Therapeutic Research

Objective：This drug use‒results survey was conducted to evaluate the safety and effectiveness of fexofenadine, Allegra® 5％ Dry Syrup（ALE DS）, for young children with allergic rhinitis and skin disorders in the real‒world setting of Japanese clinical practice. Methods：This observational study was conducted in accordance with Japan GPSP regulations. In this nationwide prospective product registry, children（aged 6 months to 7 years）who had been prescribed ALE DS were eligible for enrollment. According to the package insert, ALE DS is indicated for the treatment allergic rhinitis, urticaria, or pruritus associated with cutaneous disease（eczema cutaneous pruritus, atopic dermatitis）. Per‒label, children aged 6 months to 2 years and 2 to 7 years are to receive fexofenadine hydrochloride 15 mg（as 0.3 g ALE DS）and 30 mg（as 0.6 g ALE DS）twice daily, respectively. Safety was assessed through the occurrence of adverse events（AE, evaluated in number of patient‒cases and events）, adverse drug reaction（ADR）, their severity and outcomes. In particular, the incidence of predefined neurological adverse events was assessed as an outcome of particular interest. Subgroup analyses based on body weight and age（under 2 years）were also conducted. The primary endpoint for effectiveness was the physician‒rated global improvement scale（GIS）at 4‒week treatment after ALE DS initiation and at the end of the observation period. The secondary objective was to assess the clinical course of the disease conditions. Results：Of the 413 patients enrolled, 271 and 254 patients were analyzed for safety and effectiveness, respectively. The mean（SD）treatment duration with ALE DS was 46.9 （31.8）days. Overall, 13 events（ADRs）were reported in 8 patients（2.95％）. No serious ADRs was reported. Neurological ADRs were reported in 2 cases （drowsiness and headache）. There was no between‒group difference in the occurrence of ADRs among the prespecified age and weight subgroups. Improvement rate（improved or markedly improved）as determined by GIS was 70.6％ and 77.5％ at 4‒week treatment after ALE DS initiation and at the end of the observation period, respectively. Conclusions：In this observational study, the use of ALE DS in pediatric patients was associated with an improvement in symptoms of allergic rhinitis, urticaria, and pruritus with a good safety profile.

Background：Tiotropium Respimat®（Tio‒R）is a first long‒acting muscarinic antagonist with bronchial asthma indications in Japan. Objective：To evaluate the safety and effectiveness of Tio‒R in severe persistent asthmatics under general clinical practice. Method：The PMS was conducted over a 52‒week observation period in 359 patients enrolled with severe persistent asthma, aged≧15 years, who were naive to Tio‒R and received Tio‒R for the first time for treatment of bronchial asthma on top of at least inhaled corticosteroid treatment（NCT02489981）. The primary outcome was the incidence of patients with adverse drug reactions（ADRs） over a 52‒week observation period. The secondary outcome was the change from baseline in asthma control status at Week 52. Asthma control status at each visit was determined according to the Japanese guideline for adult asthma. Another outcome was the change from baseline in the Asthma Control Questionnaire（ACQ‒6）score at Week 52. Results：Of 340 patients in the safety set, the incidence of patients with ADR was 5.59％（19/340 patients）. The most frequent ADRs were thirst, cough, dry mouth and dysphonia；each event was reported in 3 of 340 patients［0.88％（3/340 patients）］. Potential factor affecting the incidence of ADR was sex｛2.55％ in male and 8.20％ in female, and odds ratio＝3.42［, 95％ confidential interval（CI）；1.11, 10.51］｝. Regarding the asthma control status at Week 52, for those with insufficient control at baseline, 58.12％（68/117 patients） improved, and for those with poor control at baseline, 57.66％ （64/111 patients） improved. Change from baseline to Week 52 in the ACQ 6 score was－1.59（95％ CI；－1.91, －1.26）, which was statistically significant. Conclusion：The survey supported the effectiveness of long‒term use of Tio‒R（a dose of 5μg once daily） in severe persistent asthmatics and did not discover any clinically relevant safety issue.

Background：Bleeding complications in patients undergoing percutaneous coronary intervention（PCI）affect adverse clinical outcomes. Potassium‒competitive acid blocker（P‒CAB）, an anti‒ulcer drug, has theoretical advantages in metabolization or faster acid suppression over proton pump inhibitors（PPIs）for preventing gastrointestinal bleeding（GIB）；however, their differences in clinical outcomes are unclear. Objective：We sought to compare the efficacy of P‒CAB compared with other PPIs after PCI. Methods：A total of 482 consecutive patients undergoing PCI from 2015 to 2016 at a general hospital were initially included. P‒CAB（n＝86, 19％）and PPI（n＝328, 68％） were prescribed to prevent GIB. The primary endpoint was major bleeding defined as Bleeding Academic Research Consortium type 3 to 5 within 30 days after index PCI. The secondary endpoint was major adverse cardiac events（MACEs）including all‒cause death, non‒fatal myocardial infarction, and target vessel/lesion revascularization at 1 year. Results：The baseline characteristics were similar, although there were more male patients in the P‒CAB group（P‒CAB 82.6％［71/86］vs. PPI 67.1％［220/328］, p＝0.005）. Major bleeding and GIB were similar（major bleeding：1.2％［1/86］vs. 2.7％［9/328］, p＝0.70；GIB：0％［0/86］vs. 0.61％［2/328］, p＞0.99）. The incidence of MACE was 8.1％（7/86）in P‒CAB and 15.9％（52/328）in PPI（p＝0.069）；however, Kaplan‒Meier analysis showed that the incidence of MACE was lower in P‒CAB than in PPI among patients treated with second‒generation drug‒eluting stents （log‒rank test, p＝0.02）. Conclusion：P‒CAB and PPIs showed similar effects in preventing bleeding events.