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Masao Yamaguchi,1 Yoshihiro Nishimura,2 Yuko Takumi,3 Nobuya Hayashi,4 Kei Sakamoto,3 Yuji Tohda5 1Division of Respiratory Medicine, Third Department of Medicine, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan; 2Kita-Harima Medical Center, Ono, Hyogo, Japan; 3Patient Safety Division, Research and Development, AstraZeneca K.K., Osaka, Japan; 4Data Science and Innovation Division, Research and Development, AstraZeneca K.K., Osaka, Japan; 5Department of Respiratory Medicine and Allergology, Kindai University School of Medicine, Osaka-Sayama, Osaka, JapanCorrespondence: Masao Yamaguchi, Division of Respiratory Medicine, Third Department of Medicine, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan, Tel +81-436-62-1211, Fax +81-436-62-7340, Email myama@med.teikyo-u.ac.jpIntroduction: This study aimed to demonstrate whether benralizumab maintained the safety and effectiveness profiles established in randomized controlled trials among all patients with severe uncontrolled asthma initially prescribed benralizumab in the real-world setting in Japan.Methods: This was a prospective, observational, multicenter post-marketing study (ClinicalTrial.gov, NCT03588546). The safety and tolerability of benralizumab over 1 year were assessed by the incidence of adverse events (AEs), serious AEs, adverse drug reactions (ADRs), and serious ADRs. Patient background characteristics indicating a more frequent onset of ADRs with benralizumab were explored. The main effectiveness assessment was the change in Asthma Control Questionnaire-5 (ACQ-5) score from baseline. Patients with baseline ACQ-5 scores ≥ 1.5 were defined as having severe uncontrolled asthma.Results: In total, 632 patients were evaluated for safety and 274 for effectiveness; 139 patients were included in the severe uncontrolled asthma subgroup. ADRs were reported in 12.7% and serious AEs in 13.0% of patients. Serious infections occurred in 3.8%, serious hypersensitivity in 0.3%, and malignancy in 0.3% of patients. No helminthic infections occurred. In the effectiveness population, benralizumab improved the mean (standard deviation [95% confidence interval]) ACQ-5 score by − 1.16 (1.40 [− 1.36, − 0.96]) from baseline; forced expiratory volume in 1 second by 0.151 (0.440 [0.09, 0.21]) L; and Mini-Asthma Quality of Life questionnaire score by 1.16 (1.29 [0.94, 1.38]) at the last observation. The annual asthma exacerbation rate was 0.42. A greater ACQ-5 score improvement was observed among patients with eosinophilic asthma characteristics.Conclusion: No new safety concerns were raised, and patients experienced benefits consistent with previous studies of benralizumab, thus supporting the use of benralizumab for the add-on maintenance treatment of patients with eosinophilic severe uncontrolled asthma.Keywords: benralizumab, severe uncontrolled asthma, anti-interleukin-5 receptor α monoclonal antibody, eosinophils, exacerbation, asthma control, quality of life

Soichiro Hanada,1,* Masato Muraki,1,* Yoshiyuki Kawabata,1 Kazuya Yoshikawa,1 Toshiyuki Yamagata,1 Tadao Nagasaki,1 Yushiro Ohara,2 Naoki Oiso,2 Hisako Matsumoto,3 Yuji Tohda4 1Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital, Ikoma, Nara, Japan; 2Department of Dermatology, Kindai University Nara Hospital, Ikoma, Nara, Japan; 3Department of Respiratory Medicine and Allergology, Kindai University Hospital, Osakasayama, Osaka, Japan; 4Kindai University Hospital, Osakasayama, Osaka, Japan*These authors contributed equally to this workCorrespondence: Masato Muraki, Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital, 1248-1 Otoda-cho, Ikoma, Nara, 630-0293, Japan, Tel +81 743 77 0880, Fax +81 743 77 0890, Email muraki-m@med.kindai.ac.jpPatients and Methods: A questionnaire survey was administered to 18, 14, and 3 patients introduced to home self-injection of dupilumab or mepolizumab using a pen-type device for atopic dermatitis, asthma alone, and asthma plus chronic rhinosinusitis with nasal polyps, respectively.Results: All but one participant wished to continue self-injection. Most participants affirmed the reduction in copayment (88.6%) and saving time and labor for hospital visits (88.6%). Six patients who received dupilumab complained of side effects, but all, except for one, continued the treatment. Of the 13 patients who had previously used a syringe-type device, 10 preferred the pen type because of its ease of use, while 3 (23%) preferred the syringe type because of the self-adjustable injection speed for pain control.Conclusion: Administration of biologics using pen-type devices is easier, and the introduction of home self-injection leads to a reduction in outpatient visits and copayment.Keywords: dupilumab, mepolizumab, self-injection, asthma, atopic dermatitis, chronic sinusitis with nasal polyps

Toshiyuki Koya,1 Kazuhisa Asai,2 Takashi Iwanaga,3 Yu Hara,4 Mai Takahashi,5 Naoyuki Makita,5 Nobuya Hayashi,6 Naoki Tashiro,5 Yuji Tohda7,8 1Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; 2Department of Respiratory Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan; 3Center for General Medical Education and Clinical Training, Kindai University Faculty of Medicine, Osakasayama, Japan; 4Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan; 5Medical Department, AstraZeneca KK, Osaka, Japan; 6R&D, AstraZeneca KK, Osaka, Japan; 7Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine, Osakasayama, Japan; 8Kinki Hokuriku Airway disease Conference (KiHAC) Group, Osakasayama, JapanCorrespondence: Toshiyuki Koya, Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-ku, Niigata, 951-8510, Japan, Tel +81 25-368-9325, Fax +81 25-368-9326, Email tkoya@med.niigata-u.ac.jpPurpose: Treatment patterns and patient characteristics are not well elucidated among Japanese patients with severe uncontrolled asthma who currently have various treatment options, including biologics. We analyzed baseline characteristics of patients who did/did not initiate biologic treatment in PROSPECT, a 24-month observational study.Patients and Methods: Patients with severe uncontrolled asthma were prospectively enrolled at 34 sites in Japan from December 2019 to September 2021. The enrolled population was divided based on initiation/non-initiation of biologic treatment within 12 weeks after enrollment. Patient demographics, clinical characteristics, biomarker levels, and asthma-related treatment were assessed at enrollment.Results: Of 289 patients meeting the enrollment criteria, 127 patients initiated biologic treatment (BIO group: omalizumab, n = 16; mepolizumab, n = 10; benralizumab, n = 41; and dupilumab, n = 60) and 162 patients did not (non-BIO group). The proportion of patients with ≥ 2 asthma exacerbations was higher in the BIO group than the non-BIO group (65.0% vs 47.5%). Patients receiving omalizumab had the highest frequency of allergic rhinitis (87.5% vs other BIOs: 40.0%– 53.3%). Patients receiving benralizumab and dupilumab had the highest incidence of nasal polyps (benralizumab: 19.5%, dupilumab: 23.3%, other BIOs: 0.0%). The proportion of patients with blood eosinophils ≥ 300 cells/μL was higher with benralizumab (75.6%) than other BIOs (26.7%– 42.9%).Conclusion: This analysis of baseline data from the PROSPECT study is the first to clarify the characteristics of Japanese patients with severe uncontrolled asthma. BIOs were not necessarily prescribed to patients in whom they were indicated; however, for patients who received them, selection appeared to be made appropriately based on asthma phenotypes.Keywords: benralizumab, biologics, dupilumab, mepolizumab, omalizumab

Akira Yamasaki,1 Katsuyuki Tomita,2 Kazuhiro Kato,3 Kouji Fukutani,3 Hiroyuki Sano,4 Yuji Tohda,4 Eiji Shimizu1 1Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Tottori, 2Department of Respiratory Medicine, Yonago Medical Centre, Tottori, 3Department of Respiratory Medicine, Sanin Rosai Hospital, Tottori, 4Department of Respiratory Medicine and Allergology, Faculty of Medicine, Kinki University, Osaka, Japan Background: Asthma guidelines suggest stepping-down of inhaled corticosteroids (ICSs) when asthma is stable. Objective: To determine outcomes of stepping-down and prediction of outcome after stepping-down of ICSs in controlled adult asthma. Methods: We performed a retrospective study on 21–81 year-old hospital-based outpatients with asthma in Japan. Protocol for stepping-down of ICSs was performed according to the GINA guideline. Failure/success of stepping-down is judged as occurring exacerbation or not for stepping-down of ICSs. Multiple logistic regression analysis was used to develop a prediction model for failed stepping-down, and then was validated by the leave-one-out cross-validation method. Our model of prediction score was calculated using receiver-operating characteristic area under the curve (AUC) analysis. The Nelson–Aalen curve demonstrated time to failure of stepping-down of ICSs. Results: A total of 126 patients with asthma attempted the stepping-down of ICSs according to the guideline. Of patients with follow-up, 97 (77.0%) of stepping-down attempts were successful. Using multivariate logistic regression analysis, comorbidity with rhinitis/rhinosinusitis and phlegm grade were independent predictors of failed stepping-down of ICSs, with odds ratios of 3.8 (95% confidence interval, 1.04–13.3; P=0.04) and 1.3 (95% confidence interval, 1.01–11.5; P=0.04), respectively. These variables were then used to build a prediction score in terms of the prediction of failed stepping-down events. When the two variables were added to form the prediction score, the discriminative power of scores calculated by the prediction model using the AUC was 0.75 (range: 0.62–0.88) for naïve prediction and 0.72 (range: 0.60–0.86) after cross-validation. In the time-to-failure models, cumulative hazard ratio of failed stepping-down have fixed 1 year after stepping-down. Conclusion: Our results suggest that comorbidity with rhinitis/rhinosinusitis and phlegm grade are imperative to predict failed stepping-down of ICSs in controlled patients with adult asthma. Keywords: asthma, ICSs, stepping-down

Soichiro Hanada,1 Shota Wada,1 Takeshi Ohno,1 Hirochiyo Sawaguchi,1 Masato Muraki,1 Yuji Tohda2 1Department of Respiratory Medicine and Allergology, Nara Hospital, Kinki University Faculty of Medicine, Ikoma, 2Department of Respiratory Medicine and Allergology, Kinki University Faculty of Medicine, Osakasayama, Japan Background: Tiotropium (Spiriva) is an inhaled muscarinic antagonist for patients with chronic obstructive pulmonary disease (COPD), and is available in two forms: the HandiHaler and the Respimat inhaler. The aim of this study was to investigate the handling of and preference for each device immediately after switching from the HandiHaler to the Respimat and 2–3 years after the switch.Materials and methods: The study comprised two surveys. A questionnaire was first administered to 57 patients with COPD (male:female 52:5, mean age 73.6±7.1 years) 8 weeks after switching from the HandiHaler (18 µg) to the Respimat (5 µg). A second similar but simplified questionnaire was administered to 39 of these patients who continued to use the Respimat and were available for follow-up after more than 2 years. Pulmonary function was also measured during each period.Results: In the first survey, 17.5% of patients preferred the HandiHaler, and 45.6% preferred the Respimat. There were no significant changes in pulmonary function or in the incidence of adverse events after the switch. In the second survey, performed 2–3 years later, the self-assessed handling of the Respimat had significantly improved, and the number of patients who preferred the Respimat had increased to 79.5%.Conclusion: The efficacy of the Respimat was similar to that of the HandiHaler. This was clear immediately after the switch, even in elderly patients with COPD who were long-term users of the HandiHaler. The preference for the Respimat increased with continued use. Keywords: chronic obstructive pulmonary disease, tiotropium, HandiHaler, Respimat, questionnaire, pulmonary function

Takeshi Ohno,1 Shota Wada,1 Souichirou Hanada,1 Hirochiyo Sawaguchi,1 Masato Muraki,1 Yuji Tohda21Department of Respiratory Medicine and Allergology, Nara Hospital, Kinki University Faculty of Medicine, Ikoma, Japan; 2Department of Respiratory Medicine and Allergology, Kinki University School of Medicine, Osakasayama, JapanBackground: Indacaterol is a novel, once-daily, inhaled, long-acting β2-agonist for patients with chronic obstructive pulmonary disease (COPD). The study objective was to evaluate the efficacy of indacaterol on quality of life and pulmonary function in patients with COPD in a real-world setting, and also to evaluate its inhaler device (Breezhaler®), which is important for both adherence and management.Methods: Twenty-eight outpatients with COPD were treated with indacaterol (150 µg once daily for 8 weeks), and the effects on pulmonary function were evaluated using a questionnaire survey with the modified Medical Research Council (mMRC) dyspnea scale and COPD assessment test (CAT) before and after treatment. Similar investigations were also performed separately among different baseline medications. Moreover, original questionnaire surveys for indacaterol and its device were performed.Results: Overall, mMRC dyspnea scale and CAT scores significantly improved (1.96±1.04 to 1.57±1.07 and 17.39±8.23 to 12.82±8.42, respectively; P