FDA registration study, also had secondary exploratory objectives. Among these, the study found no significant changes in visual acuity, slit lamp microscopy, dilated fundoscopy, or intraocular pressure (IOP) associated with active treatment. There was also no worsening of corneal fluorescein staining related to the eye drop, and no evidence of accumulation of lifitigrast in plasma, over time.

“The percentage of treatment-associated adverse events was higher in the lifitigrast treatment group than in the placebo group, but most notably, there were no serious adverse ocular events. Discontinuation due to adverse events was infrequent. Lifitegrast ophthalmic solution 5.0 per cent b.i.d. appears to be safe and well tolerated with no unexpected adverse events. These results support the safety profile seen in the earlier OPUS 1 and OPUS 2 trials,” Dr Donnenfeld told the session.

Lifitegrast is a first-in-class small-molecule integrin inhibitor. It binds to the integrin LFA-1 (lymphocyte function-associated antigen-1), a cell surface protein found on leukocytes, and blocks the interaction of LFA-1 with its cognate ligand ICAM-1 (intercellular adhesion molecule-1). Blocking ICAM-1 is believed to inhibit T-cell activation at the ocular surface.

Eric Donnenfeld: ericdonnenfeld@gmail.com