Gary Feiss

A comparison of effects of triamcinolone acetonide aqueous nasal spray, oral prednisone, and placebo on adrenocortical function in male patients with allergic rhinitis☆☆☆★★★

BACKGROUND One of the risks associated with the use of oral corticosteroids is suppression of adrenocortical function. Triamcinolone acetonide (TAA) aqueous nasal spray administered once daily (110 micrograms and 220 micrograms) has been shown to reduce allergic rhinitis symptoms. OBJECTIVE This multicenter, placebo-controlled, double-blind study determined the effects of TAA aqueous nasal spray, placebo, and oral prednisone on adrenocortical function in patients with allergic rhinitis. METHODS Sixty-four patients received TAA aqueous nasal spray (220 micrograms or 440 micrograms), oral prednisone (10 mg), or placebo once daily for 6 weeks. Adrenocortical function was assessed after cosyntropin stimulation for 6 hours before treatment and after 6 weeks of treatment. RESULTS There was no statistically significant effect on adrenocortical function in patients who received either dose of TAA aqueous nasal spray compared with placebo. In contrast, prednisone produced statistically significant (p < 0.001) reductions in adrenocortical function compared with placebo; reductions occurred in both the mean 6-hour plasma cortisol levels and mean change in 6-hour plasma cortisol levels from pretreatment. CONCLUSION This study demonstrated that, unlike oral prednisone, TAA aqueous nasal spray, in therapeutic doses, did not alter adrenocortical function and was comparable to treatment with placebo in its absence of measurable effects on adrenocortical function.

Efficacy and safety of triamcinolone acetonide aqueous nasal spray in patients with seasonal allergic rhinitis

BACKGROUND In order to accommodate increasing patient preferences a new aqueous formulation of triamcinolone acetonide nasal spray was developed for the relief of symptoms associated with seasonal and perennial allergic rhinitis. OBJECTIVE This multicenter, randomized, double-blind study was designed to compare the efficacy and safety of once-daily triamcinolone acetonide aqueous nasal spray (220 micrograms/day) with placebo in relieving the symptoms of seasonal allergic rhinitis due to ragweed. METHODS One hundred forty patients received either a once daily 220-microgram dose of triamcinolone acetonide aqueous nasal spray or placebo for 2 weeks. Patients evaluated the severity of seasonal allergic rhinitis symptoms daily for 2 weeks according to a 4-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Physician and patient global evaluations of overall treatment effectiveness were assessed at the end of the treatment period. RESULTS Patients receiving triamcinolone acetonide aqueous nasal spray, 220 micrograms/day, had significantly (P < .05) greater improvements in all rhinitis symptoms at weeks 1 and 2 and overall for the 2-week treatment period compared with the placebo group. A significant (P = .006) improvement in the nasal index occurred as early as 12 hours after the first dose of triamcinolone acetonide aqueous nasal spray. Both patients and physicians reported a greater overall improvement in symptoms for the triamcinolone acetonide aqueous nasal spray group. There were no differences between the two treatment groups in the incidence of adverse events. CONCLUSIONS This study confirmed that a 220-microgram dose of triamcinolone acetonide aqueous nasal spray, administered once daily for 2 weeks, is well tolerated and reduces effectively the severity of symptoms of seasonal allergic rhinitis due to ragweed.

A comparative study of the effects of intranasal triamcinolone acetonide aerosol (ITAA) and prednisone on adrenocortical function

A comparison of adrenocortical function before and after treatment with either intranasal triamcinolone acetonide aerosol (ITAA), prednisone, or placebo was done. Sixty-two male subjects with allergic rhinitis were treated for 6 weeks with either ITAA (220 or 440 micrograms/day), oral prednisone (10 mg/day), or placebo in double-blind, parallel-group fashion. Adrenocortical function was assessed by 6-hour cosyntropin stimulation before and at the end of the treatment period. The placebo-treated and two ITAA-treated groups produced no changes in adrenocortical function with treatment, and the ITAA-treated groups were not different from the placebo-treated group with mean +/- SEM changes in stimulated plasma cortisol (micrograms per deciliter) as follows: placebo, -2.68 +/- 1.77; ITAA 220 micrograms, -2.69 +/- 1.18; ITAA 440 micrograms, -2.96 +/- 1.81. The prednisone-treated group had a mean reduction in adrenocortical function (mean +/- SEM change in stimulated plasma cortisol of -19.8 +/- 1.77 micrograms/dl) that was significant (p less than 0.0001) compared with that of the placebo-treated group. The results of this study indicate that 6 weeks of treatment with 220 micrograms/day or 440 micrograms/day of ITAA has no effect on adrenocortical function, but prednisone, at a dosage of 10 mg/day for 6 weeks, produces partial adrenocortical suppression.

Long-term safety and efficacy of triamcinolone acetonide aqueous nasal spray for the treatment of perennial allergic rhinitis.

This 12-month, multicenter, open-label study to assess the long-term safety and efficacy of triamcinolone acetonide (TAA) aqueous nasal spray for perennial allergic rhinitis (PAR) symptom relief was a continuation of a 4-week, double-blind study. Patients who received TAA Aqueous (220 micrograms/day) during the 4-week, double-blind study continued with the same treatment for the open label study; those randomized to placebo during the 4-week, double-blind study received TAA Aqueous (220 micrograms/day) for the open-label study. Dose reduction to 110 micrograms/day was allowed if it was felt that symptom relief would be maintained. Safety was assessed by daily diary entries and clinical laboratory results. Long-term efficacy was assessed by visual analog scale (VAS). Of the 172 patients who began the open-label study, 94.2 percent completed 3 months of treatment, 83.6 percent completed 6 months, and 62 percent completed 12 months. PAR symptom relief improved progressively throughout the study. Adverse events were generally mild or moderate and consistent with long-term use and winter symptoms. The most common adverse events were pharyngitis (32 percent of patients), rhinitis (28.5 percent), headache (22.1 percent), and epistaxis (18 percent). Adverse events related to the local effects of the study medication were similar to those observed in long-term studies with TAA aerosol. The aqueous nasal spray formulation of triamcinolone acetonide was well tolerated and continued to relieve nasal symptoms with long-term use in adolescent and adult patients with PAR.

Poster 33: Triamcinolone Acetonide Aqueous Nasal Spray does not Alter Adrenocortical Function in Children with Allergic Rhinitis

used as controls. The characteristics of the glycoprotein and the mitotic activity of the olfactory epithelial cells were investigated using eight kinds of lectins and BrdU (50 mg/ kg), which was injected an hour before sacrifice. The results were as follows: 1. In experimental groups the olfactory epithelium showed degenerative changes such as atrophy and squamous metaplasia, which were observed until 2 weeks after the inhalation. 2. The olfactory epithelium started to recover in 3 weeks and showed a similar state compared with the control group in 4 weeks after the inhalation. 3. In the control group, positive reactions appeared in the supporting cells to PNA, SBA, WGA, ECL, and PHA-L; in the olfactory cells to PNA, SBA, WGA, and UEA; and in the proper basal cells to GS-I, SBA, WGA, and PHA-L. In the experimental groups the positive reaction increased in the supporting cells to SBA, ECL, and PHA-L and in Bowmans gland to all used lectins, except ECL and GS-I. 4. The number of BrdU-labeled cells in the olfactory epithelium was 14.83 _+ 1.21/ram in the control group. The mitotic activities were decreased to 4.8 _+ 0.8/mm in 2 weeks and recovered within 3 weeks after the inhalation. 5. The double-labeling immunostaining method was performed with proper basal cell-specific lectins (GS-I or PHAL) and BrdU to find the stem cells of olfactory receptor cells. In BrdU-labeled cells containing positive reactions to these specific lectins, the proper basal cells occupied 18% in control groups and 60.7% in lesioned groups (4 days to 2 weeks after inhalation) and 44.5% in recovery groups (3 to 6 weeks after inhalation). In conclusion, formaldehyde gas inhalation causes atrophy and squamous metaplastic changes of olfactory epithelium and the proper basal cells take charge of more active mitotic activity in the regeneration of the olfactory epithelium rather than globose basal cells after the cytotoxic damage of formaldehyde gas.