A randomized comparison of the effects of budesonide and mometasone furoate aqueous nasal sprays on nasal peak flow rate and symptoms in perennial allergic rhinitis.

BACKGROUND: Using conventional methods, it has been difficult to show differences in efficacy between intranasal corticosteroids in perennial rhinitis. OBJECTIVE: To compare the effects of budesonide and mometasone on nasal symptoms and nasal airflow in perennial allergic rhinitis. METHODS: Four hundred thirty-eight patients (age > 18 years old) were randomized to budesonide, 256 microg or 128 microg, mometasone furoate 200 microg, or placebo, once daily for 4 weeks. Efficacy was evaluated by nasal index score (NIS; the sum of scores for blocked nose, runny nose, and itchy nose/sneezing) and peak nasal inspiratory flow (PNIF). RESULTS: All three active treatments significantly reduced the NIS compared with placebo. There was no significant difference between the treatments, although the effect of budesonide, 256 microg, tended to be greater than that of the other regimens. PNIF was significantly improved with all three active treatments: the effect of budesonide 256 microg on morning and evening PNIF was significantly greater than that of mometasone furoate and 128 microg budesonide. Budesonide had a rapid onset of action, showing a significantly greater effect on evening PNIF than mometasone furoate during the first 10 days. For all active treatments, significant improvements in NIS were seen within 4 hours of the first dose. All three treatments were well tolerated. CONCLUSION: The objective parameter PNIF was capable of demonstrating greater efficacy of budesonide 256 microg compared with budesonide 128 microg and mometasone furoate 200 microg, whereas the combined nasal symptom score could only distinguish active treatment from placebo.     

Early treatment of perennial rhinitis with budesonide or cetirizine and its effect on long-term outcome

BACKGROUND: Perennial rhinitis is a common disease that has many similarities with bronchial asthma. Early treatment with inhaled steroids has improved asthma symptoms, lung function, and bronchial hyperreactivity, but it has not been studied in perennial rhinitis. OBJECTIVE: The main objective was to determine whether early introduction of long-term daily intranasal steroid treatment would have a positive effect on the clinical course and outcome of perennial rhinitis compared with the effect of an antihistamine. A secondary objective was to compare the clinical efficacy of intranasal budesonide and oral cetirizine. METHODS: One hundred forty-three adult patients with newly detected perennial allergic or nonallergic eosinophilic rhinitis of 1 to 3 years' duration were randomized to receive budesonide dry powder, 400 microg (delivered dose of 280 microg) intranasally, or cetirizine, 10 mg orally, once daily for 1 year. At the end of the double-blind treatment period, medication was stopped, and the patients were followed for another year, during which time they could use 14-day courses of intranasal budesonide as needed to control rhinitis relapses. The main outcome measures were the time to first relapse and the number of relapses during the second year. Nasal symptom scores, nasal smear eosinophilia, and nasal peak expiratory flow were used to compare the clinical efficacy of the 2 treatments. RESULTS: During the randomized phase of the study, budesonide was significantly more effective than cetirizine in relieving nasal symptoms. Nasal peak expiratory flow improved significantly in budesonide-treated patients compared with in patients receiving cetirizine. After discontinuation of randomized treatment, 38% of budesonide-treated and 56% of cetirizine-treated patients had a relapse within the first month (P =.04). The median time to first relapse was longer in budesonide-treated patients than in cetirizine-treated patients (62 vs 20 days), although the difference was not significant. Fourteen-day courses of budesonide provided effective control of relapses; the mean number of relapses was 4.0 versus 5.4 in the groups previously treated with budesonide or cetirizine, respectively. Both treatments were well tolerated throughout the study. CONCLUSIONS: Budesonide is significantly more effective than cetirizine in controlling perennial rhinitis. After stopping treatment, budesonide better prevents relapses for 1 to 2 months compared with cetirizine. Periodic therapy with budesonide may be sufficient to control symptoms in most patients who have relapses.     

Budesonide aqueous nasal spray is an effective treatment in children with perennial allergic rhinitis, with an onset of action within 12 hours.

BACKGROUND: Budesonide aqueous nasal spray is a topical corticosteroid which at doses of 64 to 256 microg once daily has been found to be effective in the treatment of seasonal allergic rhinitis in adults and children. OBJECTIVE: This study was conducted to determine the efficacy of budesonide aqueous nasal spray, 128 microg once daily, in children with perennial allergic rhinitis. METHODS: This double-blind, randomized, placebo-controlled, parallel-group, multicenter study compared the efficacy and safety of budesonide aqueous nasal spray, 128 microg once daily intranasally, with placebo in 202 patients (aged 6 to 16 years) with perennial allergic rhinitis. Efficacy was evaluated daily by measurement of peak nasal inspiratory flow (PNIF), nasal symptom scores over 12 hours, and an overall evaluation of treatment efficacy. In a subset of patients (n = 76), quality of life was measured by validated questionnaires. RESULTS: Budesonide, 128 microg once daily, was significantly more effective than placebo in improving the PNIF, combined and individual nasal symptom scores, and the overall evaluation of treatment efficacy. The onset of action was found to occur within the first 12-hour time interval evaluated for combined nasal symptoms and within 48 hours for PNIF. Budesonide was associated with reduced percentage of eosinophils in brush samples and reduced intake of rescue medication in comparison with placebo. Quality of life scores were reduced, but the differences did not reach significance. CONCLUSIONS: Budesonide aqueous nasal spray, 128 microg once daily, is effective in children with perennial allergic rhinitis. Efficacy was demonstrated within 12 hours.     

Growth velocity in children with perennial allergic rhinitis treated with budesonide aqueous nasal spray.

BACKGROUND: Recent guidelines recommend intranasal corticosteroids as first-line treatment for managing persistent symptoms of moderate to severe allergic rhinitis (AR). However, in children, long-term continual treatment with corticosteroids has raised concerns about potential growth suppression. OBJECTIVE: To evaluate the effects of the recommended once-daily dose of budesonide aqueous nasal spray on growth velocity, as measured with stadiometry, in children with perennial AR. METHODS: In this double-blind, placebo-controlled, multicenter study, 229 prepubertal children (mean age, 5.9 years; age range, 4-8 years) with perennial AR were randomized (2:1) to receive budesonide aqueous nasal spray, 64 microg (32 microg per nostril) once daily, or placebo for 1 year. The change from baseline in growth velocity, height after treatment, and the percentage of patients whose percentile for height decreased from baseline to the end of treatment were evaluated. RESULTS: Growth velocity was not significantly different between the 2 groups. The least-squares mean +/- SE growth velocity during treatment was 5.91 +/- 0.11 cm per year for children receiving budesonide and 6.19 +/- 0.16 cm per year for those receiving placebo. The mean difference in growth velocity between the 2 groups was 0.27 +/- 0.18 cm per year (95% confidence interval, -0.07 to 0.62 cm per year). After treatment, the mean +/- SD height was 128.8 +/- 8.7 cm for children receiving budesonide and 128.2 +/- 8.8 for those receiving placebo. The percentage of children whose percentile for height decreased during treatment was not significantly different between the 2 groups (budesonide, 59%, placebo, 54%; P = .64). The incidence and types of adverse events and the mean 24-hour urinary cortisol-creatinine ratio were similar for the 2 groups. CONCLUSIONS: Treatment with budesonide aqueous nasal spray, 64 microg once daily, for 1 year did not suppress growth velocity compared with placebo and was well tolerated in prepubertal children with perennial AR.     

Short-term lower leg growth rate in children with rhinitis treated with intranasal mometasone furoate and budesonide.

BACKGROUND: Mometasone furoate (MF) aqueous nasal spray is a potent intranasal glucocorticoid with low systemic bioavailability. Knemometry has been shown to be a sensitive method of detecting systemic effects of exogenous steroids in children. OBJECTIVE: We sought to assess whether MF (100 or 200 microg) or budesonide intranasal aqueous spray (400 microg) influences the short-term lower leg growth rate in children with seasonal or perennial allergic rhinitis. METHODS: MF, budesonide, and placebo were administered once daily for 2 weeks to 22 children aged 7 to 12 years (mean, 10 years) in a randomized, double-blind, crossover study. Lower leg measurements were done before and after each 2-week treatment period. Two-week washout intervals separated each treatment period. RESULTS: There were no significant differences in lower leg growth rates among the MF 200 microg (0.95 +/- 0.79 mm; mean +/- SD), budesonide 400 microg (0.73 +/- 0.61 mm), or placebo (0.69 +/- 0.70 mm) groups. The growth rate of the group receiving a 100-microg dose of MF (1.16 +/- 0.67 mm) was greater than that for the group receiving placebo (P =.024) or budesonide (P =.033). No statistically significant sequence effect (P =.11), carry-over effect (P =.24), overall treatment effect (P =.086), or period effect (P =.065) was detected. CONCLUSION: No short-term adverse effects on linear lower leg growth rates were detected after once daily MF or budesonide at clinically relevant doses.     

Long-term safety of fluticasone furoate nasal spray in adults and adolescents with perennial allergic rhinitis

BACKGROUND: Fluticasone furoate is a novel-enhanced affinity glucocorticoid and its long-term safety must be assessed. This study was designed to assess the safety and tolerability of 12-month intranasal administration of fluticasone furoate in adult and adolescent patients with perennial allergic rhinitis (PAR). METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study, 806 patients with PAR were randomized to once daily (od) fluticasone furoate nasal spray 110 microg (n = 605) or vehicle placebo nasal spray (n = 201) for 12 months, following a 7- to 14-day screening period. Safety was assessed by monitoring adverse events (AEs), 24-h urinary cortisol excretion, nasal and ophthalmic examinations, electrocardiograms and clinical laboratory tests. Plasma concentrations of fluticasone furoate were determined from blood samples. RESULTS: Fluticasone furoate was well tolerated. The incidence of most AEs was similar to that observed with placebo, with the exception of epistaxis, which was more frequently reported on active treatment. There were no clinically meaningful differences between fluticasone furoate and placebo in terms of safety assessments, including mean changes in ophthalmic parameters and 24-h urine cortisol excretion. Plasma concentrations of fluticasone furoate were not quantifiable in the majority of patients following intranasal administration. CONCLUSIONS: Long-term (12-month) administration of fluticasone furoate 110 microg od revealed an AE profile typical of the intranasal corticosteroid class in both adult and adolescent patients with PAR, with no evidence of clinically relevant systemic corticosteroid exposure.     

Intranasal budesonide for the treatment of perennial rhinitis in Thai patients

The efficacy and tolerability of a new intranasal glucocorticosteroid, budesonide, was evaluated in 28 Thai adult patients with perennial rhinitis. After one week pre-treatment observation period, the nasal spray was given as two puffs into each nostril twice daily (400 micrograms/day) for four weeks. The severity of all nasal symptoms decreased significantly after 1 week treatment reaching a minimal level after 2 weeks. The amounts of antihistamine tablets taken by the patients were also significantly reduced during the treatment with budesonide. Three patients reported adverse effects which were mild and easily tolerated. Morning plasma cortisol levels measured before and after four-week treatment in 15 patients revealed no significant changes. This study suggests that intranasal budesonide is an effective and well-tolerated treatment for perennial rhinitis.     

Efficacy and safety of intranasal budesonide in the treatment of perennial rhinitis in adults and children

The efficacy and safety of intranasal budesonide were evaluated in a placebo-controlled double-blind study of 51 children (6 to 18 years) and 48 adults with perennial (allergic or nonallergic) rhinitis. The trial commenced with a 2-week baseline period without treatment for perennial rhinitis. This was followed by a treatment period of 4 weeks. Treatment was either intranasal budesonide 200 micrograms bid or matching placebo bid. Nasal symptoms were rated daily on a scale from 0 (absent) to 3 (severe). Safety was monitored by laboratory assessments (hematology, blood chemistry, urinalysis) as well as by rhinoscopy and recording of adverse events. Budesonide reduced the nasal symptoms as compared with baseline. The reduction was greater than in the placebo group and symptoms were improved significantly on budesonide treatment compared with placebo. Laboratory assessments demonstrated no differences between budesonide and placebo. Adverse responses to intranasal budesonide were few and minor, and compliance was high. Intranasal budesonide, 200 micrograms bid, thus appears to be efficacious, highly acceptable, and safe for the treatment of perennial rhinitis.     

Dose-dependent effects of budesonide aqueous nasal spray on symptoms in a daily nasal allergen challenge model.

BACKGROUND: It has been difficult to demonstrate dose-dependent clinical effects of anti-allergic glucocorticosteroid drugs in allergic rhinitis. OBJECTIVE: To determine dose-dependent effects on rhinitis symptoms of clinical doses of the glucocorticosteroid budesonide in a standardized daily allergen challenge model. METHODS: Twenty-five patients with seasonal allergic rhinitis were examined outside the pollen season. The highest 256 microg once daily and lowest 64 microg once daily clinically recommended doses of budesonide aqueous nasal spray and placebo were given in a double-blind, placebo-controlled, randomized, and crossover design with 4 weeks' washout between treatments. After 1 week's treatment, the patients received individually titrated nasal allergen challenges once every morning for 8 days while treatment continued. Nasal symptoms were scored in diary cards. Nasal symptoms from the 6th to the 8th challenge days were used in the analysis. RESULTS: The provocation model produced clinically relevant, and around the clock well tolerable rhinitis symptoms, suggesting that after several days of repeated allergen challenges, a season-like, transient allergic disease condition had been established. Both 64 microg and 256 microg of budesonide aqueous nasal spray reduced nasal symptoms. Budesonide 64 microg reduced total nasal symptoms scores from 5.19 +/- 0.5 to 4.23 +/- 0.53 (P < .05), and budesonide 256 microg reduced total nasal symptoms scores to 3.41 +/- 0.51 (P < .001). A significant difference in nasal symptoms after challenge between budesonide aqueous nasal spray 64 microg and 256 microg (P = .03), indicated a dose-dependent effect. CONCLUSIONS: A dose-dependent, symptom-reducing effect of once-daily treatment with topical aqueous nasal sprays of budesonide for two weeks was demonstrated, suggesting that this model is relevant for assessments of dose-dependent effects of anti-inflammatory drugs.     

Cost-effectiveness analysis of budesonide aqueous nasal spray and fluticasone propionate nasal spray in the treatment of perennial allergic rhinitis.

BACKGROUND: An economic evaluation was performed analyzing direct medical costs in Canada for the treatment of perennial allergic rhinitis (PAR) with budesonide aqueous nasal spray and fluticasone propionate nasal spray. Three hundred fourteen patients with at least a 1-year history of PAR were randomized into a double-blind, parallel-group study of 6 weeks' duration. The treatments were daily doses of budesonide 256 microg, fluticasone propionate 200 microg, or placebo. Both active treatments produced significantly lower mean scores for overall nasal symptoms compared with placebo, and both were well tolerated. Budesonide was significantly more effective than fluticasone in reducing "blocked nose." METHOD: A retrospective cost-effectiveness analysis utilizing the clinical trial data was performed on the total costs of (1) budesonide-based and (2) fluticasone-based treatment strategies, including the relative importance of the drug costs in both strategies. RESULTS: The average treatment cost per patient in Canada over 12 months in the budesonide group was CAD 389.85 which was 23.3% lower than in the fluticasone group, which was CAD 508.06, due to lower drug acquisition costs (for the year 1998). CONCLUSION: Budesonide aqueous nasal spray was shown to be more cost-effective than fluticasone propionate nasal spray in the treatment of perennial allergic rhinitis. This result is valid in the province of Ontario, Canada and in many other settings with the same structure of relative prices. The result is mainly driven by a difference in drug cost.     

Long-term safety of budesonide nasal aerosol: a 5.5-year follow-up study

The effects of prolonged treatment with intranasally applied budesonide was studied in twenty-four patients with perennial allergic or non-allergic rhinitis. Patients on continuous treatment were followed up for 5.5 years. At entry and follow-up visits, rhinoscopic findings, nasal symptom scores, blood chemistry, haematology, urine analysis and determination of plasma cortisol levels, before and after stimulation with ACTH (Synacthen®, Ciba-Geigy AG, Basel, Switzerland), were registered. Biopsies of the nasal mucosa were taken before entry into the study, after 1 year of treatment, and after varying time intervals ranging from 2.5 to 5.5 years during the treatment. The biopsy specimens were examined blindly by an independent pathologist. The analyses revealed no histopathological changes in the nasal mucosa. All nasal symptom parameters assessed by the patients were significantly reduced from the baseline during the entire follow-up period. No clinically significant changes in the haematological and blood chemistry parameters were observed. Plasma cortisol analyses before and after challenge with ACTH revealed no influence on the hypothalamic pituitary adrenal (HPA) axis. The present study suggests that intranasal budesonide in the dose of 200–400 μg/day is also a safe treatment for prolonged treatment of perennial rhinitis.     

Establishing a model of seasonal allergic rhinitis and demonstrating dose-response to a topical glucocorticosteroid.

BACKGROUND: Symptoms of seasonal allergic rhinitis may vary greatly. Hence, for research purposes, there is a need for disease-like models of allergic rhinitis. In a preliminary study, involving 7 days' challenge with allergen, promising symptom consistency was obtained and dose-response to a glucocorticosteroid could, in part, be demonstrated. OBJECTIVE: To establish this model of seasonal allergic rhinitis and test the hypothesis that mometasone furoate is more potent than budesonide as an antirhinitis drug. METHODS: Thirty-eight patients with seasonal allergic rhinitis received treatment with spray-formulations of placebo, budesonide 64 microg, budesonide 256 microg, and mometasone furoate 200 microg in a double-blind, crossover design. After 3 days' treatment, individualized nasal allergen-challenges were administered daily for 7 days while the treatment continued. Nasal symptoms and peak inspiratory flow (PIF) were recorded. RESULTS: During the last 3 days of allergen challenge without active treatment, consistent around-the-clock symptoms were recorded and recordings during these days were used in the analysis. With few exceptions the active treatments reduced nasal symptoms and improved nasal PIF (P values <0.001 to 0.05). Budesonide caused dose-dependent improvements in evening symptoms, morning nasal PIF, and nasal PIF recorded 10 minutes after allergen-challenge (P values <0.05). Budesonide 256 microg produced greater improvement than mometasone furoate 200 microg for nasal PIF 10 minutes after allergen-challenge (P < 0.05). CONCLUSION: The present allergen challenge method, producing consistent symptoms and nasal PIF data, emerges as a model of seasonal allergic rhinitis well suited for exploring potency and efficacy of drug intervention. The present data do not support the view that mometasone furoate is a more potent antirhinitis drug than budesonide.     

Impact of Inhaled and Intranasal Corticosteroids on the Growth of Children

Since inhaled and intranasal corticosteroids may be systemically bioavailable, risk of growth suppression cannot be ruled out in children treated with these compounds. The mechanisms by which exogenous corticosteroids can cause growth suppression may be multifactorial, involving influences on growth hormone secretory profiles and insulin-like growth factor-I activity, direct effects on the epiphyseal growth plate, and effects on bone and collagen turnover. When studies on growth in children treated with inhaled and intranasal corticosteroids are interpreted, it is important to discriminate between data on the final outcome of growth (adult height) and data on growth rate. No firm conclusions can be drawn on adult height from the available data. While the data on children treated with inhaled corticosteroids appear reassuring, there are no peer-reviewed studies on the final height of children treated with intranasal corticosteroids. The possibility of additive effects on the final height or growth rate of children receiving intranasal plus inhaled corticosteroids has also not been studied. When assessing the risk of growth rate suppression, specific corticosteroids, doses and inhaler systems must be evaluated separately. Standard paediatric doses of inhaled corticosteroids (budesonide 200 to 400 microg/day delivered from a metered dose inhaler with a spacer, dry powder budesonide 200 microg/day, or dry powder fluticasone propionate 200 microg/day) do not affect growth rate when a twice daily administration regimen is used. The risk of growth rate suppression in children treated with inhaled budesonide depends on the dosage and may become significant with 800 microg/day administered with a spacer, or with 400 microg/day administered with a dry powder device. When high doses of inhaled corticosteroids are used, the risk of adverse effects on growth rate can be reduced by once daily dosage in the morning. In fact, intranasal mometasone furoate 100 and 200microg from an aqueous pump spray and dry powder budesonide 200 and 400microg once daily in the morning have been found not to affect growth rate. Sensitivity to adverse effects on growth rate may vary between individuals. If growth suppression is detected, 'catch-up growth' may be expected when the dose of the inhaled or intranasal corticosteroid is reduced or other treatment modalities are introduced. Inhaled or intranasal corticosteroids should not be withheld from children with asthma or rhinitis. Topical corticosteroids should be given in doses that control disease symptoms; however, height measurements should be performed regularly in children receiving corticosteroids.     

The effect of budesonide on the cytokine pattern in patients with perennial allergic rhinitis.

BACKGROUND: A T(H)2-polarized cytokine pattern has been demonstrated in allergic rhinitis. Budesonide represents an effective topical corticosteroid in the management of allergic rhinitis. OBJECTIVE: To evaluate cytokine pattern and symptoms in patients with perennial allergic rhinitis before and after treatment with intranasal budesonide. METHODS: All patients received budesonide aqueous nasal spray or placebo for 2 weeks. The study was double-blind, parallel group, placebo controlled, and randomized. Nasal lavage was performed in all patients before and after treatment. A panel of cytokines, including interleukin 4 (IL-4), IL-5, and IL-6, was measured by immunoassay on fluids recovered from nasal lavage. Total symptom score (including rhinorrhea, nasal itching, sneezing, and nasal obstruction) was evaluated before and after treatment. RESULTS: Twenty patients with perennial allergic rhinitis were evaluated (13 men and 7 women; mean age, 24.7 years). Budesonide aqueous nasal spray treatment showed a significant decrease of IL-4 (P = .007), IL-5 (P = .04), and IL-6 levels (P = .009). Budesonide aqueous nasal spray treatment also induced significant symptom relief (P = .006). Placebo treatment did not significantly affect the evaluated parameters. CONCLUSIONS: This study shows that budesonide aqueous nasal spray is effective in exerting immunomodulatory activity by reducing cytokine pattern and relieving symptoms. These findings are evidence of the effects of intranasal budesonide in treating perennial allergic rhinitis.     

A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma

BACKGROUND: Allergic rhinitis and asthma commonly coexist and are both mediated by similar inflammatory mechanisms. Leukotriene antagonists may therefore be an alternative to corticosteroid therapy. OBJECTIVE: To compare oral montelukast with inhaled plus intranasal budesonide in patients with seasonal allergic rhinitis and asthma. PATIENTS AND METHODS: A single-blind double-dummy placebo-controlled crossover study was performed comparing once daily 10 mg oral montelukast with 400 microg inhaled plus 200 microg intranasal budesonide in 12 patients with allergic rhinitis and asthma: mean (S.E.) age 34.0 years (2.7), forced expiratory volume in 1 s (FEV1) 91.2 (3.8)% predicted. Each treatment was for 2 weeks with a 1-week placebo run-in and washout. Measurements were made after each active treatment and placebo for: adenosine monophosphate bronchial challenge, exhaled and nasal nitric oxide. Patients also recorded their domiciliary peak expiratory flow, nasal peak inspiratory flow, asthma and seasonal allergic rhinitis symptoms. RESULTS: There were no significant differences between the placebos for any measurement. For adenosine monophosphate PC20, geometric mean fold differences (95% confidence interval (CI) for difference) were 6.4 (2.2-18.6) for placebo vs. budesonide, 2.9 (1.0-8.4) for placebo vs. montelukast, and 2.1 (1.1-4.5) for budesonide vs. montelukast. For exhaled nitric oxide (p.p.b.) there was significant (P < 0.05) suppression with both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For nasal nitric oxide and nasal peak flow there were only significant differences with budesonide compared with placebo. Both treatments reduced total seasonal allergic rhinitis symptoms but only budesonide had a significant effect on nasal symptoms. CONCLUSION: Once-daily inhaled plus intranasal budesonide and once daily montelukast showed comparable efficacy on lower airway, but only the budesonide had significant efficacy on upper airway inflammatory markers. Both treatments significantly reduced allergic rhinitis symptoms.     

Long-Term Safety and Efficacy of Budesonide Nasal Aerosol in Perennial Rhinitis

A long-term safety study of intranasally administered budesonide, a topical glucocorticoid, has been performed. 104 patients with perennial rhinitis, allergic or non-allergic, participated in a multicentre study in seven ENT-clinics utilising an identical protocol. A budesonide dosage of 400 μg/day was used as starting dose, but the patients were at liberty to reduce the daily dose to 200 μg. The patients were observed at intervals up to 12 months. At the entry and follow-up visits the following parameters were recorded: rhinoscopic findings, nasal symptom scores, blood chemistry, hematology, urinalysis and determination of plasma cortisol levels before and after stimulation with ACTH (Synacthen®). Nasal biopsies taken from 50 of the patients at the beginning and completion of the study were examined in a blinded way by an indepndent pathologist. The analysis revealed no histopathological changes of the nasal mucosa. At rhinoscopy no signs of atrophy or Candida were reported. Lividity of the nasal mucosa was significantly reduced during the trial, which was also the case for nasal congestion and secretion. All nasal symptom parameters assessed by the patients were significantly reduced from baseline during the follow-up period. No clinically significant changes in the hematological and blood chemistry parameters were observed. Plasma cortisol analysis before and after challenge with ACTH revealed no influence on the hypothalamic pituitary adrenal axis. No tachyphylaxis was observed; on the contrary, there was a clear tendency for reduction of the daily dose of budesonide necessary to keep the patients symptom-free. The present study suggests that intransal budesonide in the dose of 400 μg/day is a safe and valuable addition to our therapeutic armory for perennial rhinitis.     

Long-term safety and efficacy of intranasal ciclesonide in adult and adolescent patients with perennial allergic rhinitis.

BACKGROUND: Ciclesonide is a corticosteroid in development for allergic rhinitis that has been shown to be safe and effective in seasonal allergic rhinitis and perennial allergic rhinitis (PAR) trials of up to 6 weeks in duration. However, the long-term safety and efficacy of ciclesonide are unknown. OBJECTIVE: To demonstrate the long-term safety of intranasal ciclesonide, 200 microg once daily, in patients with PAR. METHODS: Patients (> or = 12 years old) with a 2-year or longer history of PAR were randomized in a double-blind fashion to receive ciclesonide, 200 microg, or placebo once daily in the morning for up to 52 weeks. Spontaneous and elicited adverse events were monitored throughout the study. Ear, nose, and throat examinations were performed to evaluate local tolerability. Additionally, 24-hour urinary free cortisol level, morning plasma cortisol level, intraocular pressure, and lens opacification were monitored to evaluate the systemic safety of intranasal ciclesonide. Ciclesonide efficacy was determined by measuring 24-hour reflective total nasal symptom scores. RESULTS: No clinically relevant differences were observed between the ciclesonide and placebo groups in adverse events, ear, nose, and throat examinations, or 24-hour urinary free or morning plasma cortisol levels. Similarly, no clinically relevant differences were found between treatment groups in intraocular pressure, visual acuity, or lens opacification. With regard to efficacy, ciclesonide achieved a significantly greater reduction in 24-hour reflective total nasal symptom score compared with placebo over more than 52 weeks (P < .001). CONCLUSION: In this study, intranasal ciclesonide, 200 microg once daily, was safe and effective for the long-term treatment of PAR, with no evidence of tachyphylaxis.     

Knemometric assessment of systemic activity of once daily intranasal dry-powder budesonide in children

Systemic activity of the intranasal glucocorticosteroid budesonide administered once daily from a dry-powder inhaler (Turbuhaler®) was assessed by knemometry. Lower leg length was measured weekly in 38 children aged 7–15 (mean 11.3) years with allergic or perennial rhinitis. The design was a randomized, double-blind, parallel-group study. After 4 weeks' run-in, the children were allocated to 4 weeks' treatment with either budesonide 200 or 400 μg or placebo. Fourteen children in the budesonide 200-μg group, 13 in the 400-μg group, and 10 in the placebo group completed the study. In the placebo and budesonide 200-μg groups, growth velocities during run-in (0.36 and 0.28 mm/week, respectively) and treatment periods (0.34 and 0.27 mm/week, respectively) were almost identical. In the budesonide 400-μg group (run-in: 0.40 mm/week), a nonsignificant reduction in mean growth velocity of 0.18 mm/week was seen ( P = 0.11). There were no statistically significant differences among the run-in mean lower leg growth velocities (F= 1.12; P = 0.34), among growth velocities during treatment (F= 1.10; P = 0.34), or among the run-in and treatment growth velocities in the three groups (F= 1.19; P = 0.32). These results provide good evidence that systemic activity is low in children with allergic or perennial rhinitis treated with once daily budesonide in doses of 200- and 400-μg administered intranasally from a dry-powder inhaler.     

Effect of budesonide aqueous nasal spray on hypothalamic-pituitary-adrenal axis function in children with allergic rhinitis.

BACKGROUND: Intranasal corticosteroids are safe and effective for treating allergic rhinitis in adults. Since children may receive more systemic corticosteroid on a dose-per-weight basis than adults, the safety of corticosteroid therapy in pediatric patients is an important issue. OBJECTIVE: To determine the effects of treatment with budesonide aqueous nasal spray using the recommended once-daily dose for adults and children 6 years and older on hypothalamic-pituitary-adrenal (HPA) axis function in pediatric patients with allergic rhinitis. METHODS: In a 6-week, multicenter, double-blind, placebo-controlled study, 78 patients aged 2 to 5 years with allergic rhinitis were treated with budesonide aqueous nasal spray (64 microg/d) or placebo. Mean change in morning plasma cortisol levels from baseline to study end 0, 30, and 60 minutes after low-dose (10-microg) cosyntropin stimulation and mean change in the difference from 0 to 30 minutes and from 0 to 60 minutes after cosyntropin stimulation were used to evaluate HPA axis function. RESULTS: Mean change from baseline to study end in plasma cortisol levels 0, 30, and 60 minutes after cosyntropin stimulation and the difference from 0 to 30 minutes and from 0 to 60 minutes were not significantly different between the treatment and placebo groups (P > .05 for all). At the end of the study, 3 budesonide aqueous nasal spray and 6 placebo patients were classified as having subnormal HPA axis function. The safety and tolerability profile of budesonide aqueous nasal spray was comparable to that of placebo. CONCLUSIONS: Administration of budesonide aqueous nasal spray for 6 weeks was well tolerated and safe and had no measurable suppressive effects on HPA axis function in patients aged 2 to 5 years with allergic rhinitis.     

Comparison of the efficacy of budesonide and fluticasone propionate aqueous nasal spray for once daily treatment of perennial allergic rhinitis

Background: Intranasal corticosteroids, such as budesonide and fluticasone propionate, are widely prescribed in the treatment of perennial allergic rhinitis. Once daily budesonide dry powder and fluticasone propionate aqueous suspension have been found to provide similar efficacy in controlling symptoms of perennial allergic rhinitis. Objective: The purpose of this study was to assess the efficacy and safety of treatment with once daily budesonide aqueous nasal spray. Methods: This study involved a multicenter, blinded, randomized, parallel-group, placebo-controlled trial of adults with perrenial allergic rhinitis. Patients (n = 273) recorded daily nasal symptoms for 8 to 14 days (baseline) and 6 weeks (treatment). Results: Budesonide decreased combined symptoms to a significantly greater extent than did fluticasone (P = .03); both treatments significantly decreased mean combined nasal symptoms scores compared with placebo. Of the 3 nasal symptoms assessed (ie, nasal blockage, runny nose, and sneezing), nasal blockage was significantly (P = .009) more decreased with budesonide compared with fluticasone. Both treatments also significantly improved runny nose and sneezing compared with placebo. Improvement in combined nasal symptom scores of the budesonide-treated group reached statistical significance within 36 hours compared with placebo (P = .01); in those patients treated with fluticasone, significant improvement compared with placebo was first observed within 60 hours. Adverse events were mild and transient. Conclusions: Once daily budesonide aqueous nasal spray, 256 μg, was significantly better in controlling the symptoms of perrenial allergic rhinitis than once daily fluticasone propionate, 200 μg, especially nasal blockage. Both treatments were superior to placebo. Budesonide may have a faster onset of action than fluticasone. (J Allergy Clin Immunol 1998;102:902-8.)