Boston–Alcaftadine ophthalmic solution 0.25% (Lastacaft, Allergan) was superior to olopatadine hydrochloride ophthalmic solution 0.2% (Pataday, Alcon) in reducing the itching related to grass and tree pollens in a multicenter, randomized study in subjects with allergic conjunctivitis.
Alcaftadine was significantly more effective than olopatadine in reducing the itching caused by grass pollen at 16 hours after dosing, and for tree pollen at 24 hours after dosing.
The investigators were interested in identifying efficacy subgroups for the two drugs, based on animal studies suggesting that alcaftadine 0.25% stabilizes epithelial tight junctions better than olopatadine 0.1%.
One of the investigators, Joseph B. Ciolino, MD, a specialist in corneal and external diseases, Massachusetts Eye and Ear Infirmary, Harvard University, referenced the 2011 study by Ono and Lane, which concluded that alcaftadine reduced conjunctival eosinophil recruitment and had a protective effect on epithelial tight junction protein expression. Given the Ono study findings, Dr. Ciolino hypothesized that alcaftadine may decrease allergen load to antibody receptor sites in resident and mast cells, which may explain why alcaftadine might have had greater efficacy than olopatadine 0.2% for some allergen sensitivities.
The double-masked, randomized, placebo- and active-controlled trial was conducted at 5 centers, enrolling 111 subjects: 95 had allergen sensitivities to grasses and 16 to trees. After undergoing two conjunctival allergen challenges (CAC), subjects were randomized to receive 1 drop of alcaftadine or olopatadine.
Sixteen hours after dosing, they were challenged with the allergen dose determined on the second CAC visit. Subjects assessed their itching at 3, 5, and 7 minutes after the challenge and lid swelling and tearing at 7, 15, and 20 minutes after challenge.
An investigator assessed redness and chemosis at 7, 15, and 20 minutes. In another study, subjects were challenged and these assessments were repeated 24 hours after dosing with the drugs.
The earliest time point, 3 minutes post-CAC, is the most important, Dr. Ciolino said, since at this time point, histamine is at its highest concentration in the tissue, and patients are likely to immediately rub their eyes, which then triggers additional histamine release.
In grass-allergic subjects 16 hours after the dose of anti-allergy medication, results at 3 minutes post-CAC showed that alcaftadine (mean itching score of 0.52) was superior to olopatadine (mean itching score of 0.95 [p=0.011]).
“At the early time point, the change from baseline itching was -2.2 for alcaftadine versus -1.5 for olopatadine (p=0.003), corresponding to an 80% decrease in baseline itching in subjects treated with alcaftadine, compared with a 60% decrease in baseline thing in subjects treated with olopatadine (p=0.005),” Dr. Ciolino said.
Alcaftadine was also superior in the category of subjects with minimal itching (less than 1 on a 4-point scale); in 95 grass-allergic subjects, 38 (79%) subjects who had received alcaftadine had a low score versus 25 (54%) of those who received olopatadine.
In the study of tree-allergic subjects 24 hours after dosing (n=16), results 3 minutes post-CAC showed that the mean difference between alcaftadine (mean itching score of 0.50) and olopatadine (mean itching score of 1.38) was -0.88 (p=0.135).
The change from baseline was -2.4 for alcaftadine versus -1.1 for olopatadine (p=0.048), which corresponded to a percentage change from baseline of -83.3% for alcaftadine versus -41.4% for olopatadine (p=0.045). Five patients treated with alcaftadine (83%) versus 2 (33%) who had received olopatadine reported minimal itching of less than 1 on the 0-4 itching scale (p=0.242).