Clinical efficacy of olopatadine vs epinastine ophthalmic solution in the conjunctival allergen challenge model

BACKGROUND: Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol) and epinastine hydrochloride 0.05% ophthalmic solution (Elestat) are two topical antiallergic agents. Olopatadine is indicated for the treatment of the signs and symptoms of allergic conjunctivitis that include itching, redness, tearing, lid swelling, and chemosis. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis. OBJECTIVE: This study compared the clinical efficacy of olopatadine and epinastine in the prevention of itching and conjunctival redness in the conjunctival allergen challenge (CAC) model. RESEARCH DESIGN AND METHODS: This was a prospective, randomized, double-masked, contralaterally-controlled, single center allergen challenge study. Ninety-six subjects with a history of allergic conjunctivitis were screened, and the 66 who responded to conjunctival allergen challenge at visits 1 and 2 were randomized into 1 of 3 treatment groups at visit 3 to receive one drop of study medication in each eye: (1) olopatadine in one eye and epinastine in the fellow eye, (2) olopatadine in one eye and placebo in the fellow eye, and (3) epinastine in one eye and placebo in the fellow eye. Five minutes after study drop instillation, subjects were bilaterally challenged with the allergen concentration that had elicited a positive conjunctival allergic response at Visits 1 and 2. Subjective itching assessments were given at 3 min, 5 min, and 7 min post challenge. Objective redness and chemosis assessments were made at 10 min, 15 min, and 20 min post challenge. Paired sample two-tailed t-tests were performed on the mean scores at each time point to assess statistical significance in the differences between treatments. MAIN OUTCOME MEASURES; RESULTS: Fifty-three subjects were randomized into the olopatadine/epinastine treatment group, the primary analysis group. Olopatadine treated eyes exhibited significantly lower mean itching and conjunctival redness scores than the contralateral epinastine treated eyes, -0.19 (p = 0.003) and -0.52 (p < 0.001), respectively. Olopatadine treated eyes also exhibited significantly less chemosis -0.24 (p < 0.001), ciliary redness -0.55 (p < 0.001), and episcleral redness -0.58 (p < 0.001) than epinastine treated eyes. CONCLUSION: Olopatadine is significantly more effective than epinastine in controlling itching, redness and chemosis associated with allergic conjunctivitis in the CAC model.     

Comparative efficacy of olopatadine 0.1% ophthalmic solution versus levocabastine 0.05% ophthalmic suspension using the conjunctival allergen challenge model

SUMMARY

Objective: To compare the efficacy of olopatadine and levocabastine in reducing ocular allergic itching and vascular hyperemia (redness) induced by conjunctival allergen challenge.

Research design and methods: The study was a randomized, double-masked, contralateral study using the conjunctival allergen challenge (CAC) model. At Visit 1, subjects with a positive allergen skin test and a history of allergic conjunctivitis were administered increasing concentrations of allergen until at least a moderate grade 2 ocular itching and conjunctival redness response was obtained in both eyes. Allergic signs were graded on standardized 0–4 scales. Subjects who reacted positively were re-challenged at Visit 2 with the pre-determined concentration of allergen. Subjects who again responded with at least a grade 2 bilateral ocular itching and conjunctival redness score at Visit 2 were eligible for drug evaluation. At Visit 3, subjects received olopatadine in one eye and levocabastine in the contralateral eye according to a computer-generated randomization scheme generated prior to commencement of the study. Ocular discomfort was then graded in both eyes. Subjects were bilaterally challenged with the predetermined concentration of allergen 27?min after topical drug administration, such that the first post-challenge assessment was made 30?min post-drug instillation. Allergic signs and symptoms were evaluated at 3?min, 10?min, and 20?min post-challenge and safety and efficacy analyses were performed.

Results: Sixty-eight subjects received study drug and were included in the safety and efficacy analyses. Ocular itching scores for olopatadine were significantly lower than levocabastine at 3?min and 10?min post-challenge (?p < 0.001). Ocular redness scores for olopatadine were significantly lower than levocabastine at all time points post-challenge (?p < 0.0001). Of all subjects, 4.41% reported ocular discomfort in the olopatadine eye and 26.5% in the levocabastine treated eye.

Conclusion: Olopatadine treated eyes had significantly less itching and redness than levocabastine treated eyes after conjunctival allergen challenge. Olopatadine was also associated with less discomfort upon instillation than levocabastine.     

Efficacy and comfort of olopatadine 0.2% versus epinastine 0.05% ophthalmic solution for treating itching and redness induced by conjunctival allergen challenge

ABSTRACT

Background: Olopatadine 0.2% (Pataday, Alcon Laboratories Inc., Fort Worth, Texas, USA) and epinastine 0.05% (Elestat, Inspire Pharmaceuticals, Inc., Durham, NC, USA) are topical ocular anti-allergic agents. Both are H₁ antihistamine/mast cell stabilizers indicated for the treatment of ocular itching associated with allergic conjunctivitis.

Objective: To compare the efficacy and comfort of olopatadine 0.2% with epinastine 0.05%, in the prevention of ocular itching associated with allergic conjunctivitis following conjunctival allergen challenge (CAC).

Research design and methods: This was a 7 week, four visit, double-masked, randomized, placebo-controlled CAC study. Visit 1 screened subjects for positive ocular allergic responses and Visit 2 confirmed those responses. At Visit 3, 92 subjects were randomized into one of four treatment groups to receive one drop of study medication in each eye: (1) olopatadine 0.2%/placebo, (2) epinastine 0.05%/placebo, (3) olopatadine 0.2%/epinastine 0.05%, (4) placebo/placebo. Subjects were challenged 12?h after drop instillation to evaluate duration of action. At Visit 4, subjects were challenged 5?min after drop instillation to evaluate onset of action. Drop comfort was assessed at Visit 4.

Main outcome measures; results: This article focuses on the results of the onset-of-action challenge (Visit 4). At Visit 4, ocular itching was assessed at 3, 5, and 7?min and redness was assessed at 7, 15, and 20?min post-challenge. Drop comfort was assessed upon instillation, at 30?s, and at 1, 2, and 5?min post-instillation. Olopatadine 0.2%-treated eyes exhibited significantly lower mean ocular itching scores versus epinastine 0.05%-treated eyes at 5 (?p = 0.024) and 7?min (?p = 0.003) post-challenge. Olopatadine 0.2%-treated eyes exhibited significantly lower mean redness scores versus epinastine 0.05%-treated eyes at all time points post-challenge (ciliary: p ≤ 0.013, conjunctival: p ≤ 0.015, episcleral: p ≤ 0.006). Olopatadine 0.2% was rated as significantly more comfortable than epinastine 0.05% at 1?min post-drop instillation (?p = 0.003). All adverse events were non-serious and unrelated to study medication. Although the CAC model reproduces allergic responses that are not environmentally-induced, patients experience varying severities of responses as are seen in real-world situations.

Conclusion: Olopatadine 0.2% was superior to epinastine 0.05% in preventing ocular itching and redness at onset when induced by the CAC model.     

Comparative efficacy of olopatadine 0.1% ophthalmic solution versus levocabastine 0.05% ophthalmic suspension using the conjunctival allergen challenge model

OBJECTIVE: To compare the efficacy of olopatadine and levocabastine in reducing ocular allergic itching and vascular hyperemia (redness) induced by conjunctival allergen challenge. RESEARCH DESIGN AND METHODS: The study was a randomized, double-masked, contralateral study using the conjunctival allergen challenge (CAC) model. At Visit 1, subjects with a positive allergen skin test and a history of allergic conjunctivitis were administered increasing concentrations of allergen until at least a moderate grade 2 ocular itching and conjunctival redness response was obtained in both eyes. Allergic signs were graded on standardized 0-4 scales. Subjects who reacted positively were re-challenged at Visit 2 with the pre-determined concentration of allergen. Subjects who again responded with at least a grade 2 bilateral ocular itching and conjunctival redness score at Visit 2 were eligible for drug evaluation. At Visit 3, subjects received olopatadine in one eye and levocabastine in the contralateral eye according to a computer-generated randomization scheme generated prior to commencement of the study. Ocular discomfort was then graded in both eyes. Subjects were bilaterally challenged with the predetermined concentration of allergen 27 min after topical drug administration, such that the first post-challenge assessment was made 30 min post-drug instillation. Allergic signs and symptoms were evaluated at 3 min, 10 min, and 20 min postchallenge and safety and efficacy analyses were performed. RESULTS: Sixty-eight subjects received study drug and were included in the safety and efficacy analyses. Ocular itching scores for olopatadine were significantly lower than levocabastine at 3 min and 10 min post-challenge (p < 0.001). Ocular redness scores for olopatadine were significantly lower than levocabastine at all time points post-challenge (p < 0.0001). Of all subjects, 4.41% reported ocular discomfort in the olopatadine eye and 26.5% in the levocabastine treated eye. CONCLUSION: Olopatadine treated eyes had significantly less itching and redness than levocabastine treated eyes after conjunctival allergen challenge. Olopatadine was also associated with less discomfort upon instillation than levocabastine.     

A review of olopatadine for the treatment of ocular allergy

Ocular allergy affects > 20% of the general population and many therapeutic preparations are available to individuals experiencing the most common forms--seasonal and perennial allergic conjunctivitis. 0.1% Olopatadine topical ophthalmic solution is currently approved for the treatment of allergic signs and symptoms in patients > or = 3 years of age. Olopatadine is available in Europe as Opatanol) and in > 30 other countries as Patanol. It inhibits mast cell degranulation and antagonises histamine receptors to manage the itching, redness, chemosis, tearing and lid swelling of the ocular allergic reaction, and its mast cell stabilising ability has been demonstrated both in vitro (using human conjunctival mast cells) and in vivo (human clinical experience). This article reviews both the laboratory and clinical information available on olopatadine, prefaced by a discussion of the current understanding of the ocular allergic reaction and followed by the future implications for this compound. Both laboratory and clinical studies have established the efficacy, safety and comfort of olopatadine in several study design models and comparisons to other antiallergy medications. The application of olopatadine, specifically in the management of lid swelling, an allergic sign recalcitrant to therapy and nasal allergic symptoms has also been established. In the future, a new formulation containing 0.2% olopatadine exhibits a duration of action up to 24 h, supporting once-daily dosing.     

Evaluation of the effects of olopatadine ophthalmic solution, 0.2% on the ocular surface of patients with allergic conjunctivitis and dry eye*

ABSTRACT

Purpose: Olopatadine hydrochloride 0.2% (Pataday^?, Alcon, Fort Worth, USA) is a topical ocular anti-allergic agent that has shown high rates of efficacy in treating ocular itching, the primary symptom of allergic conjunctivitis, and allows for once-daily dosing. Since some patients suffer from signs or symptoms of dry eye in addition to ocular allergy, this study was designed to evaluate the safety of olopatadine 0.2% in a population of patients with both allergic conjunctivitis and dry eye.

Methods: This was a single-center, 3-visit, double-masked, randomized study. Fifty-two patients diagnosed with ocular allergy and mild-to-moderate dry eye were evaluated. After a run-in period, patients were randomized to receive either olopatadine hydrochloride 0.2% or a tear saline, and self-dosed once-daily for 1 week. Outcome measures included tear film break-up time, corneal and conjunctival staining, tear volume and flow as measured by fluorophotometry, Schirmer's test, injection, and symptom evaluations.

Results: No significant differences between the treatment groups were observed (?p > 0.05). No serious adverse events occurred during the trial. Variability in the presentation of dry eye can hinder the observation of treatment effects. Although the study design facilitated the comparison of olopatadine 0.2% against an agent that was certain to not exacerbate dry eye, future comparison of olopatadine 0.2% against other agents in its drug class would provide useful information about relative drug tolerabilities.

Conclusion: As there were no significant changes in the signs and symptoms of dry eye, olopatadine hydrochloride 0.2% is safe to use in ocular allergy patients with mild-to-moderate dry eye.     

A review of olopatadine for the treatment of ocular allergy

Ocular allergy affects > 20% of the general population and many therapeutic preparations are available to individuals experiencing the most common forms – seasonal and perennial allergic conjunctivitis. 0.1% Olopatadine topical ophthalmic solution is currently approved for the treatment of allergic signs and symptoms in patients ≥ 3 years of age. Olopatadine is available in Europe as Opatanol^® and in > 30 other countries as Patanol^®. It inhibits mast cell degranulation and antagonises histamine receptors to manage the itching, redness, chemosis, tearing and lid swelling of the ocular allergic reaction, and its mast cell stabilising ability has been demonstrated both in vitro (using human conjunctival mast cells) and in vivo (human clinical experience). This article reviews both the laboratory and clinical information available on olopatadine, prefaced by a discussion of the current understanding of the ocular allergic reaction and followed by the future implications for this compound. Both laboratory and clinical studies have established the efficacy, safety and comfort of olopatadine in several study design models and comparisons to other antiallergy medications. The application of olopatadine, specifically in the management of lid swelling, an allergic sign recalcitrant to therapy and nasal allergic symptoms has also been established. In the future, a new formulation containing 0.2% olopatadine exhibits a duration of action up to 24 h, supporting once-daily dosing.     

Topical azelastine in perennial allergic conjunctivitis

SUMMARY

Objective: Azelastine is a selective H1-receptor antagonist that inhibits histamine release and interferes with activation of several other mediators of allergic inflammation. Together with demonstrated efficacy in seasonal allergic conjunctivitis, azelastine indicated a therapeutic potential for perennial allergic conjunctivitis (PAC).

The present study aimed to evaluate azelastine eye drops in patients with PAC compared to placebo.

Research design and methods: A multinational trial in 22 centres randomised 139 patients to twice-daily treatment for 6 weeks with masked 0.05% azelastine eye drops, matching masked placebo, or open-label levocabastine. Randomisation required a sum itching and conjunctival redness score of at least 3 (0-6 scale) after 1 week of placebo. The change in sum score was evaluated during treatment.

Results: Azelastine significantly improved itching and conjunctival redness compared to placebo (p?<?0.001) with global tolerability that was not substantially different from placebo. On day 7, the mean symptoms sum score improved with azelastine by 1.9?±?1.1 and with levocabastine by 1.5?±?1.2 compared to placebo (0.6?±?1.1) from baseline values of 3.7-3.8. The sum scores continued to improve up to day 42. Daily patient logs confirmed the clinically assessed scores. Most frequent adverse events following azelastine were bitter taste and application site reaction.

Conclusions: Topical azelastine progressively improved itching and conjunctival redness in PAC patients compared to placebo and was at least as effective as levocabastine. Rapid relief is consistent with H1-receptor antagonist action, while continued improvement up to 6 weeks may be consistent with mechanisms involving other mediators of allergic inflammation.     

Preliminary observations on the use of propionyl-L-carnitine in combination with sildenafil in patients with erectile dysfunction and diabetes

ABSTRACT

Background: Histamine receptor activation and degranulation of mast cells are the mechanisms by which the ocular itching, hyperemia, chemosis, eyelid swelling, and tearing of seasonal allergic conjunctivitis are induced. Some of the topical solutions available as anti-allergy therapies are intended to interfere with these mechanisms, and the body of research regarding the capabilities of these therapeutic molecules continues to expand.

Objective: To review the currently available literature regarding one topical ophthalmic anti-allergy agent, olopatadine (Patanol), and its anti-histaminic and mast cell stabilizing actions, both in pre-clinical and clinical settings.

Design and methods: Relevant research of laboratory, animal model, and clinical trial studies performed using olopatadine was reviewed. MEDLINE literature searches were conducted and supplemented by additional reports which furthered relevant discussion or were necessary to verify the information resulting from original searches.

Results: Olopatadine demonstrates unique properties both pre-clinically and clinically which differentiate it from other therapeutic molecules in its class of dual action mast cell stabilizer/anti-histamine. Its non-perturbation of cell membranes, human conjunctival mast cell stabilization in vivo and in vitro, and superior efficacy as compared to other topical anti-allergic medications including mast cell stabilizers, anti-histamines, and dual action agents, all contribute to olopatadine's profile.

Conclusions: Peer-reviewed literature suggests that olopatadine is clinically superior to the other anti-allergic molecules because of its strong anti-histaminic qualities and its unique ocular mast cell stabilizing properties.     

Efficacy and comfort of olopatadine versus ketotifen ophthalmic solutions: a double-masked,environmental study of patient preference

SUMMARY

Background: Ocular allergies cause itching, redness, chemosis, tearing, and swelling of the eyelids in sensitized individuals. The options available for treatment of ocular allergy include olopatadine 0.1% (Opatanol; Patanol [US]*) and ketotifen 0.025% (Zaditen; Zaditor [US]?). Patient preference for an eye drop can often be a primary factor in determining the level of compliance and satisfaction with any given therapy.

Objective: This study sought patient perspective on eye drop efficacy in controlling signs and symptoms of allergic conjunctivitis and eye drop comfort. Also evaluated were the factors considered by patients when making decisions of preference.

Methods: One hundred patients with previous history and current symptoms of seasonal or perennial allergic conjunctivitis were enrolled at two centers (Athens, Greece, N = 50; Padova, Italy, N = 50) for this two visit, double-masked study. Qualified patients received two masked bottles of medication (one olopatadine, one ketotifen) and were asked to use both medications as needed over the course of four weeks, but not to exceed usage of two drops of medication per eye per day. At the second visit, patients answered five questions comparing the two masked medications in terms of preference, drop comfort, and efficacy in treatment of signs and symptoms. Patients also defined the factors upon which they based these decisions.

Results: A significantly greater percentage of patients (81%) selected olopatadine when asked which medication they preferred; which they found more comfortable; which they found more efficacious in reducing symptoms of allergy; and which they would select if visiting the doctor's office (P < 0.0001). Seventy-six percent (76%) of patients considered both efficacy and comfort when making their preference decisions (P < 0.0001). No adverse events were volunteered or elicited.

Conclusion: In this study, patients preferred to use the anti-allergy eye drop olopatadine over ketotifen after using both drops and evaluating relative efficacy and comfort during the course of four weeks. A significantly greater percentage of the patients preferred to use olopatadine during the study period, found it more efficacious and comfortable, and would select olopatadine if visiting their doctor's office during allergy season.     

Olopatadine: a drug for allergic conjunctivitis targeting the mast cell

Importance of the field: Ocular allergic diseases are characterized by specific activation of conjunctival mast cells with subsequent release of preformed and newly formed mediators. Mast cells are thus the first therapeutic target of ocular anti-allergic treatments.

Areas covered in this review: In this review, a Medline literature search was conducted on conjunctival mast cells, their role in ocular allergy and mast cell stabilization by ocular anti-allergic compounds.

What the reader will gain: Olopatadine hydrochloride, a mast cell stabilizer and histamine receptor antagonist, has been shown to inhibit mast cell activation in an in vitro model of human mast cell culture, reducing histamine and TNF-α release and upregulating proinflammatory mediators in conjunctival epithelial cells. In the in vivo conjunctival allergen challenge (CAC) model in allergic subjects, combined with objective evaluations of tear mediators and cytology, olopatadine reduced histamine tear levels and all aspects of allergic inflammation, confirming the positive clinical effects observed in active allergic patients.

Take home message: Mast cells play a central role in the pathogenesis of ocular allergy. The CAC model is ideal for assessing the mast cell stabilizing effects of anti-allergic compounds. This review of clinical studies demonstrates the superiority of olopatadine compared with other topical allergic drugs.     

Efficacy and comfort of olopatadine versus ketotifen ophthalmic solutions: a double-masked, environmental study of patient preference

BACKGROUND: Ocular allergies cause itching, redness, chemosis, tearing, and swelling of the eyelids in sensitized individuals. The options available for treatment of ocular allergy include olopatadine 0.1% (Opatanol; Patanol [US]) and ketotifen 0.025% (Zaditen; Zaditor [US]). Patient preference for an eye drop can often be a primary factor in determining the level of compliance and satisfaction with any given therapy. OBJECTIVE: This study sought patient perspective on eye drop efficacy in controlling signs and symptoms of allergic conjunctivitis and eye drop comfort. Also evaluated were the factors considered by patients when making decisions of preference. METHODS: One hundred patients with previous history and current symptoms of seasonal or perennial allergic conjunctivitis were enrolled at two centers (Athens, Greece, N = 50; Padova, Italy, N = 50) for this two visit, double-masked study. Qualified patients received two masked bottles of medication (one olopatadine, one ketotifen) and were asked to use both medications as needed over the course of four weeks, but not to exceed usage of two drops of medication per eye per day. At the second visit, patients answered five questions comparing the two masked medications in terms of preference, drop comfort, and efficacy in treatment of signs and symptoms. Patients also defined the factors upon which they based these decisions. RESULTS: A significantly greater percentage of patients (81%) selected olopatadine when asked which medication they preferred; which they found more comfortable; which they found more efficacious in reducing symptoms of allergy; and which they would select if visiting the doctor's office (P < 0.0001). Seventy-six percent (76%) of patients considered both efficacy and comfort when making their preference decisions (P < 0.0001). No adverse events were volunteered or elicited. CONCLUSION: In this study, patients preferred to use the anti-allergy eye drop olopatadine over ketotifen after using both drops and evaluating relative efficacy and comfort during the course of four weeks. A significantly greater percentage of the patients preferred to use olopatadine during the study period, found it more efficacious and comfortable, and would select olopatadine if visiting their doctor's office during allergy season.     

Comparison of the efficacy and tolerability of topically administered azelastine,sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis

SUMMARY

Objective and setting: Azelastine (AZE) in a novel, eye drop, formulation, was compared with topically applied sodium cromoglycate (SCG) and placebo (PLA) in the treatment of seasonal allergic conjunctivitis or rhino-conjunctivitis in a multicentre, parallel group study.

Research design: 144 subjects ranging in age from 16 to 65 years participated. All had at least a 2-year history of seasonal allergic conjunctivitis and were symptomatic at the time of inclusion.

Medications were administered topically either twice daily (AZE/PLA) or four times daily (SCG) over a 2-week treatment period.

Method and outcome measures: Azelastine and placebo were compared double-blind; the comparison versus SCG was carried out in an open manner. Itching, redness, flow of tears, eyelid swelling, foreign-body sensation, photophobia, soreness and discharge were scored on a 4-point severity scale.

Results: Results for the decrease of main conjunctivitis symptoms (itching, tearing and conjunctival redness) showed a marked effect for both active treatments on day 3 with a sustained improvement on days 7 and 14. A clear response to treatment (an improvement of sum scores for day 3 of >3 points compared to baseline) occurred in 85.4% of azelastine-treated patients, 83.0% of sodium cromoglycate patients and 56.3% of placebo patients. Response rates for both active treatments were statistically superior to those for placebo (azelastine p?=?0.005; sodium cromoglycate p?=?0.007). Global assessment of efficacy was at least 'satisfactory' for 90.0% of azelastine patients, 81.3% of sodium cromoglycate patients and 66.3% of placebo-treated patients. The most frequent adverse effects were transient application site reactions which tended to disappear with increasing duration of treatment, and, less frequently, taste perversion.

Conclusion: The results of this study indicate that the therapeutic use of azelastine eye drops in patients with seasonal allergic conjunctivitis or rhino-conjunctivitis can be recommended.     

Azelastine eye drops in the treatment of perennial allergic conjunctivitis

Azelastine (CAS 58581-89-8) is a selective H1-receptor antagonist that inhibits histamine release and interferes with activation of other mediators of allergic inflammation. The present double-blind study aimed to evaluate azelastine eye drops (Allergodil) in patients with perennial allergic conjunctivitis compared to placebo. A total of 116 patients with an ocular symptoms score for itching and conjunctival redness > or = 3 (0-6 scale) were randomized to twice-daily 0.05% azelastine eye drops treatment (n = 58) or placebo. Patients maintained daily logs and were clinically evaluated after 7, 21 and 42 days of treatment. Azelastine significantly improved itching and conjunctival redness versus placebo (p < 0.001). Tolerability was rated good or better by 97% of patients with only bitter taste and application site reaction notable adverse experiences. On Day 7, ocular symptoms score improved by 1.5 +/- 0.9 (versus 0.5 +/- 0.8 placebo) with score improvement > or = 2 in 55% with azelastine (versus 14% placebo). Itching and redness further improved at Day 42 (score improvement > or = 2 in 95% with azelastine versus 33% placebo) and completely resolved for 47% azelastine patients (versus 10% placebo). Daily patient logs confirmed the clinically assessed scores. Topical azelastine progressively improved itching and conjunctival redness in patients with moderate to severe perennial allergic conjunctivitis. Continued improvement with prolonged use is consistent with mechanisms other than H1-receptor blockade, such as possible down regulation of adhesion molecule receptors.     

Topical azelastine in perennial allergic conjunctivitis

OBJECTIVE: Azelastine is a selective H(1)-receptor antagonist that inhibits histamine release and interferes with activation of several other mediators of allergic inflammation. Together with demonstrated efficacy in seasonal allergic conjunctivitis, azelastine indicated a therapeutic potential for perennial allergic conjunctivitis (PAC). The present study aimed to evaluate azelastine eye drops in patients with PAC compared to placebo. Research design and methods: A multinational trial in 22 centres randomised 139 patients to twice-daily treatment for 6 weeks with masked 0.05% azelastine eye drops, matching masked placebo, or open-label levocabastine. Randomisation required a sum itching and conjunctival redness score of at least 3 (0-6 scale) after 1 week of placebo. The change in sum score was evaluated during treatment. RESULTS: Azelastine significantly improved itching and conjunctival redness compared to placebo (p < 0.001) with global tolerability that was not substantially different from placebo. On day 7, the mean symptoms sum score improved with azelastine by 1.9 +/- 1.1 and with levocabastine by 1.5 +/- 1.2 compared to placebo (0.6 +/- 1.1) from baseline values of 3.7-3.8. The sum scores continued to improve up to day 42. Daily patient logs confirmed the clinically assessed scores. Most frequent adverse events following azelastine were bitter taste and application site reaction. CONCLUSIONS: Topical azelastine progressively improved itching and conjunctival redness in PAC patients compared to placebo and was at least as effective as levocabastine. Rapid relief is consistent with H(1)-receptor antagonist action, while continued improvement up to 6 weeks may be consistent with mechanisms involving other mediators of allergic inflammation.     

The effect of montelukast on rhinitis symptoms in patients with asthma and seasonal allergic rhinitis

SUMMARY

Objective: The objective of this study was to evaluate montelukast 10?mg daily as treatment for allergic rhinitis in patients with symptomatic allergic rhinitis and active asthma during the allergy season.

Methods: This was a multicenter study of 831 patients (ages 15?years–85?years) with seasonal allergen sensitivity, active symptoms of seasonal allergic rhinitis, and active asthma. Following a single-blind, placebo run-in period of 3?days–5?days, patients were randomized to oral montelukast 10?mg (n = 415) or placebo (n = 416) daily during the 2-week, double-blind, active-treatment period.

Main outcome measures: The primary endpoint was Daily Rhinitis Symptoms score, average of Daytime Nasal Symptoms and Nighttime Symptoms, as self-rated by patients on a 0–3 scale on daily diaries.

Results: Montelukast reduced the Daily Rhinitis Symptoms score: difference between montelukast and placebo in mean change from baseline was –0.12 [95% CI –0.18, –0.06; p ≤ 0.001]. Similar improvements were seen in Daytime Nasal Symptoms (–0.14 [–0.21, –0.07; p ≤ 0.001]) and Nighttime Symptoms (–0.10 [–0.16,–0.04; p ≤ 0.001]). Improvements (p < 0.05) were seen in Daytime Eye Symptoms and in the secondary endpoints of Global Evaluations of AR by Patient and by Physician, and Rhinoconjunctivitis Quality of Life. In exploratory analyses, improvement in rhinitis symptoms was numerically (though not statistically) larger in patients with greater levels of asthma at study start. Montelukast provided benefit in the Global Evaluations of Asthma by Patient and by Physician: mean differences were –0.24 [–0.41, –0.06; p = 0.008] and –0.17 [–0.33,–0.01; p = 0.037]. Similarly, as-needed β-agonist use (puffs/day) was reduced with montelukast (?p ≤ 0.005).

Conclusion: Montelukast provides significant relief from symptoms of seasonal allergic rhinitis, while also conferring a benefit for asthma, in patients with both allergic rhinitis and asthma.     

Properties of olopatadine hydrochloride, a new antiallergic/antihistaminic drug

Olopatadine hydrochloride (CAS 140462-76-6, KW-4679, AL-4943A; hereinafter referred to as olopatadine) is a novel antiallergic drug that is a selective histamine H1 receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibits the tachykininergic contractions in guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Oral administration of olopatadine at doses of 0.03 mg/kg or higher reduces the symptoms of experimental allergic cutaneous responses and rhinoconjunctivitis in sensitized animals. Preclinical and clinical evaluations have demonstrated that olopatadine is a safe drug. After oral administration to healthy volunteers, olopatadine was rapidly and extensively absorbed. Unlike most other antiallergic drugs which are eliminated via hepatic metabolism, olopatadine is mainly excreted into urine. Olopatadine did not affect cytochrome P450 activities in human liver microsomes and consequently drug-drug metabolic interactions are unlikely. In double-masked clinical trials, olopatadine was shown to be effective at alleviating symptoms of allergic diseases. The drug (Allelock) was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, cutaneous pruritis, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000. An ophthalmic solution of olopatadine is also useful for the treatment of allergic conjunctivitis: this formulation (Patanol) was approved in the USA and the European Union for the treatment of seasonal and perennial allergic conjunctivitis in 1996 and 2002, respectively.     

Ocular allergic disease

Ocular allergy is a common condition that usually affects the conjunctiva of the eye and is therefore often referred to as allergic conjunctivitis. The severity of the disease can range from mild itching and redness, as seen in seasonal allergic conjunctivitis, to the more serious vision threatening forms of ocular allergy which affect the cornea, such as atopic keratoconjunctivitis. The pathogenesis of allergic conjunctivitis involves a complex mechanism which centers around IgE-mediated mast cell degranulation and release of multiple preformed and newly formed inflammatory mediators. The diagnosis of allergic conjunctivitis is usually a clinical one which can be made based on a thorough history and careful examination. Treatment of ocular allergy should begin with conservative measures including allergen avoidance, environmental control, ocular irrigation and cold compresses. Pharmacotherapy of allergic conjunctivitis consists of several classes of drugs. Antihistamines are widely used to treat mild conditions such as seasonal and perennial conjunctivitis and potent new agents such as levocabastine and emedastine are now available. Mast cell stabilizers such as sodium cromoglycate are both safe and effective and are commonly used in ocular allergy. More effective mast cell stabilizers such as nedocromil, lodoxamide and olopatadine are now being used. Nonsteroidal antiinflammatory drugs have demonstrated only limited efficacy and, as such, are not widely used. Topical steroids are very effective in treating signs and symptoms but are reserved for only refractory cases due to their serious side effects. Loteprednol and rimexelone are newer corticosteroids which reportedly have less of an effect on intraocular pressure. Cyclosporine has recently been shown to be highly effective in cases of vernal keratoconjunctivitis and atopic keratoconjunctivitis while producing no adverse effects.     

Pharmacokinetic evaluation of olopatadine for the treatment of allergic rhinitis and conjunctivitis

INTRODUCTION: Olopatadine hydrochloride is an antihistamine and mast cell stabilizer available in three forms, including oral, intranasal and ocular preparations. Most of the practical applications focus on the use of olopatadine for the treatment of allergic rhinitis and conjunctivitis via intranasal and ocular routes. AREAS COVERED: This article was formed from a comprehensive literature search with information taken from meta-analyses, systematic reviews, treatment guidelines and clinical studies on children and adults. Articles that have been selected evaluate the use of intranasal and ocular antihistamines and their role in allergic rhinitis and conjunctivitis. EXPERT OPINION: Olopatadine is significantly more effective than placebos in alleviating the symptoms of allergic rhinitis and conjunctivitis. Olopatadine is a viable alternative and addition to the mainstay therapy of these conditions with intranasal steroids and oral antihistamines. The compliance of the patients would be improved if a once-per-day formulation of olopatadine was developed for intranasal application. The future treatments of allergic rhinitis will probably involve a combination of intranasal antihistamine and steroid because clinical trials have demonstrated an improved efficacy without a significant increase in adverse effects.     

奥洛他定滴眼液联合普拉洛芬滴眼液治疗过敏性结膜炎的临床疗效

目的研究奥洛他定滴眼液联合普拉洛芬滴眼液治疗过敏性结膜炎的临床疗效。方法将136例过敏性结膜炎患者随机分为奥洛他定联合普拉洛芬组82例及单纯奥洛他定组54例,进行治疗,观察治疗前后患者症状与体征的变化情况,评价临床疗效。结果治疗结束后,两组患者的症状和体征均得到显著的改善,奥洛他定联合普拉洛芬组与单纯奥洛他定组的总有效率分别为97.6%及88.9%,两组比较,差异有显著性(P<0.05)。两组患者治疗期间未观察到明显的不良反应。结论奥洛他定滴眼液联合普拉洛芬滴眼液治疗过敏性结膜炎具有较好的临床疗效和安全性,值得临床推广应用。