Melissa A. Faris

Fluticasone propionate aqueous nasal spray provided significantly greater improvement in daytime and nighttime nasal symptoms of seasonal allergic rhinitis compared with montelukast

BACKGROUND The safety and efficacy of intranasal corticosteroids for the treatment of allergic rhinitis is well documented in the literature. Additionally, an expert panel has concluded that intranasal corticosteroids are the first line of therapy when obstruction is a major component of rhinitis. Montelukast is a leukotriene receptor antagonist recently approved for the treatment of seasonal allergic rhinitis (SAR). OBJECTIVE This randomized, double-blind, double-dummy, parallel-group study was conducted to compare the effectiveness of a 15-day course of intranasal fluticasone propionate 200 microg, once daily (FP200QD), to oral montelukast 10 mg, once daily (MON10QD), in relieving daytime and nighttime nasal symptoms associated with SAR. METHODS The intent-to-treat (ITT) analysis population consisted of 705 eligible males and females (> or = 15 years) with SAR randomized to either FP200QD (N = 353) or MON10QD (N = 352). The primary efficacy endpoint was the mean change from baseline in subject-rated daytime total nasal symptom scores (the sum of four individual scores: nasal congestion, itching, rhinorrhea, and sneezing), evaluated via visual analog scales, and averaged over weeks 1 to 2. Secondary endpoints included the four daytime individual nasal symptom scores, the nighttime total, and individual nasal symptom scores (each evaluated on a four-point scale from 0 to 3). RESULTS Statistically significant differences favoring FP200QD over MON10QD were observed for the mean change from baseline in daytime total nasal symptom scores (P < 0.001), daytime individual nasal symptom scores (P < 0.001), nighttime total (P < 0.001), and all individual nasal symptom scores (P < or = 0.002) over the 15-day treatment period. FP200QD and MON10QD were both well tolerated. CONCLUSIONS The results of this well controlled study demonstrated that FP200QD was consistently superior to MON10QD with regard to every efficacy endpoint evaluated, including daytime and nighttime nasal congestion, in subjects with SAR.

Efficacy and safety of inhaled fluticasone propionate chlorofluorocarbon in 2- to 4-year-old patients with asthma: results of a double-blind, placebo-controlled study

BACKGROUND Current asthma guidelines recommend inhaled glucocorticoids administered via pressurized metered-dose inhaler (MDI) with a holding chamber as the preferred therapy for young children with asthma. OBJECTIVE To evaluate the efficacy and safety of fluticasone propionate chlorofluorocarbon MDI use in preschool-aged children with asthma. METHODS Randomized, double-blind, placebo-controlled, parallel-group study of 332 children aged 24 to 47 months with asthma. Fluticasone propionate chlorofluorocarbon, 44 or 88 microg twice daily, or placebo (chlorofluorocarbon propellant alone) administered for 12 weeks via MDI with a valved holding chamber and an attached face mask. The primary efficacy measure was average change in 24-hour daily asthma symptom scores. Safety assessments included adverse events, 12-hour urinary cortisol excretion, and growth. RESULTS Treatment failure (ie, asthma exacerbation) occurred in approximately half as many fluticasone propionate-treated patients (13%-14%) as placebo-treated patients (24%). Compared with placebo users, patients treated with fluticasone propionate, 88 microg twice daily, had a 13% greater improvement in the mean proportion of symptom- and albuterol-free days (P = .02); asthma symptom scores and albuterol use were also significantly reduced. Patients treated with fluticasone propionate, 44 microg twice daily, had greater improvements than placebo-treated patients; however, differences did not reach statistical significance. At end point, the growth velocities of fluticasone propionate-treated patients were within the range of those of placebo-treated patients. No clinically relevant changes in 12-hour overnight urinary cortisol excretion were observed. CONCLUSION Compared with placebo use, fluticasone propionate, 88 microg administered twice daily, significantly reduced asthma exacerbations, asthma symptoms, and rescue albuterol use and was well tolerated, with no clinically relevant systemic effects, as measured by growth velocity or 12-hour urinary cortisol excretion levels.

Comparison of fluticasone propionate aqueous nasal spray and oral montelukast for the treatment of seasonal allergic rhinitis symptoms.

BACKGROUND Few studies have directly compared the efficacy of intranasal corticosteroids with that of leukotriene receptor antagonists for the treatment of daytime and nighttime symptoms of seasonal allergic rhinitis (SAR). OBJECTIVE To compare fluticasone propionate aqueous nasal spray, 200 microg daily, with oral montelukast, 10 mg daily, for the relief of SAR symptoms. METHODS Patients with SAR 15 years or older were randomized to receive either fluticasone propionate (n = 367) or montelukast (n = 369) in this double-blind, double-dummy, parallel-group study. The primary efficacy measure was the mean change from baseline in daytime total nasal symptom scores (TNSSs) (the sum of 4 daytime individual nasal symptom scores [INSSs] assessing nasal congestion, itching, rhinorrhea, and sneezing), averaged across weeks 1 and 2. Secondary efficacy measures included the 4 daytime INSSs, nighttime TNSSs (the sum of 3 nighttime INSSs assessing congestion on awakening, difficulty going to sleep, and nighttime awakenings), and the 3 nighttime INSSs averaged across weeks 1 and 2. RESULTS Mean changes from baseline in daytime TNSSs (P < .001), all daytime INSSs (P < .001), nighttime TNSSs (P < .001), and all nighttime INSSs (P < or = .02) showed significant differences favoring fluticasone propionate over montelukast across 2 weeks of treatment. CONCLUSION Compared with montelukast, fluticasone propionate provided significantly greater improvement in daytime and nighttime SAR symptoms.

Lack of effect on adult and adolescent hypothalamic-pituitary-adrenal axis function with use of fluticasone furoate nasal spray

BACKGROUND Intranasal corticosteroids are recommended as first-line therapy for allergic rhinitis (AR), and because of their pharmacologic class, hypothalamic-pituitary-adrenal (HPA) axis function is evaluated. OBJECTIVE To evaluate whether cortisol production was suppressed (as a measure of HPA axis function) by 6 weeks of treatment with fluticasone furoate nasal spray, 110 microg once daily, in patients with perennial AR. METHODS A double-blind, randomized, placebo- and active-controlled (prednisone), parallel-group study. Outpatients aged 12 to 65 years with perennial AR for 2 years or more were from 1 center in the United States and 1 center in Canada. Pharmacodynamic and pharmacokinetic samples were collected during 24-hour domiciled visits (overnight in clinic). Measurements included change from baseline in 24-hour serum cortisol weighted mean and 24-hour urinary free cortisol excretion, total 24-hour urinary free cortisol excretion and 6-beta hydroxycortisol excretion, and plasma concentration of fluticasone furoate. RESULTS A total of 112 of 183 patients were randomized. Fluticasone furoate was noninferior to placebo with respect to the ratio from baseline in serum cortisol weighted mean (treatment ratio, 0.98; 95% confidence interval, 0.89 to 1.07). In contrast, use of prednisone, 10 mg once daily, significantly reduced the ratio from baseline compared with placebo. Change from baseline in 24-hour urinary cortisol excretion was similar in the fluticasone furoate and placebo groups. Plasma levels of fluticasone furoate were undetectable after 6 weeks of treatment. CONCLUSION Fluticasone furoate nasal spray, 110 microg once daily, was not associated with HPA axis suppression in patients 12 years and older with perennial AR.

Albuterol HFA is as effective as albuterol CFC in preventing exercise-induced bronchoconstriction

BACKGROUND Secondary to the phase-out of chlorofluorocarbons (CFCs), the albuterol (Ventolin, GlaxoSmithKline, Uxbridge, Middlesex, United Kingdom) pressurized metered-dose inhaler (MDI) has been formulated in a non-ozone-depleting propellant, hydrofluoroalkane (HFA) 134a. OBJECTIVE To compare the efficacy of albuterol HFA to albuterol CFC and placebo HFA in protecting patients from exercise-induced bronchospasm (EIB). METHODS Randomized, double-blind, placebo-controlled, three-way crossover study in patients with documented EIB. Patients (n = 24) aged 18 to 45 years old received albuterol HFA or albuterol CFC, (total dose of 180 microg ex-actuator), or placebo HFA via an MDI, 30 minutes before a standardized exercise challenge. Serial forced expiratory volume in 1 second (FEV1) measurements were made 5 minutes before exercise and 5, 10, 15, 20, 25, 30, and 60 minutes postexercise. The primary outcome measure was the maximum percentage fall in FEV1 over the 60 minutes after exercise. RESULTS The adjusted mean maximum percentage falls in FEV1 postexercise for albuterol HFA and CFC groups were 15.4% and 14.9%, respectively. The two formulations were comparable with a treatment difference of -0.5% (P = 0.848; 95% confidence interval, -5.3 to 4.4%). When compared with the fall in FEV1 for placebo (33.7%), both active treatments demonstrated a significantly smaller fall in FEV1 postexercise (P < 0.001). Safety profiles were similar among the three treatment groups. CONCLUSIONS The results provide assurance to prescribers that the formulation of albuterol in the non-ozone-depleting propellant HFA 134a has not affected its efficacy in the treatment of EIB in asthmatic patients. Single doses of albuterol HFA and CFC from an MDI are comparable in terms of efficacy and safety on a microgram per microgram basis.

Treatment and Prophylaxis of Disseminated Mycobacterium Avium Complex in HIV-Infected Individuals

OBJECTIVE: To review the pathophysiology, epidemiology, treatment, and prophylaxis of disseminated Mycobacterium avium complex (MAC) infection in HIV-infected individuals. DATA SOURCES: A MEDLINE (January 1966–July 1997) and AIDSLINE (January 1980–July 1997) search of basic science articles pertinent to the MAC infection in HIV-infected patients. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: The organism, epidemiology, and pathophysiology of disseminated MAC are discussed for background. A review of clinical trials for the treatment and prophylaxis of disseminated MAC are presented, along with unresolved issues concerning these topics. CONCLUSIONS: The incidence of disseminated MAC has increased dramatically with the AIDS epidemic. The infection can lead to increased morbidity and mortality in HIV-infected patients. Treatment regimens for patients with a positive culture for MAC from a sterile site should include two or more drugs, including clarithromycin. Prophylaxis against disseminated MAC should be considered for patients with a CD4 cell count of less than 50/mm3.