Recommendations for the pharmacologic management of allergic rhinitis.

Allergic rhinitis (AR) affects at least 60 million people in the United States each year, resulting in a major impact on patient quality of life, productivity, and direct and indirect costs. As new therapies, data, and literature emerge in the management of AR, there is a need to communicate and disseminate important information to health care professionals to advance the practice of medicine and lessen the disease burden from AR. Treatment recommendations for AR have not been updated since the 2012 Food and Drug Administration approval of nonaqueous intranasal aerosol agents using hydrofluoroalkane propellants and the first aqueous intranasal combination product. Here, we present an updated algorithm for the pharmacologic treatment of AR that includes these new treatment options. Treatment recommendations are categorized by disease severity (mild versus moderate/severe) and duration of symptoms (episodic versus nonepisodic, with episodic defined as <3 days/wk or for <3 weeks). Preferred treatments are suggested, as well as alternative options for consideration by clinicians in the context of individual patient needs. This recommendation article also outlines the importance of treatment monitoring, which can be conducted using the recently developed Rhinitis Control Assessment Test. Successful therapeutic outcomes depend on multiple factors, including use of the most effective pharmacologic agents as well as patient adherence to therapy. Therefore, it is imperative that rhinitis patients not only receive the most effective therapeutic options, but that they also understand and are able to adhere to the comprehensive treatment regimen. Successful treatment, with all of these considerations in mind, results in better disease outcomes, improved quality of life for patients, and greater economic productivity in the home and workplace.

Efficacy of once-daily olopatadine 0.2% ophthalmic solution compared to twice-daily olopatadine 0.1% ophthalmic solution for the treatment of ocular itching induced by conjunctival allergen challenge.

Olopatadine 0.1% (Patanol) and olopatadine 0.2% (Pataday) ophthalmic solutions are topical ocular anti-allergic agents with antihistaminic and mast cell stabilizing properties. The efficacy of two doses of olopatadine 0.1% was compared to one dose of olopatadine 0.2% in the prevention of ocular itching associated with allergic conjunctivitis over 24 hours. This double-masked conjunctival allergen challenge (CAC) study found no significant difference in the mean itching scores between two drops of olopatadine 0.1% and one drop of olopatadine 0.2%. Both showed significant activity at the 24-hour time point and were statistically superior to placebo. No adverse events occurred while on drug therapy.

Randomized, double-masked comparison of olopatadine ophthalmic solution, mometasone furoate monohydrate nasal spray, and fexofenadine hydrochloride tablets using the conjunctival and nasal allergen challenge models.

BACKGROUND: It is presumed that exposure to allergens in the environment occurs through both the eyes and the nose. Allergic rhinoconjunctivitis is typically treated with a nasal spray or systemic antihistamine, neither of which may provide adequate relief of the ocular component of the disease. OBJECTIVE: This study was designed to gain a better understanding of the physiologic interaction between the conjunctival and nasal mucosa and thus help establish a profile for the most effective ocular treatment in patients whose allergies have both an ocular and a nasal component. METHODS: This was a single-center, randomized, double-masked clinical study using the conjunctival allergen challenge (CAC) and nasal allergen challenge (NAC) models. It compared the clinical signs and symptoms induced by CAC and NAC, the effects of drugs administered by 3 different routes, and the movement of fluorescein after instillation into the eye and nose (Jones test), and assessed levels of of inflammatory mediators in tears and nasal secretions. At visit l, subjects previously identified as CAC responders underwent NAC to determine the dose of allergen necessary to elicit a sufficient positive reaction. At visit 2, which took place 1 week later, subjects with a positive reaction at visit 1 were randomized to group A (CAC) or group B (NAC), and underwent challenge to confirm the allergen dose necessary to produce a positive reaction. Subjects who qualified were randomized to receive 1 of 3 treatments: olopatadine 0.1% ophthalmic solution, placebo nasal spray, and placebo tablets; mometasone furoate monohydrate 50-microg nasal spray, placebo topical solution, and placebo tablets; or fexofenadine hydrochloride 180-mg tablets, placebo topical solution, and placebo nasal spray. All study medications were administered according to their approved labeling: drops were administered twice daily in the eyes, and the nasal sprays and tablets were administered once daily. At visit 3, which took place 1 week after visit 2, subjects received study medication and 15 minutes later underwent CAC or NAC as before. The primary efficacy variables were ocular itching, ocular redness, and overall nasal symptoms (sneezing, rhino rrhea/postnasal drip, nasal pruritus, palatal pruritus, and nasal congestion) rated on standard scales. Peak nasal inspiratory flow (PNIF) was measured at each visit, and the Jones test was performed at visits 1 and 3. At baseline and after challenge at visits 2 and 3, tear and nasal lavage samples were collected from a subset of randomly selected subjects for analysis of eosinophil cationic protein and tryptase. RESULTS: Seventy-three subjects (42 women, 31 men; mean age, 45.26 years [range, 21-73 years]) were screened, and all were randomized to treatment. Two subjects did not complete the study. CAC induced clinically significant (>1 unit difference) ocular and nasal signs and symptoms, whereas NAC induced clinically significant nasal signs and symptoms only. In group A, there was a greater reduction in ocular itching with olopatadine compared with mometasone and fexofenadine at 3 minutes (P = 0.003 and P = 0.008, respectively) and 5 minutes (P = 0.007 and P = 0.013) after challenge. Although the difference was not statistically significant, overall relief of conjunctival redness (average of 3 vessel beds) was greatest in the olopatadine group, followed by fexofenadine. In group B, prevention of total nasal symptoms was significantly greater with mometasone compared with fexofenadine at 20 minutes (P = 0.006) and 30 minutes (P = 0.014) after challenge. There were no statistically significant differences between treatment groups in nasal symptom scores at any time point after CAC. There were also no significant differences in PNIF between treatment groups. Fluorescein was present in nasal secretions within 5 minutes of being instilled into the eye; no fluorescein was detected in the eye after instillation into the nose. CONCLUSIONS: In this study, exposure of the nasal mucosa to allergen resulted in allergic rhinitis, and exposure of the ocular the ocular surface to allergen resulted in conjunctivitis with a secondary effect in the nose. These results suggest movement of allergens, their mediators, and antiallergy drugs from the ocular surfaces into the nasal cavity, with no meaningful movement from the nasal cavity to the ocular surface. In this controlled model, both the systemic agent and the nasal spray failed to control ocular symptoms. The topical ophthalmic solution provided the most effective management of allergic ocular signs and symptoms, and the nasal spray was most effective for nasal symptoms. Combined use of a nasal spray and topical ophthalmic solution may provide maximal relief in patients whose allergies have both ocular and nasal components.

Comparison of the efficacy of combined fluticasone propionate and olopatadine versus combined fluticasone propionate and fexofenadine for the treatment of allergic rhinoconjunctivitis induced by conjunctival allergen challenge.

BACKGROUND: One approach to treating allergic rhinoconjunctivitis is the concomitant use of an intranasal spray such as fluticasone propionate to alleviate nasal symptoms and a topical or systemic agent to relieve ocular symptoms. It has not yet been determined whether a topical or systemic agent is more effective for the latter purpose. OBJECTIVE: This study compared the efficacy of combined use of fluticasone and olopatadine with combined use of fluticasone and fexofenadine in the treatment of the signs and symptoms of allergic rhinoconjunctivitis. METHODS: This 2-site, randomized, double-masked, placebo-controlled, parallel-group study employed the conjunctival allergen challenge (CAC) model, a standardized method of inducing ocular and nasal signs and symptoms of allergic rhinoconjunctivitis. At visit 1, subjects underwent CAC to determine the dose of allergen required to elicit a positive reaction. The allergen dose was confirmed at visit 2, and, according to a randomization schedule, subjects were dispensed fluticasone, olopatadine, and placebo pill; fluticasone, fexofenadine, and tear substitute; or placebo nasal spray, placebo pill, and tear substitute. CAC took place at visit 3, after patients had used the assigned medications for 2 weeks. Study medication was instilled 2 hours before CAC, after which allergic signs and symptoms were graded on standardized scales. The primary efficacy variables were ocular itching, ocular redness, and overall nasal symptoms. RESULTS: Eighty subjects completed the study: 30 received fluticasone and olopatadine, 30 fluticasone and fexofenadine, and 20 placebo. Women constituted 63.8% of the study population and men 36.3%; 91.3% were white, 3.8% black, 2.5% Hispanic, 1.3% Asian, and 1.3% other. Concomitant use of fluticasone and olopatadine produced significantly greater improvements in ocular itching at 3 and 7 minutes after CAC compared with fluticasone and fexofenadine (P < 0.05). There were no significant differences in redness scores between groups; however, concomitant use of fluticasone and olopatadine produced significantly greater improvements in redness at 2 time points in each of the 3 vessel beds (ciliary, conjunctival, and episcleral) compared with placebo, and fluticasone and fexofenadine produced significantly greater improvement in redness at 1 time point in I vessel bed compared with placebo (both comparisons, P < 0.05). The 2 treatments had similar effects on total nasal symptom efficacy scores. CONCLUSIONS: In this study, concomitant use of the topical agents fluticasone and olopatadine was more effective than concomitant use of fluticasone plus fexofenadine for overall treatment of the signs and symptoms of induced allergic rhinoconjunctivitis.

The role of inhaled corticosteroids in asthma treatment: a health economic perspective.

Asthma affects approximately 23 million American children and adults, resulting in almost 15 million physician office and hospital visits, and nearly 2 million emergency department visits each year. Despite the publication of National Asthma Education and Prevention Program guidelines, asthma remains poorly controlled, with annual costs estimated at up to $56 billion. Current guidelines recommend long-term treatment with inhaled corticosteroids (ICS) because of their superior effectiveness in managing the chronic airway inflammation that characterizes persistent asthma. ICS monotherapy should be explored before alternatives such as leukotriene modifiers and long-acting beta agonists (LABAs) are attempted, especially after the US Food and Drug Administration's 2010 warning that LABAs should never be used alone to treat asthma due to the increased risk of severe exacerbations leading to hospitalization in both children and adults, with a possibility of death. In the past, asthma treatment focused solely on the central airways, rather than the small, more distant airways, and most traditional ICS therapies are aerosols which deliver large particles to the central airways. Today, the importance of the role of small airway disease in asthma, particularly inflammation, is known. Targeting the small airways may help improve clinical outcomes and reduce healthcare utilization and costs. The ICS beclomethasone dipropionate HFA does not require a spacer and is characterized by small particle sizes that result in more of the drug being deposited in both the large and small airways. Studies have demonstrated that beclomethasone dipropionate HFA is clinically effective and cost efficient compared with other asthma monotherapies or combination therapies.

Efficacy and central nervous system impairment of newer-generation prescription antihistamines in seasonal allergic rhinitis.

Allergic rhinitis is a highly prevalent disorder and oral antihistamines are often used to manage patient symptoms. Older-generation antihistamines, such as diphenhydramine and chlorpheniramine, are effective at relieving the symptoms of seasonal allergic rhinitis (SAR); however, they are associated with adverse events, including sedation and impairment, at, or above, the recommended dose. Newer-generation antihistamines, such as desloratadine, cetirizine and fexofenadine, were developed to minimize adverse events. In this article, studies examining newer-generation antihistamines in adults and children were reviewed. The clinical evidence confirms that desloratadine, cetirizine and fexofenadine are effective at managing the symptoms of SAR in adults and children; however, cetirizine is more likely to cause sedation. Physician intervention is paramount to SAR symptom management. It is essential that appropriate treatment relieves SAR symptoms with absent or minimal adverse events. This is particularly important for those patients involved in skilled and cognitive activities or safety-critical jobs.

First do no harm: managing antihistamine impairment in patients with allergic rhinitis.

Antihistamines are effective medications that have been used for decades in the management of allergic rhinitis; however, they may be administered or selected in an inappropriate fashion and may be the source of drug-related morbidity. Our objective is to present relevant background information and an expert consensus statement on the use of antihistamines in treatment of allergic rhinitis. In July 2002, 14 experts in allergy, clinical immunology, pharmacology, and impairment assessment were invited to participate in a roundtable conference to present current concepts and develop a consensus statement on the clinical management of allergic rhinitis with antihistamines. Many of the antihistamines used to treat allergic rhinitis, as well as the disease itself, may produce sedation, impairment, and reduced quality of life. Allergic rhinitis is more appropriately managed with the relatively nonimpairing second-generation antihistamines (eg, loratadine, desloratadine, cetirizine, and fexofenadine), because older agents (eg, diphenhydramine, chlorpheniramine, and brompheniramine) produce sedation and impairment and worsen sleep architecture. Although there is some debate surrounding the varying degrees of efficacy of second-generation antihistamines, it is known that some agents may produce varying levels of drowsiness or impairment, especially at higher than recommended doses. The differences with regard to safety among the second-generation antihistamines are smaller than are the differences between the first and second generations. A nonsedating, nonimpairing (even at higher than recommended doses), second-generation antihistamine is preferred for all patients, particularly those with a higher risk for the development of adverse effects. We recommend that primary care and specialist physicians, nurse practitioners, physician assistants, pharmacists, and all other health professionals involved in the diagnosis and treatment of allergic rhinitis follow this consensus document and share this information with patients for whom antihistamine therapy is recommended. In addition, further epidemiologic studies on the effects of antihistamines should be performed.