Efficacy of Ketotifen Fumarate 0.025% Ophthalmic Solution Compared With Placebo in the Conjunctival Allergen Challenge Model

Abstract

Background: Ketotifen fumarate blocks histamine 1 (H 1 ) receptors, stabilizes mast cells, and acts as an eosinophil inhibitor (decreases chemotaxis and activation of eosinophils).Objective: To assess the efficacy of ketotifen 0.025% ophthalmic solution in the prevention of symptoms of allergic conjunctivitis, using the conjunctival allergen challenge model. Methods:This was a single-center, double-masked, randomized, placebo-controlled, contralateral-eye comparison, allergen challenge trial conducted in the United States. Subjects were randomized to receive ketotifen 0.025% in one eye and placebo in the other. At visits 1 and 2, allergen challenges were performed to determine the allergen concentration eliciting a qualifying reaction for each subject. At the 3 subsequent visits, subjects received 1 drop of ketotifen 0.025% ophthalmic solution in one eye and vehicle solution as placebo in the other eye 15 minutes (visit 3), 6 hours (visit 4), and 8 hours (visit 5) be-fore allergen challenge. The primary efficacy measure was the subject's rating of itching at 3, 7, and 10 minutes after challenge. CLINICAL SCIENCES

Ketotifen directly modifies the fibrotic response of human skin fibroblasts

“…Pirfenidone targets TGFβ1-induced signaling factors leading to attenuated collagen and αSMA protein 32 , while nintedanib inhibits receptor tyrosine kinases of crucial growth factor receptors in fibrotic conditions 33 . The mast cell stabilizer ketotifen is currently used to treat allergic conjunctivitis and other allergic disorders 34 , 35 . In experimental models of skin wound repair and knee arthrofibrosis, ketotifen decreased fibrosis 23 , 24 .…”

Clinical Efficacy of a Ginkgo biloba Extract in the Topical Treatment of Allergic Conjunctivitis

“…The ophthalmic therapies available for preventing and treating these allergic diseases are somewhat limited (6). Most of the drugs available are membrane stabilizers intended to inhibit the degranulation process of the mast cells and the release of inflammation mediators (16); antihistaminic drugs, that more or less selectively inhibit H 1 receptors, are considered to exert excellent clinical effects, but cause a wide range of side effects (17,18). The use of topical nonsteroidal anti-inflammatory drugs, which inhibit the release of inflammation substances such as prostaglandins, demonstrate efficacy in reducing inflammation without any side effects (19).…”

Immunomodulators for conjunctivitis

“…Using IgE-sensitized human conjunctival mast cell and later challenged with anti-IgE, ketotifen at concentration of 10 À10 to 10 À4 mol/l was shown to block the release of histamine and tryptase by 90% [37]. Ketotifen was also shown to be effective in preventing symptoms of allergic conjunctivitis using conjunctival allergen challenge model [40], as well as in pollen allergen challenge chamber [41]. Moreover, production of TNF-a and IL-5 was inhibited by ketotifen in this system.…”