Real-world safety and effectiveness of omalizumab in Japanese patients with chronic spontaneous urticaria: A post-marketing surveillance study.

BACKGROUND: The safety and efficacy of omalizumab in chronic spontaneous urticaria (CSU) patients has been established, but real-world long-term data remain scarce, especially in Japan. METHODS: 52-week, open-label, single-arm, observational study evaluated the safety and effectiveness of first-time omalizumab in Japanese CSU patients responding inadequately to conventional therapies. RESULTS: Overall, 235 of 280 patients completed the study. Most patients were aged ≥ 18 and < 65 years; adolescents (≥ 12 and ≤ 18 years) accounted for 9.6% of the total population. The mean ± standard deviation (SD) duration of CSU at baseline was 1.6 ± 3.1 years; 46.1% of patients had had CSU for < 6 months. At baseline, the mean ± SD of Urticaria Control Test (UCT) score, Weekly Urticaria Activity Score (UAS7), and Dermatology Life Quality Index (DLQI) were 5.1 ± 3.2, 25.2 ± 11.9, and 8.4 ± 5.9, respectively. The mean ± SD duration of the observation period was 330.3 ± 86.2 days. Relapse was reported in 65 patients, 51, 9, and 5 of whom required retreatment with omalizumab 1, 2, and ≥ 3 times, respectively. The incidence of adverse events (AEs), serious AEs, and adverse drug reactions (ADRs) was reported in 11.8%, 1.4%, and 3.9% of patients, respectively. The most common AEs were urticaria (1.8%) and eczema (1.1%). No adolescents experienced ADRs. A cumulative of 92.8% of patients responded in the Physician's Global Impression of Change, with 81.3%, 75.0%, and 95.1% of patients achieving UCT ≥ 12, UAS7 ≤ 6, and DLQI ≤ 5 up to Week 52, respectively. CONCLUSIONS: This study supports the safety and effectiveness of omalizumab in CSU patients who responded inadequately to conventional therapies in real-world clinical practice in Japan.

Real-world safety and effectiveness of canakinumab in patients with cryopyrin-associated periodic fever syndrome: a long-term observational study in Japan.

OBJECTIVES: A post-marketing all-patient surveillance program was conducted to evaluate the safety and effectiveness of canakinumab, a monoclonal anti-interleukin-1ß antibody, in patients in Japan with cryopyrin-associated periodic fever syndrome (CAPS), including familial cold auto-inflammatory syndrome, Muckle-Wells syndrome, and neonatal onset multisystem inflammatory disease. METHODS: All patients with CAPS who received canakinumab treatment after drug approval in Japan were registered in this non-interventional, observational study. The observation period per patient was two years. Patients newly treated with canakinumab (New patients; NP) and those continuously treated with canakinumab following clinical trials (Roll-over patients; RP) were included. Data collection of clinical symptoms affecting physical function and prognosis was not mandated but assessed where available. Here, the interim results are reported. RESULTS: Of 87 patients in the safety set, the proportion of patients with any adverse drug reactions (ADRs) and any serious ADRs was 31.03% and 3.45%, respectively. The most common ADRs reported under system organ class were infections and infestations (20.69%). Of 84 patients in the effectiveness set, 75.76% and 83.33% of NP and RP, respectively, were responders at Week 24, achieving complete response without relapse. Responder rates were maintained up to Week 104. Clinical symptoms affecting physical function and prognosis remained unchanged in over half of those patients. CONCLUSIONS: Interim results provided the safety profile of canakinumab in a real-world setting, and identified no new safety concerns. Treatment with canakinumab has suggested sustained remission in the majority of patients in the real-world setting.

Efficacy of sacubitril/valsartan versus olmesartan in Japanese patients with essential hypertension: a randomized, double-blind, multicenter study.

This phase III study assessed the efficacy and safety of sacubitril/valsartan compared with those of olmesartan in Japanese patients with essential hypertension. Patients (n = 1161, aged ≥20 years) with mild to moderate hypertension (mean sitting systolic blood pressure [msSBP] ≥150 to <180 mmHg) were randomized to receive sacubitril/valsartan 200 mg (n = 387), sacubitril/valsartan 400 mg (n = 385), or olmesartan 20 mg (n = 389) once daily for 8 weeks. The primary assessment was a reduction in msSBP from baseline with sacubitril/valsartan 200 mg vs. olmesartan 20 mg at Week 8. Secondary assessments included msSBP reduction with sacubitril/valsartan 400 mg vs. olmesartan at Week 8 and reductions in mean sitting diastolic blood pressure (msDBP), mean sitting pulse pressure (msPP), and overall blood pressure (BP) control rate for all treatment groups at Week 8. Sacubitril/valsartan 200 mg provided a significantly greater reduction in msSBP from baseline than olmesartan at Week 8 (between-treatment difference: -5.01 mmHg [95% confidence interval: -6.95 to -3.06 mmHg, P < 0.001 for noninferiority and superiority]). Greater reductions in msSBP with sacubitril/valsartan 400 mg vs. olmesartan, as well as in msDBP and msPP with both doses of sacubitril/valsartan vs. olmesartan (P < 0.05 for all), were also observed. Patients treated with sacubitril/valsartan achieved an overall higher BP control rate. The safety and tolerability profiles of sacubitril/valsartan were generally comparable to those of olmesartan. The adverse event rate with sacubitril/valsartan was not dose-dependent. Treatment with sacubitril/valsartan was effective and provided superior BP reduction, with a higher proportion of patients achieving target BP goals than treatment with olmesartan in Japanese patients with mild to moderate essential hypertension.

Real-world Safety and Efficacy of Indacaterol/Glycopyrronium in Japanese Patients with Chronic Obstructive Pulmonary Disease: A 52-week Post-marketing Surveillance.

Objective To evaluate the long-term safety and efficacy of indacaterol/glycopyrronium (IND/GLY) in patients with chronic obstructive pulmorary disease (COPD) in a real-world setting in Japan. Methods This 52-week, multicentre, post-marketing surveillance conducted in Japan between December 2013 and August 2019 included patients using IND/GLY for the first time to relieve airway obstructive disorder-related symptoms. Safety outcomes included the incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), and serious ADRs during the 52-week period. The incidence of priority variables, including cardiovascular/cerebrovascular (CCV) AEs, ß-adrenergic-related or anticholinergic AEs and cough, was also assessed. Safety outcomes were also evaluated in elderly patients. Efficacy outcomes included a physician's global assessment, COPD assessment test (CAT) and lung function test. Results Of the 1,167 patients registered, 1,108 were included in the safety and efficacy analysis. In the safety analysis population, the incidence of AEs was 13.54%, that of SAEs was 4.69%, that of ADR was 3.61%, and that of serious ADRs was 0.36% over 52 weeks. CCV AEs, ß-adrenergic-related and anticholinergic AEs and cough were reported as 2.62%, 1.99% and 0.63%, respectively. The physician's global assessment showed that the overall response rate at the last assessment was 74.19%. The mean (95% confidence interval) CAT scores decreased from the start of treatment to Week 52 with IND/GLY [-6.9 (-7.8 to -6.1)]. The lung function (FEV1 and FVC) improved over time from the start of IND/GLY to Week 52. Conclusion IND/GLY demonstrated a good long-term safety profile in a real-world setting in Japanese patients with COPD, with beneficial effects in terms of the lung function and symptoms in clinical use.

Real-World Safety and Efficacy of Glycopyrronium Bromide in Japanese Patients with COPD: A 52-Week Post-Marketing Surveillance.

Objective: To evaluate the long-term safety and efficacy of glycopyrronium (GLY) in patients with COPD in a real-world setting in Japan. Methods: This 52-week, multicentre, post-marketing surveillance conducted in Japan, between February 2013 and August 2019, included patients using GLY for the first time for the relief of airway obstructive disorder-related symptoms. Safety outcomes included incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), serious ADRs (SADRs) and priority variables included cardiovascular/cerebrovascular (CCV) AEs and anticholinergic AEs during the 52-week period. Safety outcomes were also assessed in elderly patients. Efficacy outcomes included physician's global assessment, COPD assessment test (CAT) and lung function test. Results and Discussion: Of the 1,331 patients registered for this surveillance, safety and efficacy outcomes were evaluated in 1,277 patients. In the safety analysis population, the incidence of AEs was 15.51%, SAEs 4.70%, ADRs 5.01% and SADRs 0.31%. The CCV AEs and anticholinergic AEs were reported by 0.70% and 2.58% patients, respectively. Physician's global assessment showed that the overall response rate at the last assessment was 70%. The mean (95% CI) CAT scores decreased from the start of treatment to Week 52 with GLY, (-6.2 [-7.0 to -5.4]). Lung function in terms of trough FEV1 and FVC improved over time from the start of GLY to Week 52. Conclusion: GLY demonstrated an acceptable long-term safety profile with no new safety concerns in a real-life setting. It demonstrated improvement in lung function and symptom control in Japanese COPD patients.

Real-world Safety and Efficacy of Indacaterol Maleate in Patients with Chronic Obstructive Pulmonary Disease: Evidence from the Long-term Post-marketing Surveillance in Japan.

Objective Evidence concerning the safety and efficacy of indacaterol maleate in a real-life setting is limited. The objective of this post-marketing surveillance was to evaluate the real-life safety and efficacy of indacaterol maleate in Japanese patients with chronic obstructive pulmonary disease (COPD). Methods This was a 52-week post-marketing surveillance conducted between April 2012 and December 2018. The safety endpoints included the incidence of adverse events (AEs), serious adverse events (SAEs), and adverse drug reactions (ADRs). The efficacy endpoints included the physician-reported global evaluation of treatment effectiveness (GETE), change from baseline in the COPD assessment test (CAT) results, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and %FEV1 following 4, 12, 26, and 52 weeks of indacaterol administration. Results Of the 1,846 enrolled patients, 1,726 were included in the safety and efficacy analyses. The mean age of the patients was 72.5 years old. Cough, pneumonia and COPD worsening were the most common AEs reported, while pneumonia (1.04%) was the most common SAE, and cough (1.68%) was the most common ADR. GETE showed that 69.70% of patients achieved an excellent/good/moderate response following indacaterol treatment. The CAT score decreased, and lung function parameters (FVC, FEV1 and %FEV1) improved across all the COPD stages following treatment with indacaterol. Conclusion Indacaterol showed a favorable safety and tolerability profile in Japanese patients with COPD without new safety signals observed in real-life settings. These findings demonstrated that indacaterol is an effective maintenance treatment in real-life practice for Japanese patients with COPD.

Real-life long-term safety and effectiveness of omalizumab in Japanese pediatric patients with severe allergic asthma: A post-marketing surveillance.

BACKGROUND: Omalizumab is approved as add-on therapy for pediatric asthma since 2013 in Japan, however, its data in clinical practice is limited. This post-marketing surveillance aimed to evaluate long-term safety and effectiveness of omalizumab in Japanese pediatric patients with severe allergic asthma in real-life setting. METHODS: This 104-week, multicenter surveillance was conducted from September 2013 to May 2019 by central registration method. Patients with severe allergic asthma aged ≥6 and < 15 years at initiation of treatment who were first-time omalizumab users were included. The primary endpoints included incidence of adverse drug reactions and physician's Global Evaluation of Treatment Effectiveness (GETE). The secondary endpoints included incidence of serious adverse events, adverse events and adverse drug reactions of special interest and asthma exacerbation-related events. RESULTS: Of the 128 patients enrolled, 127 completed the surveillance and were included for safety and effectiveness analysis. Thirteen patients experienced 20 adverse drug reactions with an incidence rate of 10.2%. The most frequent adverse drug reactions were pyrexia (2.4%) and urticaria (1.6%). In total, adverse events and serious adverse events occurred in 60 (47.2%) and 30 patients (23.6%) respectively. Two patients experienced anaphylactic reaction and 1 patient experienced type 1 hypersensitivity. 77.2% had an effective response to omalizumab according to GETE at final assessment, and frequency of all asthma exacerbation-related events decreased in post-treatment versus pre-treatment. CONCLUSIONS: Long-term omalizumab treatment showed no new safety signals in pediatric patients with severe allergic asthma. The observed safety and effectiveness profile was consistent with previous studies.

Real-life safety and efficacy of omalizumab in Japanese patients with severe allergic asthma who were subjected to dosing table revision or expansion: A post-marketing surveillance.

BACKGROUND: Omalizumab is an anti-immunoglobulin E monoclonal antibody approved for patients with severe allergic asthma in Japan. With regard to omalizumab dosage in Japanese adults with severe allergic asthma in clinical practice settings, this post-marketing surveillance evaluated safety and efficacy of the dosing table revision (DTR) based on a dosing regimen of omalizumab administration every 4 weeks dosing regimen and dosing table expansion (DTE) for patients with baseline IgE levels >700 IU/mL. METHODS: This 52-week, multicenter study, conducted from September 2013 to November 2018, evaluated omalizumab safety outcomes including adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), efficacy outcomes including Global Evaluation of Treatment Effectiveness (GETE), change in oral corticosteroid dose, and asthma exacerbation-related events such as hospitalization, emergency room visits, and worsening of symptoms. RESULTS: Of the 405 patients registered in the study, safety was evaluated in 392 and efficacy in 390. The mean age of patients was 58.5 years and 58.7% were women. In total, 41.3% of the patients were subjected to DTE and 58.7% to DTR. In the safety dataset, 6.6% experienced an ADR, 32.9% experienced an AE, and 16.1% experienced an SAE. In the efficacy dataset, 63.3% of patients at Week 16 and 63.5% at Week 52 had an 'effective' or 'good' GETE score. Omalizumab was associated with a reduction in worsening of asthma symptoms requiring systemic corticosteroids and frequency of hospitalization. All outcomes were comparable among the DTE and DTR subgroups. CONCLUSION: The findings from this study support the safety and efficacy of omalizumab administered based on the revised and expanded dosing table in Japanese patients with severe allergic asthma.

Cardiovascular safety and effectiveness of vildagliptin in patients with type 2 diabetes mellitus: a 3-year, large-scale post-marketing surveillance in Japan.

Objectives: The dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin is indicated for type 2 diabetes mellitus (T2DM). However, the long-term safety, effectiveness, and clinical relationship with cardiovascular events of vildagliptin have not been evaluated in Japan.Methods: The authors conducted post-marketing surveillance (PMS) to evaluate the safety and effectiveness of vildagliptin in more than 3000 Japanese T2DM patients for up to 3 years. Main assessments included demographics, major adverse cardiovascular events (MACE), adverse events (AEs), adverse drug reactions (ADRs), and glycated hemoglobin (HbA1c).Results: In this PMS, 3831 patients (775 sites) were registered in April 2010 - April 2012. The safety analysis population comprised 3769 patients; 2085 patients were aged ≥65 years, and 240, 411, and 114 had renal impairment, hepatic impairment, and heart failure, respectively. The median treatment duration was 2.7 years. The incidence of MACE was 6.04 cases/1000 person-years, mostly attributable to cerebrovascular events (4.27 cases/1000 person-years). The AE and ADR incidences were 26.0% and 5.3%, respectively. The incidence of hypoglycemia was 0.6%. No significant changes in body weight occurred and mean change in HbA1c from baseline at final assessment was -0.74 ± 1.41% (p < 0.0001).Conclusions: In real-world clinical settings, vildagliptin was well tolerated, with similar profiles as previously reported.

Real-world safety and efficacy of omalizumab in patients with severe allergic asthma: A long-term post-marketing study in Japan.

BACKGROUND: Omalizumab (anti-IgE monoclonal antibody) is an approved add-on therapy for Japanese patients with severe allergic asthma. As directed by the Ministry of Health, Labor and Welfare Japan, a post-marketing surveillance (PMS) study on omalizumab was conducted between 2009 and 2017. METHODS: The PMS observed safety and efficacy of omalizumab in patients treated with open-label omalizumab for 52 weeks (with optional 2-year extension period). Primary safety outcomes included incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs). Primary efficacy outcomes included physician-assessed global evaluation of treatment effectiveness (GETE). Asthma-exacerbation-related events including requirement for additional systemic steroid therapy, hospitalization, emergency room visits, unscheduled doctor visits, and absenteeism were also evaluated. RESULTS: Of 3893 patients registered, 3620 (age [mean ±â€¯SD] 59.3 ±â€¯16.11 years) were evaluated for 52 weeks; 44.12% were aged ≥65 years and 64.45% were women. Overall, 32.24% reported AEs and 15.30% reported serious AEs. ADRs were seen in 292 (8.07%) patients. GETE results showed that the majority of patients experienced clinical improvements (58.29% at 16 weeks and 62.40% at 52 weeks). Nearly half of all patients (47.96%) were free from asthma exacerbations after therapy. Omalizumab also reduced all events related to asthma exacerbations. No specific ADRs were observed in the elderly population. CONCLUSIONS: This post-marketing study confirmed the clinically meaningful benefits of omalizumab in a majority of patients from Japan, and showed safety and efficacy in a real-life clinical setting to be consistent with previous reports.