Lifitegrast yields treatment benefit across symptom endpoints

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A phase III clinical trial of lifitegrast 5% ophthalmic solution for treatment of dry eye showed treatment benefit across all symptom endpoints.

Dr. Tauber

By Cheryl Guttman Krader; Reviewed by Joseph Tauber, MD

Kansas City, MO-Results from a phase III clinical trial of lifitegrast 5% ophthalmic solution (Shire) for the treatment of dry eye show the novel anti-inflammatory agent had a significant benefit compared with placebo for reducing patient-reported symptoms, but not corneal staining.

Thus, per protocol for the OPUS-2 trial, the investigational compound failed to meet its co-primary endpoint.

Nevertheless, the efficacy of lifitegrast for improving the co-primary symptom endpoint is noteworthy because of its rapid onset, consistency with other symptom outcome measures, and when considering the data in the context of prior studies of treatments for dry eye, said Joseph Tauber, MD, Tauber Eye Center, Kansas City, MO.

“To the best of my knowledge, this is the first time that a pharmacologic treatment for dry eye achieved a statistically significant improvement in patient symptoms,” Dr. Tauber said. “Against that background and the fact that the improvement was so robust, occurring across every primary, secondary, and tertiary symptom outcome measure, the benefit of lifitegrast for relieving symptoms is pretty impressive.”

He observed that because previously reported results from OPUS-1-the other phase III trial-showed lifitegrast was associated with a significant improvement in corneal staining but not in dry eye symptoms, the outcomes in OPUS-2 were somewhat unexpected.

However, Dr. Tauber said the data serve to underscore the well-known fact that there is very poor correlation between the objective measures of dry eye and how patients feel.

“Furthermore, as we dig into the pathophysiology of the disease, it is not clear that signs and symptoms will improve simultaneously,” he continued.

“This potential disconnect raises a question about what the FDA should consider with respect to FDA approval of any investigational agent for dry eye,” Dr. Tauber said. “However, from my viewpoint as a practitioner, the fact that a medication for dry eye is able to make patients feel better is very important because of its potential to improve well-being and medication adherence.”

About OPUS-2

OPUS-2 included 718 adults who were using artificial tears and had moderately symptomatic dry eye disease, an abnormal Schirmer tear test, moderate corneal staining, and mild hyperemia. After a 14-day placebo run-in, they were randomly assigned 1:1 to twice-daily use of lifitegrast 5% or placebo. Artificial tears were not allowed during the 84-day, double-masked, treatment period.

The study population had an average age of about 60 years, were predominantly female (~75%), and mainly white (~85%). About 93% of patients completed the study.

Patients returned for evaluation 14, 42, and 84 days after starting treatment. Already by the first follow-up visit, lifitegrast was associated with a statistically significant benefit for greater reduction in patient-reported eye dryness (p = 0.003).

Further improvement occurred in both the lifitegrast and placebo groups over time, but the magnitude of change was greater in the lifitegrast patients, and the difference between groups at days 42 and 84 was highly statistically significant (p < 0.001).

“We don’t know if patients would experience even greater relief with ongoing lifitegrast treatment, but the trend in the data suggests it is a possibility,” Dr. Tauber said.

Inferior corneal staining scores also improved in both groups over time, but there was no difference between lifitegrast and placebo at any visit.

Secondary symptom endpoints evaluated in the study included ratings of ocular discomfort and eye discomfort, and there was a treatment benefit of lifitegrast for both measures at days 42 and 84. Changes from baseline in Ocular Surface Disease Index scores and visual analogue scale ratings of itching, foreign body sensation, photophobia, and pain also favored lifitegrast compared with placebo. As for the primary staining endpoint, secondary signs of total fluorescein staining of the cornea and nasal lissamine staining showed no differences between treatment groups at any follow-up.

Lifitegrast was well–tolerated and was not associated with any serious ocular adverse events. The most common adverse events in patients using lifitegrast were dysgeusia (16.2%), instillation site irritation (7.8%), and irritation site reaction (7%). Five patients (1.4%) discontinued lifitegrast due to instillation site irritation and there were four withdrawals in the lifitegrast group attributed to eye irritation. No patients in the placebo group withdrew from the study because of ocular adverse events.

Novel mechanism of action

Lifitegrast is an ICAM-1 decoy, interfering with the homing of activated T-cells to the ocular surface.

“By preventing pathogenic cells from reaching the ocular surface, lifitegrast reduces inflammation and dry eye-related symptoms,” Dr. Tauber said. “The fact that it has a unique mechanism of action, different than any other treatment for dry eye, also supports the idea that it would be an important therapeutic addition.”

Joseph Tauber, MD

E: jt@tauberye.com

Dr. Tauber has received fees from Shire as clinical trial investigator and consultant.