Assessment of the efficacy and safety of three dose levels of cetirizine given once daily in children with perennial allergic rhinitis

The present study compared the efficacy and safety of three dose levels of cetirizine (2.5. 5, and 10 mg) once a day with placebo over 14 days in 6–12-year-old children with perennial allergic rhinitis. The design was a double-blind, randomized, multicenter, parallel-group study. Five symptoms (sneezing, nasal discharge, nasal obstruction, nasal pruritus, and ocular pruritus) were rated according to severity by investigators at the visits and daily by patients. Eighty-three patients were randomized to placebo, 84 to 2.5 mg cetirizine, 85 to 5 mg cetirizine, and 76 to 10 mg cetirizine. Groups were comparable at inclusion. The primary efficacy variable was the percentage of days with no or only mild symptoms: at all doses, cetirizine appeared to be more effective than placebo, but a significant difference was reached only in the 10-mg group (difference in medians of 22%; P = 0.016). The test of linearity was significant ( P = 0.026) for the percentage of asymptomatic days. The investigators' assessments at each visit scored the symptoms in the placebo group higher, i.e., more severe, than in the active groups, the 10-mg dose causing the greatest reduction in symptoms. Adverse events were infrequent and generally mild or moderate in severity. It was concluded that cetirizine at a 10-mg, once daily dose could be used to treat effectively 6–12-year-old children with perennial allergic rhinitis.     

Treatment of ragweed hay fever with intranasally administered disodium cromoglycate*

In a double-blind study the therapeutic effect of a 4% disodium cromoglycate (DSCG) nasal solution was evaluated in thirty-nine patients with acute symptoms of ragweed hay fever. Patients were randomly assigned to the DSCG or placebo group as they presented with allergic rhinitis. Overall, the DSCG was not more effective than placebo in controlling the symptoms of rhinitis or in decreasing the need for concomitant antihistamines or corticosteroids. Among patients with the highest pretreatment serum ragweed-specific IgE (RW IgE) levels, drug-treated patients had some reduction in symptoms as compared to their placebo controls during the peak of the ragweed pollen season. DSCG treatment did not influence the usual seasonal rise in RW IgE. Side effects from both the active and placebo aerosols were frequent but mild. We conclude that DSCG nasal solution used for the treatment of seasonal ragweed allergic rhinitis is relatively ineffective.     

Efficacy and safety of levocetirizine on symptoms and health-related quality of life of children with perennial allergic rhinitis: a double-blind, placebo-controlled randomized clinical trial.

BACKGROUND: This randomized study examined the efficacy and safety of levocetirizine in pediatric patients with perennial allergic rhinitis. Health-related quality of life (HRQL) was also investigated, which is particularly relevant in children because of the effects of rhinitis on learning, social activities, and comorbidity. OBJECTIVE: To evaluate the effect of levocetirizine on the Total 4 Symptoms Score, the 50% response rate, the Pediatric Rhinitis Quality of Life Questionnaire (PRQLQ), and investigators' global evaluation of symptom improvement. METHODS: Double-blind, placebo-controlled, randomized, multicenter trial of levocetirizine, 5 mg once daily for 4 weeks, in 306 children with perennial allergic rhinitis aged 6 to 12 years. There were 154 children in the levocetirizine arm and 152 in the placebo group who completed daily diary cards, and the PRQLQ and investigators' global evaluations were conducted at 3 visits. RESULTS: The levocetirizine group showed a significant improvement in 2-week and 4-week Total 4 Symptoms Score compared with placebo (P = .001 and P = .008, respectively). The 50% response rate for the first 2 weeks was 12.3% for the levocetirizine group compared with 3.9% for the placebo group (P = .01). The investigators' global evaluation also favored levocetirizine, because 57.1% of the children in the levocetirizine group were considered markedly or moderately improved compared with 44.7% in the placebo group. Levocetirizine also provided a significantly greater HRQL improvement than placebo at 2 weeks (P = .01), and the frequency of adverse events did not differ significantly from those seen in the placebo group. CONCLUSION: The study confirmed the efficacy of levocetirizine in relieving symptoms of perennial allergic rhinitis in children between 6 and 12 years of age. A HRQL benefit greater than placebo was shown. The treatment was well tolerated.     

The effect of sodium cromoglycate on the antigen-induced nasal reaction in allergic rhinitis as measured by rhinomanometry and symptomatology

The protective effect of sodium cromoglycate (DSCG) on the allergic reaction in the nose was compared with placebo in a double blind crossover study of sixteen patients diagnosed as allergic rhinitis. The drug effect was assessed by both a rhinomanometric method and by symptom scores in all patients. DSCG protected the nasal mucosa against antigen challenge and was significantly better than placebo. There was a correlation between the objective and subjective assessments.     

Local disodium cromoglycate is ineffective in ulcerative proctosigmoiditis

Conflicting results have emerged from studies using oral and rectal disodium cromoglycate (DSCG) in inflammatory bowel disease. In the present double-blind study, 43 patients with active ulcerative proctosigmoiditis received either placebo (n = 22) or 600 mg DSCG (n = 21) rectally as enemas for eight weeks. Assessment was made from clinical investigations, endoscopy, laboratory tests, biopsies, and diary cards. No statistically significant differences in bowel frequency, rectal bleeding, general well-being, abdominal pain, and severity and extent of the disease were found between the groups during the study. There was no significant change in the histologic parameters. No side-effect was encountered. It is concluded that DSCG did not improve symptoms or inflammatory changes in ulcerative proctosigmoiditis.     

Safety and tolerability of fexofenadine for the treatment of allergic rhinitis in children 2 to 5 years old.

BACKGROUND: The safety of fexofenadine has been examined extensively in adults and school-age children. However, the safety of fexofenadine in children younger than 6 years has not been reported to date. OBJECTIVE: To compare the safety and tolerability of twice-daily fexofenadine hydrochloride, 30 mg, and placebo in preschool children aged 2 to 5 years with allergic rhinitis. METHODS: This was a multicenter, double-blind, randomized, placebo-controlled, parallel-group study, conducted between February 29, 2000, and June 14, 2001. Participants were randomized to either fexofenadine hydrochloride, 30 mg, or placebo twice daily for a 2-week period. To facilitate dosing, capsule content was mixed with applesauce (approximately 10 mL). Safety assessments depended on date of entry into the study because of an amendment to the protocol. Before the amendment, assessments included physical examination, vital signs reporting (oral temperature, heart rate, and respiratory rate), and adverse event (AE) reporting. After the amendment, safety assessments included laboratory testing (blood chemistry and hematology profiles), physical examination, 12-lead electrocardiography, and vital signs (oral temperature, blood pressure, heart rate, and respiratory rate) and AE reporting. RESULTS: Treatment-emergent AEs were observed in 116 of 231 participants receiving placebo and 111 of 222 receiving fexofenadine. These AEs were possibly related to study medication in 19 (8.2%) and 21 (9.5%) of the participants receiving placebo and fexofenadine, respectively, and most frequently involved the digestive system. No clinically relevant differences in laboratory measures, vital signs, and physical examinations were observed. CONCLUSIONS: The findings show that fexofenadine hydrochloride, 30 mg, is well tolerated and has a good safety profile in children aged 2 to 5 years with allergic rhinitis.     

Oral Sodium Cromoglycate Treatment of Atopic Dermatitis Related to Food Allergy

Thirty-two children and two adults with chronic atopic dermatitis related to food allergy entered this double-blind crossover study comparing oral sodium cromoglycate (200–1600 mg/24 h) with placebo. Each treatment period comprised 6 weeks: 1 weeks on elimination diet, and 2 weeks on a normal. i.e. unrestricted diet. The diagnosis of food allergy was made after clinical improvement with elimination diet and relapse after challenge. Overall analysis of skin symptoms evaluated by means of clinical assessments and diary cards, opinions of treatment, and use of concomitant medication gave no evidence of any difference between sodium cromoglycate and placebo. Unusual symptoms were reported by 18 patients. In one case the patient was withdrawn during the sodium cromoglycate period because of side effects. The majority of symptoms with both treatments were stomach problems. Overall analysis of the laboratory data gave no significant differences between treatments.     

Randomized, double-blind, placebo-controlled study of montelukast for treating perennial allergic rhinitis.

BACKGROUND: Perennial allergic rhinitis (PAR) is a persistent allergic inflammation of the upper respiratory tract due to year-round allergen exposure. OBJECTIVE: To evaluate the leukotriene receptor antagonist montelukast for the treatment of PAR. METHODS: Protocol 265 was a 2-arm study performed during the winter. After a placebo run-in period, adults with perennial allergen sensitivity and active symptoms of PAR were randomized to receive 10 mg of montelukast (n=1002) or placebo (n=990) once daily during a 6-week, double-blind, active-treatment period. The primary end point was the daytime nasal symptoms score, defined as the average of scores for nasal congestion, rhinorrhea, and sneezing rated daily by patients. RESULTS: Statistically significant improvements in PAR symptoms were seen in patients treated with montelukast. Their daytime nasal symptoms scores were reduced during treatment compared with those of the placebo group: the difference between treatments in least squares mean change from baseline was -0.08 (95% confidence interval [CI], -0.12 to -0.04; P < .001). Montelukast treatment also improved global evaluations of allergic rhinitis by patients and Rhinoconjunctivitis Quality of Life Questionnaire scores: differences vs the placebo group were -0.15 (95% CI, -0.27 to -0.04; P < .01) and -0.15 (95% CI, -0.24 to -0.06; P < .001), respectively. Other end points that showed statistically significant improvement with montelukast treatment were nighttime symptoms and each of the 4 nasal symptoms (congestion, rhinorrhea, sneezing, and itching). The treatment effects of montelukast were stable and persistent during the entire 6 weeks of treatment. CONCLUSION: Montelukast provided statistically significant relief of PAR symptoms during 6 weeks of treatment.     

Disodium cromoglycate: laboratory studies and clinical trial in allergic rhinitis

The ability of disodium cromoglycate (DSCG) to block allergic responses in the nasal airways was investigated in two ways. The effect of DSCG on antigen-induced airways resistance changes in sensitive subjects was investigated in the laboratory. DSCG in a dose of 10 mg applied to each nostril was shown to block the expected reaction in 71 % of subjects and a 1 mg dose in 47%. Protection was conferred against antigen challenge for a period of about 6 hr by the 10 mg dose. A clinical trial of DSCG (10 mg) in seasonal allergic rhinitis was carried out using a double-blind cross-over design. Analysis of the results showed significant DSCG protective effects against lower respiratory tract symptoms and a significant antihistamine sparing effect. Analysis of part of the trial period when antigen challenge was uniformly high showed significant DSCG protective effects against sneezing, nasal discharge and nasal obstruction. Nasal application of DSCG is considered to be a promising alternative therapeutic approach in allergic rhinitis.     

Treatment of Seasonal Allergic Rhinitis with Budesonide and Disodium Cromoglycate

The aim of this study was to compare the efficacy and side effects of budesonide and disodium cromoglycate (DSCG) in seasonal allergic rhinitis. In a double-blind, double-dummy comparative study, 43 patients with seasonal allergic rhinitis were either treated with budesonide (200 micrograms b.d.) or DSCG (5.2 mg 5 times daily). After a 1 week run-in period treatment was given for 3 weeks. The patient scorings for nasal secretion, nasal itching, sneezing bouts and total nasal symptoms were significantly different between the treatment groups during the whole treatment period. The scorings for nasal blockage were significantly different during the last 2 weeks of treatment. All differences were in favour of budesonide treatment. The patients' assessment of the treatment favoured budesonide (P less than 0.02). Side effects were few and mild, but one patient from the budesonide group stopped treatment because of headache.     

Effect of montelukast on symptoms and exhaled nitric oxide levels in 7- to 14-year-old children with seasonal allergic rhinitis.

BACKGROUND: Cysteinyl leukotrienes have been found to exert potent inflammatory effects in the upper airways and play a fundamental role in the pathogenesis of allergic rhinitis. Previous studies have reported increased levels of exhaled nitric oxide (eNO) in patients with allergic rhinitis without asthma symptoms. OBJECTIVE: To investigate the role of treatment with montelukast on symptoms, eNO levels, and peripheral eosinophil counts of children with seasonal allergic rhinitis during pollen season. METHODS: A randomized, double-blind, parallel-group study performed between April and June 2005 in 57 children aged 7 to 14 years with seasonal allergic rhinitis was performed. The study comprised a 1-week screening period, a 1-week run-in period, and a 2-week treatment period with once daily montelukast, 5 mg, or matching placebo. RESULTS: No significant difference at baseline was found in symptom scores, eNO levels, and blood eosinophil counts between the treatment and placebo groups. After 2 weeks of montelukast treatment, improvements from the baseline in the daytime nasal, composite, and daytime eye symptoms scores were significantly greater in the montelukast group compared with the placebo group (P < .001, P < .001, and P < .01, respectively). A significant decrease was also found in eosinophil counts (P < .001) in the montelukast group compared with the placebo group after treatment. Montelukast treatment did not produce a significant effect on eNO levels compared with placebo (P = .96). CONCLUSION: Montelukast treatment provided significant improvement in symptoms and peripheral eosinophil counts of school-age children with seasonal allergic rhinitis; however, it did not show a significant effect on eNO levels.     

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.     

Allergic rhinitis in children: effects of flunisolide and disodium cromoglycate on nasal eosinophil cationic protein

Background Eosinophil cationic protein (ECP) is one of the major, cytotoxic molecules produced by eosinophils, which can be used as a marker of allergic inflammation. Objective In this placebo-controlled study we measured nasal and serum ECP levels to verify their possible role in monitoring the efficacy of anti-inflammatory therapy in allergic chronic rhinitis in 38 children aged from 4 to 14 yr, allergic to house dust mites. Method Nasal ECP, by the method of direct incubation on nasal mucosa, and serum ECP were determined before and after 3 weeks of treatment with flunisolide nasal spray 50 μg twice/daily (13 cases, Group 1), disodium cromoglycate (DSCG) 10.4mg three times/day (15 cases, Group 2) and placebo (10 cases, Group 3). The effectiveness of therapy was evaluated clinically and correlated to serum and nasal ECP values. Results Before treatment no significant difference emerged in the clinical scores of the three groups of patients. Before and after treatment serum ECP levels were not statistically different from normal controls. Before treatment nasal ECP was significantly higher in all patients compared with controls (P < 0.001). Nasal ECP decreased significantly in flunisolide-treated patients (P < 0.01) (before therapy: median 111 μg/L, range from 33.6 to 200 μg/L; after therapy: median 36.8 μg/L, range from 2.6 to 196 μg/D, but not in DSCG-treated patients, (before therapy: median 66.2 μg/L, range from 32.3 to 200 μg/L; after therapy: median 60.4 μg/L, range from 7.9 to l44 μg/L). No significant variation was present in the placebo group. Clinical improvement was statistically significant after flunisolide therapy (P < 0.05), less evident after DSCG (P = 0.06). Conclusion Serum ECP in chronic allergic rhinitis has been shown to be not useful in monitoring allergic inflammation, but nasal ECP, determined by mucosal incubation, may be used to evaluate the activity of eosinophils and monitor the anti-inflammatory efficacy of therapy in chronic rhinitis.     

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.     

Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged ≥ 6 years

OBJECTIVE: Montelukast is a leukotriene receptor antagonist administered orally once daily for treatment of chronic asthma in adults and children. A comprehensive analysis of safety data from double-blind, randomized, placebo-controlled trials with montelukast has not been previously reported. PATIENTS AND METHODS: A pooled analysis of safety data from 11 multicentre, randomized, controlled montelukast Phase IIb and III trials and five long-term extension studies was performed. A total of 3386 adult patients (aged 15-85 years) and 336 paediatric patients (aged 6-14 years) were enrolled in the trials; 2031 adults received montelukast for up to 4.1 years, and 257 children received montelukast for up to 1.8 years. Summary statistics comparing incidences of adverse events among treatment groups were calculated. RESULTS: The overall incidence of clinical and laboratory adverse events among montelukast-treated patients, both adult and paediatric, was similar to that among patients receiving placebo. There were no clinically relevant differences in individual adverse events, including infectious upper respiratory conditions and transaminase elevations, between montelukast and placebo groups. Discontinuations due to adverse events occurred with similar frequencies during placebo, montelukast and inhaled beclomethasone therapy. No dose-related adverse effects of montelukast were observed in adults treated with dosages as high as 200 mg per day (20 times the recommended dose) for 5 months. This tolerability profile montelukast observed in clinical trials has been generally reflected in the post-marketing safety experience seen to date. CONCLUSIONS: These data indicate a tolerability profile for montelukast similar to placebo during both short-term and long-term administration, even at doses substantially higher than the recommended clinical dose of 10 mg once daily for adults and 5 mg once daily for children aged 6-14 years.     

Safety of fexofenadine in children treated for seasonal allergic rhinitis.

BACKGROUND: The incidence of allergic rhinitis in children is increasing. OBJECTIVE: To evaluate the safety of fexofenadine HCI in children ages 6 through 11 years for treatment of seasonal allergic rhinitis. METHODS: Two large, double-blind, randomized, placebo-controlled, parallel studies with identical protocols included patients with a positive skin test to fall allergen(s) and allergic rhinitis symptoms. Patients were randomized to receive fexofenadine 15, 30, or 60 mg or placebo twice daily for 2 weeks after a 1-week placebo lead-in. Safety was evaluated through adverse event reporting, electrocardiograms, and pre- and posttreatment laboratory panels and physical examinations. RESULTS: A total of 875 patients from both studies were eligible for safety analyses. Ten patients (5 on placebo, 5 on fexofenadine) discontinued because of an adverse event; no event that resulted in discontinuation was judged to be caused by study medication. Incidence of adverse events was similar in active and placebo groups, and did not increase with increasing fexofenadine dose: 36.2% (83 of 229) in the placebo group versus 35.3% (79 of 224), 36.8% (77 of 209), and 34.7% (74 of 213) in the 15, 30, and 60 mg twice-daily fexofenadine groups, respectively. Headache was the most commonly reported adverse event (6.6%, 8.0%, 7.2%, and 9.4% in the placebo, 15, 30, 60 mg twice-daily fexofenadine groups, respectively). Clinical, vital sign, electrocardiogram, and laboratory measures were similar in active and placebo groups. There was no statistically significant mean change from baseline in any electrocardiogram parameter after fexofenadine treatment. CONCLUSIONS: Fexofenadine, 15, 30, and 60 mg twice daily, was safe and well tolerated in this large pediatric patient population.     

Multicenter, crossover study of the efficacy and tolerability of terfenadine, 120 mg, versus cetirizine, 10 mg, in perennial allergic rhinitis.

In this 3-week randomized, double-blind, double-dummy multicenter, crossover study terfenadine, 120 mg, was compared with cetirizine, 10 mg, both given once daily in the treatment of perennial allergic rhinitis in sixty patients. Compared with the investigators' pretreatment assessment, both terfenadine and cetirizine significantly reduced the severity of all five symptoms (P less than .001). The two treatments were equally effective in controlling eye irritation, sneezing, nasal congestion and itchy nose, throat and palate, but cetirizine improved rhinorrhea more than terfenadine (P less than .05). Daily symptom assessments by the patients for the last 14 days of each treatment period showed no difference in efficacy between the two drugs for any of the symptoms. There were also no differences between the two drugs for overall assessments of efficacy or patient preference. Adverse events were recorded more frequently while taking cetirizine, with 14 attributable events compared with only five with terfenadine. Four of the cetirizine-related events were drowsiness or tiredness, but none was reported while patients were taking terfenadine. There was a tendency to increased weight (greater than 1 kg) with both treatments.     

Protective effect of disodium cromoglycate against airway constriction induced by hemp dust extract

The effect of disodium cromoglycate (DSCG) was studied in 14 healthy subjects following hemp dust extract (HDE) inhalation (10-min exposure). Ten subjects were given 20 mg of DSCG or a placebo and then challenged with dust aerosol at 30 min post-DSCG inhalation. Partial expiratory flow-volume (PEFV) curves were recorded at least 30 min after exposure, and maximum expiratory flow rates at 40% of the control vital capacity [MEF40%(P)] were read from these curves. Significant acute reductions in MEF40%(P) were recorded after HDE alone and after pretreatment with placebo (p < 0.01). There was considerable protection from a single dose of 20 mg of DSCG against hemp-induced bronchoconstriction although the acute reductions in MEF40%(P) were still statistically significant at 20 and 30 min postexposure. A group of 7 subjects was given 40 mg of DSCG or placebo 30 min prior to HDE inhalation. In another experiment this group was given 20 mg of DSCG four times daily for 2 days, and on the third day challenged with HDE. The protective effect of DSCG is a short-term one: somewhat less protection was seen after 2 days of four times 20 mg of DSCG/day than 30 min after a single dose of 40 mg. Measurement of airway conductance (Gaw) in 6 subjects demonstrated prevention of acute reductions in Gaw at low lung volumes (25% VC) in 4 out of 6 subjects. We suggest that inhalation of 40 mg of DSCG prior to a work shift might be considered as a temporary means of protecting textile workers against the constrictor effects of dust in their work.