A Comparison of Three Injectable Corticosteroids for the Treatment of Patients with Seasonal Hay Fever

0 Bengt 0 Oblander, Otorhinolaryngology Department, Roy E Hansson and Karl-Erik Karlsson, Clinical Chemistry Department, Central Hospital , S-351 85 Vdxjo , Sweden Three injectable corticosteroids, betamethasone dipropionate,* betamethasone disodium phosphate and betamethasone acetate,** and methylprednisolone acetate,*** were compared for onset and duration of action in patients with severe seasonal allergic rhinoconjunctivitis. The sixty patients who were entered into the trial had been well-studied in our allergy clinic. They were assigned. on the basis ofa random number code. to treatment with one of the corticosteroids. Following a single intramuscular injection with one of the preparations, plasma cortisol and blood glucose concentrations also were compared at days 1, 2-3. 5-7 and 14. All three preparations improved the nasal symptoms. There were no individual differences with respect to onset or to duration of action. However, there were some differences in the effects on endogenous cortisol production and on blood glucose levels. Two of the preparations. betamethasone dipropionate and methylprednisolone acetate, suppressed endogenous cortisol for more than 14 days, while betamethasone phosphate/acetate did not suppress cortisol beyond 12 days. Betamethasone dipropionate produced a moderate increase in blood glucose concentrations for the first two days after administration; betamethasone phosphate/acetate caused an increase for one day and methylprednisolone acetate had no effect. - Patients with seasonal hay fever, that may be very debilitating during the pollen season, are very common in an otolaryngological practice. For almost three decades, corticosteroids have been among the most effective treatments available for such patients. And during the past ten years, intranasal administration of cromoglycate and the corticosteroid, beclo methasone dipropionate, have served as alternative measures to systemic therapy of *Diprosone **Celestona Bifas ***Depomedrone allergic and vasomotor rhinitis (Lofkvist & Svensson 1975). However, local adminis tration does not replace systemic therapy entirely, especially for patients who are very severely affected by their condition. While new derivatives of cortisone and cortisol are being introduced continuously, the effects and side-effects of these new compounds are, for the most part, following the well-established patterns of the early substances (Axelsson & Lindholm 1972). Nevertheless, there is a need for controlled studies to compare the actions and side-effects of new corticosteroid compounds. Cambridge Medical Publications Limited Therefore, we undertook to compare the onset and duration of action of three long acting corticosteroid compounds: betamethasone dipropionate,* 5 mg; beta methasone disodium phosphate, 3 mg, and betamethasone acetate, ** 3 mg; and methyl prednisolone acetate,*** 40 mg; in patients with seasonal allergic rhinitis with or without conjunctivitis. We also planned to evaluate changes in plasma cortisol levels and blood glucose concentrations. Materials and Definitions We entered into the trial sixty patients who had severe hay fever every summer for six to eight weeks. The patients, who were symptom free for the remainder of the year, were allergic to various grass pollens as determined by intradermal and provocating tests. Most of the patients, fifty-one of sixty, had experienced severe symptoms for three years or more; the remainder had been symptomatic at least for the two previous seasons. Consequently, their patterns of response were well-known to us in the allergy unit. Nevertheless, complete physical examinations were carried out before the study was started and the following patient exclusions were made: those who had received any type of corticosteroid therapy during the previous four weeks; those with sinusitis, nasal infections or polyps, herpes simplex or asthma; pregnant women or breast-feeding mothers; those with contraindications to cortiPatient characteristics in the three separate treatment groups costeroid therapy or with a history of hyper sensitivity to other components of the preparations; those requiring other treatment that would require concomitant treatment with agents that might influence the allergic condition. The patients, who agreed not to use anti histamines and/or decongestants during the trial observation period, are described in Table 1. Methods The patients, who were assigned to one of the three treatment groups on a random basis, received an intramuscular injection of 1 ml betamethasone dipropionate, 1 ml of betamethasone disodium phosphate/acetate, or 2 ml methylprednisolone acetate. The therapeutic response was evaluated at one, two, and four weeks after the injection by the same investigator who recorded the patients' evaluations and his own scoring of the symptoms of nasal congestion, running nose, and eye symptoms. Patients were asked to record onset and duration of improvement or a symptom-free state. They also were asked to record the development of any side-effects. Blood samples were taken from the first thirty-eight patients on four or more separate occasions: immediately preceding the injection; during the next three days; after one week, days five to seven; and after two weeks, day fourteen. Since the out-patients were B etamethasone dipropionate Betamethasone disodium phosphate!acetate I I I I I 17 Severity of presenting signs and symptoms in patients in the three separate treatment groups Betamethasone dipropionate Betamethasone disodium phosphate/acetate 2 0 0 0 3 (I) I 12 2 2 0(2) 0 3 0 10 (I) Onset and duration of action of three corticosteroids in patients with seasonal hay fever Betamethasone dipropionate Betamethasone disodium phosphate/acetate Note: Number equals patients who were symptom-free; number in parentheses indicates number of patients who were improved. Only nineteen patients treated with betamethasone dipropionate were evaluated since one patient did not return after the initial visit. working at the time of the study, the blood sampling time had to be modified to each individual's work schedule. Therefore, for each patient, the best time between 8.00 a.m. and 4.00 p.m. was selected and used throughout the investigation. As a result, changes in plasma cortisol or blood glucose, which are subject to the influence of the diurnal rhythm, could be compared only to each individual's pre therapy value and reported as a percentage of that. For statistical evaluation of the prolonged suppressive action of plasma cortisol by the synthetic corticosteroids, the 'area under the curve' (plasma cortisol versus time) technique was used (Gibaldi & Perrier 1975). The c~lculations. were bas~d on the assum~tion of a bi-exponential function C, = 1 + e" It - e-k1t (Wagner & Pernarouski 1971). Variance analysis was used as well to judge for consistent behaviour in the three test groups. For blood glucose levels, analysis of vari (...truncated)