Review of H1 Antihistamines in the Treatment of ... - Ob.Gyn. News

Antihistamines for CIUDesloratadine—Desloratadine is the major activemetabolite of loratadine, which has been availablein the United States since 2002 for the treatment ofCIU. The efficacy of the drug has been evaluated in2 major randomized controlled clinical trials. 37,38Ring et al 37 reported that desloratadine exhibitedsuperior efficacy compared with placebo in amulticenter, randomized, double-blind trial of190 patients with a history of CIU. Patients wereassigned to receive either desloratadine 5 mg QDor placebo QD for 6 weeks. The active treatmentwas superior to placebo at reducing pruritus andoverall symptoms after the first dose and throughoutthe 6-week study. 37 Similarly, therapeuticresponse and global CIU status, as well as QOLmeasures such as interference with sleep, wereimproved with desloratadine compared withplacebo throughout the study period. 37 Using thesame dose (5 mg QD), a further 6-week placebocontrolledstudy of desloratadine indicated theeffectiveness of this agent at relieving CIU symptoms.38 Over the study period, the mean total CIUsymptom score was significantly improved comparedwith placebo, as were the individual scores ofpruritus, number of hives, and the size of the largesthive. Interference with sleep was reduced and performanceof daily activities was improved withdesloratadine. These statistically and clinically significantimprovements were seen within the first24 hours of treatment and were sustained throughoutthe 6-week treatment period. 38Cetirizine—As with loratadine, cetirizine hasbeen shown to be as effective as first-generationhydroxyzine at relieving the symptoms of CIU. 40For example, a 4-week, multicenter, randomized,double-blind, double-dummy trial investigated theefficacy and safety of cetirizine 10 mg QD andhydroxyzine 25 mg 3 times daily compared withplacebo in patients with CIU. Patients in the cetirizineand hydroxyzine groups showed significantreductions during weeks 1, 2, 3, and 4 in the numberand size of lesions and in the severity of prurituscompared with patients who received placebo.In addition, physician and patient evaluations atthe end of week 4 revealed an improvement inurticarial symptoms for the cetirizine and hydroxyzinegroups compared with the placebo group. 40All 4 newer-generation H 1antihistamines (fexofenadine,loratadine, desloratadine, and cetirizine)have been shown to be superior to placebo at treatingthe symptoms of CIU, and both loratadine andcetirizine have been proven to be as effective asfirst-generation hydroxyzine. 35,40 Although no trialshave evaluated fexofenadine and desloratadine comparedwith hydroxyzine, comparisons demonstratingequivalence have been made with their parent compounds(loratadine 35 and terfenadine 45 ).There are few controlled studies in whichnewer-generation antihistamines have been directlycompared, and there is no evidence-based datademonstrating statistical superiority of one secondgenerationagent over another in the treatment ofCIU. For example, although a recent trial comparedthe efficacy of cetirizine with fexofenadine,the results are weakened by the study design.Patients with CIU were randomized to eithercetirizine 10 mg (n52) or fexofenadine 180 mg(n45); at 28 days, 51.9% (27) and 4.4% (2) ofcetirizine and fexofenadine patients, respectively,were symptom free (P.00001), while partialimprovement was experienced by 36.5% (19) ofcetirizine patients and 42.2% (19) of fexofenadinepatients. 46 However, there was no control group,baseline symptom severity data were not provided,and the authors did not describe how thepatients’ symptoms were assessed. 46 Therefore, adefinitive assessment of the relative efficacy ofnewer-generation antihistamines cannot be achievedby reviewing published trials alone.Anti-inflammatory PropertiesDue to the absence of well-designed placebocontrolledcomparisons of newer-generation antihistamines,other properties have been examinedto aid treatment comparisons. For example, it hasbeen suggested that some H 1-receptor antagonistsmay achieve anti-inflammatory effects in a clinicalcontext, which could prove advantageous in thetreatment of CIU because the disease is characterizedby tissue inflammation. 47To investigate the anti-inflammatory activity offexofenadine, an immunohistochemical evaluationof the agent was undertaken in patients with CIU. 48Twenty patients received fexofenadine HCl 180 mgQD for 4 weeks; the expression of adhesionmolecules, mast cell proteases, and proinflammatorycytokines were evaluated before and after treatment,as were the patients’ assessments of urticarial symptoms.After treatment with fexofenadine, significantdecreases in the expression of endothelial leukocyteadhesion molecule-1 (P.02), vascular cell adhesionmolecule-1 (P.04), and tryptase (P.04) wereobserved, confirming the hypothesis that fexofenadinehas some anti-inflammatory properties.This study in humans must be put into contextwith the numerous in vitro, ex vivo, and animalstudies that have been conducted in this area. A reviewof such data suggests that all newer-generationantihistamines inhibit the release or generation ofmultiple inflammatory mediators, including IL-4,122 CUTIS ®