{'fraction_non_alphanumeric': 0.03870436453472413, 'fraction_numerical': 0.024704913532802634, 'mean_word_length': 5.359511343804537, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Assessing the therapeutic benefits of antihistamines for the treatment of chronic idiopathic urticaria – a requirement for well‐designed comparative clinical studies

Handa and colleagues (1) recently assessed the comparative efficacy of fexofenadine HCI 180 mg and cetirizine 10 mg once daily (q.d.) in 97 patients with chronic idiopathic urticaria (CIU), and generated somewhat surprising results. The study highlighted that cetirizine had a therapeutic advantage over fexofenadine in the treatment of CIU. As this is the first published comparative clinical trial of cetirizine and fexofenadine in this disorder, the results should be interpreted with caution before implementing the authors’ conclusion in the daily management of CIU. At the end of the 28-day study period, 51.9% (27/ 52) and 4.5% (2/45) of cetirizineand fexofenadinetreated patients, respectively, were symptom-free (p50.00001). However, the authors failed to provide baseline symptom severity data scores for either treatment group or discuss how patients’ symptoms were assessed. More importantly, the variability of this outcome measure appears to be wide. In another CIU study, 30% and 11% of cetirizine(10 mg q.d.) and placebo-treated patients were reported as being symptom-free (2). If we consider a ratio of 1.73 between these two studies (1,2) for the cetirizine arm, a hypothetical placebo arm in the Handa study (1) would have reported approximately 19% of symptom-free patients. This would suggest that the percentage of symptom-free patients receiving fexofenadine would hypothetically be lower than that estimated for placebo. We, therefore, doubt the reliability and robustness of this outcome measure and challenge the authors’ conclusions. In most published trials in CIU, mean daily changes from baseline in pruritus severity and number of wheals are normally assessed as study endpoints (2–5). Fexofenadine HCl 180 mg q.d. has shown significant improvements in the pruritus score and reductions in the number of wheals compared with placebo (pv0.05) over a 6-week study period in adults with CIU (5). Similarly, in additional studies, fexofenadine HCI 60, 120 and 240 mg twice daily doses effectively relieved pruritus severity and decreased the number of wheals in CIU patients (3,4). Importantly, in the absence of well-designed comparative clinical trials, the published placebo-controlled data provide reassurance that fexofenadine and cetirizine are both effective for the treatment of CIU (2–5), but they do not allow the physician to differentiate clearly between them. When considering antihistamines as a potential treatment option for CIU, the appropriate agent should achieve optimal effectiveness with the most acceptable side effect profile. Interestingly, in this study (1) adverse effects occurred more frequently with cetirizine than fexofenadine: 7.7% (4/52) and 4.5% (2/45) of cetirizineand fexofenadine-treated patients, respectively, experienced drowsiness. It has previously been shown that cetirizine may produce more drowsiness and impairment than other newergeneration antihistamines (6). In addition, 23.7% (23/116) of patients enrolled in this study (1) had constitutional symptoms including fever, arthralgia and abdominal pain, which is in contrast to other published studies (2–5), suggesting that this may have influenced the study outcome measure. To conclude, we urge caution in the interpretation of this study (1) and recommend that comparative clinical trials for CIU be performed using reliable and reproducible measures, with full disclosure of the study design that will safeguard against questionable conclusions.