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Pooled results from two prospective, multicenter, double-masked, placebo-controlled studies show a multi-modal anti-allergy product, bepotastine besilate ophthalmic solution 1.5%, provides rapid and long-lasting clinically significant improvement in allergen-induced ocular itching.
The phase III studies were performed using the conjunctival allergen challenge model (CAC). They enrolled 157 patients who demonstrated both a positive skin test to the challenge allergen 24 months prior to enrollment and grade 2 or worse ocular itching after allergen challenge at each of two screening visits based on a 5-point rating scale (0 = none, 4 = severe).
In the study period, patients were randomly assigned to receive a single drop of bepotastine besilate 1.5% or placebo into both eyes at one visit and were treated with the alternate study agent at a subsequent visit. CAC was performed at 15 minutes, 8 hours, and 16 hours post-instillation of the study agent (bepotastine or placebo), and participants were asked to grade the severity of ocular itching.
Analyses comparing proportions of eyes that achieved a 1.0-unit or greater improvement from baseline itching score showed statistically significant differences favoring bepotastine over placebo at all three testing intervals (p < 0.05).
Upon exposure to allergen 15 minutes post-dosing, 95% of bepotastine-treated eyes achieved a 1.0-unit or greater improvement from baseline itching score, and 68.3% of bepotastine-treated eyes with itching rated severe (3 or greater) had no itch within 3 minutes of the challenge. When challenged 8 hours and 16 hours post-dosing with bepotastine, itching severity scores group were improved by at least 1.0 unit from the baseline value in 89% and 76% of eyes, respectively.
However, following placebo treatment across all three test periods, fewer than half of the eyes (40% to 47%) had a 1.0-unit or greater improvement from baseline itching score, and only 3.1% of eyes with itching rated severe were itch-free at 3 minutes after the challenge (15 minutes after placebo instillation).
"By eliminating many of the variables encountered in real-world, environmental studies, the standardized CAC model for testing anti-allergy agents enables determination of a product's efficacy for relieving itching . . . in terms of defining [both] its onset of action and duration," Dr. O'Brien said. "Considering the data for both the proportion of eyes achieving a 1.0-unit reduction in itch severity compared with baseline, an improvement [that] is considered to be clinically relevant, and the proportion that were itch-free at 15 minutes, the results for bepotastine are impressive."
Maintaining ocular itch relief
Bepotastine besilate 1.5% is indicated for twice-daily administration in the treatment of seasonal allergic conjunctivitis (SAC). However, the results of this study indicate that the majority of patients may expect to maintain meaningful relief of their ocular itching for at least up to 16 hours post-dosing, he said.
"These data suggest that patients who miss a dose of bepotastine may still be able to maintain symptomatic control for another several hours, at least, and they also indicate an opportunity for flexibility in the dosing regimen depending on the patient's severity of symptoms," he said.
Dr. O'Brien suggested that patients who are in the midst of an acute flare of SAC should be instructed to use their bepotastine drops twice a day, but as their symptoms are controlled, they may find adequate benefit with just once-daily dosing. Considering the potent and rapid onset of action of bepotastine, eventually treatment may even be transitioned to an as-needed schedule.
However, Dr. O'Brien also observed that although there are many studies establishing the value of a more convenient dosing schedule for increasing medication adherence in asymptomatic conditions, reducing dosing frequency from twice to once daily may be less important for patients using an anti-allergy product for symptomatic SAC than it would be for those with other diseases.
"Maximizing the simplicity of the dosing regimen to once a day is particularly useful for optimizing compliance among patients with ocular hypertension or early glaucoma who may omit doses because their disease is asymptomatic," Dr. O'Brien said.
"However, dosing convenience may be less tied to medication use by patients with SAC, particularly if they are experiencing an acute flare, because the potential to achieve rapid and sustained relief from bothersome symptoms will motivate them to use their drops," he added. "Nevertheless, there are advantages for patients if they can decrease the number of daily doses without compromising comfort from allergy control in terms of reducing cost and exposure to preservatives."
The efficacy demonstrated by bepotastine besilate in the CAC study may be understood based on the pharmacologic profile of this multimodal anti-allergy product. Bepotastine besilate is a highly potent and selective histamine-1 receptor antagonist that also offers mast cell stabilization properties and activity against late-phase reactants of the allergic cascade.
"Although the effects of bepotastine on the late-phase reactants are less well-studied and less well-understood, it may be that the activity of bepotastine for mitigating the effects of those mediators accounts for its long-lasting benefit for relieving ocular allergic symptoms," Dr. O'Brien concluded.
Terrence P. O'Brien, MD
Dr. O'Brien is an ad hoc nonsalaried consultant to several companies that manufacture anti-allergy compounds, including Alcon Laboratories, Allergan, Bausch + Lomb, Inspire Pharmaceuticals, and ISTA Pharmaceuticals.