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Urticaria, and especially chronic spontaneous urticaria (CSU), is a difficult condition to treat. Consequently, clinicians need to use the best H(1)-antihistamines currently available and the pharmaceutical industries need to keep developing H(1)-antihistamines that are more effective than the ones we have today. To do this we need to be able to compare the clinical efficacy of both established and new drugs. Obviously, the ideal way to do this is to use head-to-head studies in CSU. However, such studies are extremely expensive and, in the case of novel molecules, have ethical and logistical problems. Consequently, we need to have predictive models. Although determination of Ki, an indicator of the in vitro potency of an H(1)-antihistamine, may help in the initial selection of candidate molecules, the large differences in volume of distribution and tissue accumulation in humans, precludes this from being a good predictor of clinical efficacy in CSU. From the data reviewed in this article, especially the direct comparative data of desloratadine and levocetirizine in weal and flare studies and CSU, weal and flare response would appear to be the best indicator we have of effectiveness of H(1)-antihistamines in clinical practice. However, it must be pointed out that the conclusion is, essentially, based on detailed comparisons of two drugs in studies sponsored by pharmaceutical companies. Consequently, to confirm the conclusions of this review, a multicentre study independent from the influence of pharmaceutical companies should be commissioned to compare the speed of onset and effectiveness of desloratadine, fexofenadine and levocetirizine in chronic spontaneous urticaria and against histamine-induced weal and flare responses in the same patients so that we have a clear understanding of the predictive value of our models., (© 2012 Blackwell Publishing Ltd.)

Summary Background There are no data directly comparing the relative efficacy of modern H(1)-antihistamines in allergic rhinitis using nasal provocation challenge. Objective We elected to study the comparative effectiveness of usual clinically recommended doses of desloratadine (DES), fexofenadine (FEX), and levocetirizine (LEV), on nasal adenosine monophosphate (AMP) challenge in patients with perennial allergic rhinitis (PAR). Methods 16 patients with PAR were randomized in double-blind cross-over fashion to receive single doses of DES 5 mg, FEX 180 mg, LEV 5 mg, or placebo (PL), with nasal AMP challenge performed 12 h after dosing. Measurements of peak nasal inspiratory flow (PNIF) were made over 60 min after nasal AMP challenge. Results Pre-challenge values (mean+/-SEM) for PNIF (L/min) were not significantly different comparing all groups; DES (129+/-9), FEX (128+/-11), LEV (128+/-13), and PL (128+/-12). The maximum % PNIF fall from baseline over 60 min after nasal AMP challenge was significantly attenuated (P<0.05) compared to PL (50+/-4), with DES (32+/-5), FEX (36+/-4), and LEV (36+/-4). The area under the 60-min time-response curve (%.min) was also significantly attenuated (P<0.05) compared to PL (2110+/-268), with DES (1126+/-285), FEX (1225+/-255), and LEV (1261+/-194). There were no significant differences between the three H(1)-antihistamines for any outcomes. Conclusion DES, FEX, and LEV were equally effective in attenuating the response to nasal AMP challenge. However, further long-term studies will be required to study their comparative effects on nasal symptoms, quality of life, as well as on nasal inflammatory cells.

Background: There are presently no placebo-controlled data regarding the effects of butterbur (BB) on subjective and objective outcomes in patients with perennial allergic rhinitis., Objective: We performed a placebo-controlled evaluation of the effects of BB and fexofenadine (FEX) on subjective and objective outcomes in patients with perennial allergic rhinitis., Methods: Sixteen patients with perennial allergic rhinitis and house dust mite sensitization were randomized in double-blind cross-over fashion to receive for 1 week either BB 50 mg twice daily, FEX 180 mg once daily and placebo (PL) once daily, or PL twice daily. The peak nasal inspiratory flow (PNIF) response to adenosine monophosphate (AMP) challenge administered as a single 400 mg/mL dose was measured over a 60-min period after challenge, and domiciliary total nasal symptom score was recorded., Results: Pre-challenge values for mean+/-SEM PNIF (L/min) were not significantly different comparing all groups; BB (138+/-8), FEX (140+/-9), and PL (138+/-8). The maximum % PNIF fall from baseline after nasal AMP challenge was significantly attenuated (P<0.05) compared to PL (46+/-3), with BB (34+/-3) and FEX (39+/-3). The area under the 60-min time-response curve (%.min) was also significantly attenuated (P<0.05) compared to PL (1734+/-156), with BB (1052+/-258) and FEX (1194+/-161). There was also a significant reduction (P<0.05) in total nasal symptom score with BB (1.8+/-0.4) and FEX (1.8+/-0.4), compared to PL (2.8+/-0.5). There were no significant differences between BB and FEX for any outcomes., Conclusion: BB and FEX, in comparison to PL, were equally effective in attenuating the nasal response to AMP and in improving nasal symptoms, highlighting a potential role for BB in the treatment of allergic rhinitis.

Background: In vitro studies have shown much higher H1-receptor antagonist potency with desloratadine (DL) compared to fexofenadine (FEX), although it is unclear whether this has any clinical relevance on disease control parameters in seasonal allergic rhinitis (SAR), especially for nasal congestion., Objective: To compare the relative efficacy between presently recommended doses of DL and FEX on daily measurements of peak nasal inspiratory flow (PNIF) and nasal symptoms in SAR., Methods: Forty-nine patients with SAR were randomized into a double-blind, placebo-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 180 mg FEX or (b) 5 mg DL, taken in the morning. There was a 7-10 day placebo run-in and washout prior to each randomized treatment. Measurements were made in the morning (AM) and in the evening (PM) for PNIF (the primary outcome variable), nasal and eye symptoms. The average of AM/PM values were used for analysis., Results: There were significant (P < 0.05) improvements, compared to placebo, with FEX and DL, for PNIF, nasal blockage, nasal irritation, and total nasal symptoms, but not nasal discharge or eye symptoms. There were no significant differences between active treatments. Values for PNIF (L/min) for mean placebo baseline, mean difference from baseline (95% CI for difference) were 126, 10 (4-16) for FEX; and 122, 11 (4-17) for DL. The mean difference (95% CI) between FEX vs. DL was 1 L/min (-7-8). Values for total nasal symptoms (out of 12) were: 3.2, 0.7 (0.2-1.2) for FEX; and 3.4, 0.9 (0.3-1.5) for DL, and for nasal blockage (out of 3) were: 1.1, 0.2 (0.1-0.4) for FEX; and 1.2, 0.3 (0.1-0.5) for DL. The mean difference (95% CI) in total nasal symptoms and nasal blockage between FEX vs. DL was 0.1 (-0.6-0.8) and 0.1 (-0.2-0.3), respectively., Conclusions: Recommended once daily doses of fexofenadine and desloratadine were equally effective in improving nasal peak flow and nasal symptoms in SAR.

Background: The combination of montelukast (ML) and loratadine (LT) has previously been shown to be superior to either drug alone in managing seasonal allergic rhinitis (SAR), whilst fexofenadine (FEX) has been shown to be better than LT as monotherapy., Objectives: We wished to compare ML + LT vs. FEX alone for effects on daily measurements (am/pm) of peak inspiratory flow (PIF) and symptoms., Methods: Thirty-seven patients with SAR (skin prick positive to grass pollen) were randomised into a single-blind, double-dummy placebo (PL)-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 120mg FEX or (b) 10mg ML + 10mg LT. There was a 7-10 day placebo run-in and washout prior to each randomised treatment. The average of am/pm PIF (the primary outcome variable) was analysed. Patients recorded their symptom scores (from 0 to 3) twice daily, for nasal blockage, discharge, itching and sneezing with; total eye symptoms, ocular cromoglycate use, and daily activity. The total nasal symptom score was calculated as a composite (out of 24)., Results: There were no significant differences between baselines after the run-in and washout placebos for any variables. There were significant (P < 0.05, Bonferroni) improvements in all symptoms and PIF compared to pooled placebo with both treatments for all end-points, but no differences between the two treatment regimes (as means and within-treatment 95% confidence intervals): PIF: PL 102 (98-107), FEX 111 (107-116), ML+LT 113 (109-118); total nasal symptoms: PL 7.4 (6.7-2.0), FEX 5.0 (4.3-5.7), ML + LT 4.0 (3.3-4.7)., Conclusions: Once daily FEX as monotherapy was equally effective as the combination of once daily ML + LT in improving nasal peak flow and controlling symptoms in SAR. Further studies are indicated to assess whether ML confers additional benefits to FEX in SAR.

Background: As there have been no previously published studies, this multinational, double-blind, randomized, placebo-controlled, parallel group study compared the efficacy, safety and impact on quality of life (QoL) in seasonal allergic rhinitis patients (SAR) of fexofenadine and loratadine (with placebo), when administered once daily., Methods: Six hundred and eighty-eight SAR patients were randomized to receive fexofenadine HCl 120 mg, loratadine 10 mg or placebo, once daily for 2 weeks. The key parameters were the change from baseline in: mean 24-h reflective total symptom scores (TSS); sum of four individual symptom scores, excluding nasal congestion; instantaneous TSS; individual symptom scores including nasal congestion; and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Adverse events were recorded., Results: Mean 24-h reflective and instantaneous TSS were significantly reduced by both fexofenadine HCl (both P

Fluticasone Propionate Aqueous Nasal Spray (FPANS) contains a topically active glucocorticoid fluticasone propionate which has been used successfully for the treatment of seasonal allergic rhinitis. This multicentre, randomized, double-blind, double-dummy, placebo-controlled, parallel group study was designed to compare the efficacy and tolerability of FPANS with terfenadine tablets or placebo in controlling the symptoms of allergic rhinitis to grass pollen. Two hundred and fourteen patients were treated for 6 weeks during the grass pollen season with either FPANS 200 micrograms once daily, terfenadine tablets (60 mg) twice daily or placebo. Efficacy was evaluated by the analysis of symptom-free days and median symptom scores. Patients receiving FPANS had significantly more days free of nasal blockage on waking (P = 0.012) and during the day (P = 0.01) and of rhinorrhoea (P = 0.027) than those receiving terfenadine. Additionally, in terms of absolute efficacy, patients receiving FPANS demonstrated significantly more days free of the above symptoms (P = 0.017, P = 0.028, P = 0.004, respectively) and of sneezing (P < 0.001) than those receiving placebo. There were no significant differences in symptoms of nasal itching, eye symptoms, of symptoms of drowsiness between the three treatment groups. Patients in the FPANS group had significantly lower median symptom scores for nasal blockage on waking (P < 0.001) and during the day (P < 0.018) than those in the terfenadine group and significantly lower scores for nasal blockage on waking (P < 0.001), sneezing (P < 0.013) and rhinorrhoea (P = 0.005) than those in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of three oral doses of a new compound KW 4679 thought to have both antihistaminic and antiallergic properties were compared with terfenadine and placebo in a double-blind cross-over trial in 15 volunteers with seasonal allergic rhinitis. Comparison of the effect of the treatments with either 2.5, 5 or 10 mg b.i.d. of KW 4679, 60 mg b.i.d. of terfenadine or placebo was made on the response to histamine and grass pollen skin-prick testing. Nasal provocation testing with grass pollen was performed on the eighth day of treatment. Nasal airway resistance (NAR) was measured using active posterior rhinomanometry and the dose of grass pollen which caused a 200% increase in NAR was determined. The number of sneezes in the first 12 min was counted. Compared with placebo all doses of KW 4679 and terfenadine significantly inhibited the skin weal response to histamine and grass pollen (P < 0.001). The inhibitory effect of KW 4679 on both histamine and allergen induced skin weals was significantly greater than that of terfenadine (P = 0.001 and P = 0.049 respectively). The results of nasal challenges with grass pollen showed that all doses of KW 4679 and terfenadine were effective in reducing sneeze counts (P < 0.001), though there were no significant effects on allergen induced increase in NAR. All three doses of KW 4679 were generally well tolerated. Drowsiness was reported by some of the volunteers on KW 4679 and one volunteer reported drowsiness whilst taking placebo. Slight and reversible rises in AST and ALT concentrations were observed; these were not considered clinically significant.

Nasal instillation of bradykinin elicits many of the characteristic features of rhinitis. To assess the relevance of histamine release from metachromatic cells and the activation of cholinergic pathways, we investigated the effects of terfenadine, a histamine H1-receptor antagonist, and ipratroprium bromide, a selective antimuscarinic agent, on bradykinin induced rhinorrhoea, nasal airways resistance (NAR), nasal pain and plasma protein leakage. Oral terfenadine (120 mg) or matched placebo and nasal ipratropium bromide (80 micrograms) or matched placebo were administered at 4 hr and 30 min respectively prior to bradykinin nasal challenge in two randomized, double-blind and cross-over studies on eight non-rhinitic subjects. Thus subjects received either double-placebo, oral terfenadine and nasal placebo, oral placebo and nasal ipratopium bromide or oral terfenadine and nasal ipratropium bromide, as pretreatment. Bradykinin challenge induced mean maximal increases of 57%, 59%, 77% and 72% in NAR on the placebo, terfenadine, ipratropium bromide and terfenadine plus ipratropium bromide pretreatment days respectively. These increments were not significantly different. Similarly rhinorrhoea and nasal pain induced by bradykinin nasal challenge were not significantly different on the four challenge days. Bradykinin nasal challenge caused a mean maximal increase in albumin levels in recovered nasal lavages of 11.5, 13.0, 12.2 and 12.3 times of baseline levels on the placebo, terfenadine, ipratropium bromide and terfenadine plus ipratroprium bromide pretreatment days respectively. Similarly total protein levels achieved a mean maximal increase of 8.0, 8.2, 7.9 and 8.8 times of baseline levels on these challenge days. The increments in both albumin and total protein did not significantly differ on the 4 challenge days.(ABSTRACT TRUNCATED AT 250 WORDS)

In a double-blind placebo-controlled trial on 52 patients with bee venom allergy we studied the effect of a pretreatment with terfenadine 120 mg twice daily on the occurrence of local and systemic allergic side effects from rush-immunotherapy. Large local reactions were significantly reduced by terfenadine pretreatment (P less than 0.01), while systemic side effects were observed with similar frequencies in both groups. Analysis of individual systemic allergic manifestations showed that cutaneous symptoms like itching (P less than 0.025) and urticaria/angioedema (P less than 0.05) were significantly reduced, while respiratory or cardiovascular symptoms were not influenced. A lower consumption of additional anti-allergic medication was found during terfenadine pretreatment (P less than 0.05). Pretreatment with antihistamines during immunotherapy may thus be helpful in the management of patients with cutaneous side effects.