Nasal Effects/Adjuntive or Combined Therapy 

BACKGROUND: Ketotifen fumarate 0.025% ophthalmic solution is an antiallergic treatment currently available in the United States. It is indicated for the temporary prevention of ocular itching due to allergic conjunctivitis.

OBJECTIVE: The purpose of this study was to determine the relative efficacy of ketotifen when applied topically to the eye, compared with placebo, in the treatment of nasal signs and symptoms of allergic rhinoconjunctivitis as induced by the conjunctival allergen challenge (CAC) model.

METHODS: This was a randomized, double-blind, parallel-group, single-center clinical study using the CAC model. Patients aged ≥ 18 years, able to follow the study instructions, willing to avoid disallowed medications, and having a history of rhinoconjunctivitis and a positive skin test were eligible. At visit 1, the dose of allergen necessary to achieve a qualifying reaction was determined using bilateral ocular instillation of allergen to eligible patients. At visit 2, the allergen dose determined at visit 1 was confirmed, and all patients attaining a qualifying nasal reaction continued in the study. At visit 3, each patient was randomized to receive 1 drop of ketotifen bilaterally in the eyes or 1 drop of placebo bilaterally. Fifteen minutes after instillation of the study medication, bilateral CAC was performed. Patients rated nasal symptoms (sneezing, rhinorrhea and postnasal drip, nasal pruritus, palatal pruritus and nasal congestion) on standardized scales at 10, 20, and 30 minutes after CAC.

RESULTS: Thirty-two patients (16 men, 16 women; mean age 45 years [range, 28-70 years]) were randomized to treatment and completed the study. Nineteen patients received ketotifen and 13 received placebo. Nasal symptom scores in ketotifen-treated patients were statistically and clinically significantly fewer than those treated with placebo at all time points (mean baseline corrected total nasal score: 10 minutes, p = 0.010; 20 minutes, p = 0.025; 30 minutes, p = 0.006).

CONCLUSIONS: In this study, topical ketotifen fumarate 0.025% ophthalmic solution, when dosed ocularly, offered protection against the nasal signs and symptoms of acute allergic rhinoconjunctival reaction as induced by the CAC model.

Efficacy and safety of ketotifen eye drops as adjunctive therapy to mometasone nasal spray in subjects with seasonal allergic rhinoconjunctivitis.Horak F; Stübner P; Zieglmayer R; McWhirter CL; Gekkieva M: ENT Clinic, University of Vienna, Vienna, Austria; Novartis Ophthalmics Inc, Duluth, GA, USA; Novartis Ophthalmics AG, Bülach, Switzerland. Clin Drug Invest 2003; 23: 597-604

OBJECTIVE: To compare the efficacy and safety of ketotifen 0.025% ophthalmic solution (one drop/eye) with placebo as adjunctive therapy to mometasone nasal spray (50 µg/spray, two puffs/nostril) in subjects with seasonal allergic rhinoconjunctivitis (SARC).

METHODS: Single-centre, randomised, double-masked, two-treatment, two-period crossover study. 8-hour allergen challenge in the Vienna Challenge Chamber. Subjects were ≥18 years old, had a ≥ 2-year history of SARC, and were sufficiently responsive to allergen challenge. During each challenge, subjects received a single dose of mometasone + ketotifen or mometasone + placebo.

RESULTS: 47 subjects were randomised, and 44 completed both treatment sequences. Efficacy was based on mean area under the curve (AUC) values for symptom relief scores over time, with the primary variable being the AUC 4-6 hours postdose (AUC_4-6) for relief of ocular itching. Between-treatment differences were assessed using analysis of variance. While improvement in ocular itching (AUC_4-6 ) was observed with both treatments, improvement was significantly (p = 0.014) better with mometasone + ketotifen versus mometasone + placebo, as was improvement based on AUC_0-6 (p = 0.009) and AUC_0-2 (p = 0.006). Similar trends (in favour of mometasone + ketotifen) were observed for improvements in ocular redness, running nose, sneezing and ocular/nasal composite scores (p ≤ 0.05). None of the safety findings (slit-lamp biomicroscopy, vital signs, adverse events) were clinically significant. One subject discontinued treatment due to mild pharyngitis.

CONCLUSIONS: Ketotifen eye drops adjunctive to mometasone nasal spray provided greater relief of both ocular and nasal signs and symptoms than mometasone alone in subjects with SARC.

Comparison of ketotifen fumarate ophthalmic solution alone, desloratadine alone, and their combination for inhibition of the signs and symptoms of seasonal allergic rhinoconjunctivitis in the conjunctival allergen challenge model: a double-masked, placebo- and activecontrolled trial.

Crampton HJ: Ophthalmic Research Associates Inc, North Andover, MA, USA. Clin Ther 2003; 25: 1975-1987

BACKGROUND:Ketotifen fumarate is a topical antiallergic combination mast-cell stabilizer and antihistamine indicated for the temporary prevention of ocular itching due to allergic conjunctivitis. Desloratadine is a systemic antihistamine indicated for the treatment of seasonal and perennial allergic rhinitis.

OBJECTIVE: The purpose of this study was to compare the efficacy of ketotifen 0.025% ophthalmic solution instilled in the eye, desloratadine 5-mg tablets taken orally, and their combination for prevention of the signs and symptoms of allergic rhinoconjunctivitis, as induced by the conjunctival allergen challenge (CAC) model.

METHODS: This was a randomized, double-masked, placebo- and active-controlled, singlecenter clinical trial. At visit 1, the dose of allergen necessary to elicit a qualifying allergic reaction was determined for subjects meeting the entry criteria. At visit 2, the allergen dose determined at visit 1 was confirmed, and all subjects who had a qualifying ocular and nasal allergic reaction were randomized to 1 of 3 treatment groups: ketotifen ophthalmic solution and placebo tablet, desloratadine tablet and placebo eyedrop, or ketotifen and desloratadine. Subjects were instructed to instill 1 drop into each eye twice daily and take 1 tablet with water once daily at the same time as the morning eyedrop for ~4 weeks. At visit 3, subjects brought in their medication and were given 1 drop of the eyedrop bilaterally and 1 tablet with water. Bilateral CAC was performed 2 hours after administration of medication. Using standardized scales, subjects rated ocular itching at 3, 5, and 7 minutes after CAC; ocular tearing and eyelid swelling at 10, 15, and 20 minutes after CAC; and nasal signs and symptoms (sneezing, rhinorrhea and postnasal drip, pruritus, and nasal congestion) at 10, 20, 30, 40, and 50 minutes after CAC. The investigator graded ocular redness and chemosis at 10, 15, and 20 minutes after CAC. At all visits, subjects were offered an anti-allergy eyedrop to relieve any immediate ocular discomfort caused by CAC.

RESULTS: One hundred two subjects were screened - 82 (55 women, 27 men; mean age, 42.8 years [range, 21-70 years]) were randomized to treatment, and 80 completed the study. Subjects in the group that received ketotifen (n = 27) and the group that received ketotifen with desloratadine (n = 26) had significantly lower mean itching scores compared with those in the group that received desloratadine alone (n = 27) at all time points (p ≤0.05). Total ocular redness, calculated by summing the mean redness scores for each of the 3 vessel beds, was significantly lower in the ketotifen group than in the other treatment groups at most time points (p ≤0.05). All treatments attenuated nasal symptoms; no statistically significant differences were noted between treatment groups, with the exception of the 50-minute time point, at which combination treatment was significantly more effective than ketotifen alone (p ≤0.05). The proportion of subjects who requested relief drops after CAC was significantly lower in both the ketotifen alone and combination treatment groups compared with the desloratadine alone group (p = 0.004).

CONCLUSIONS: Ketotifen ophthalmic solution significantly decreased the signs and symptoms of ocular and nasal allergic rhinoconjunctivitis. The addition of ketotifen to the oral desloratadine regimen improved the overall antiallergic efficacy of both medications.