Efficacy and safety of omalizumab in patients with moderate-to-severe asthma: An analytic comparison of data from randomized controlled trials between Chinese and Caucasians.

BACKGROUND: Omalizumab has > 15 years of real-world evidence of effectiveness in Caucasian patients. In August 2017, it was approved as an add-on therapy for the management of moderate-to-severe asthma in China. OBJECTIVE: To compare the efficacy and safety of omalizumab in Chinese and Caucasian patients. METHODS: This analysis included clinical trial data from a Chinese study (NCT01202903) and four studies with predominantly Caucasian patients (008, 009, EXTRA and INNOVATE). The following outcomes were analyzed: change from baseline in morning peak expiratory flow (mPEF), percentage predicted forced expiratory volume in one second (FEV1), patient-reported outcomes (PROs), asthma exacerbation and safety. Further, a population pharmacokinetic/pharmacodynamic (PK/PD) was also assessed. RESULTS: In the Chinese study, omalizumab significantly improved the mPEF from baseline vs placebo at Weeks > 4-8 through > 16-20; however, the change in mPEF did not reach statistical significance at Week 24. A similar trend towards improvement in mPEF was observed in the studies with Caucasians (INNOVATE, 008 and 009). In all studies, omalizumab showed greater improvement in %predicted FEV1, AQLQ score, and GETE score vs placebo. In addition, asthma symptom scores and seasonal exacerbations were lower, especially during winter, in the Chinese study, and was comparable to studies in Caucasians. PK/PD analyses showed that steady-state PK of omalizumab; free or total immunoglobulin E levels were similar in all studies. CONCLUSIONS: The clinical efficacy and safety of omalizumab was comparable among Chinese and Caucasian patients with moderate-to-severe asthma supporting therapeutic effectiveness, irrespective of race, ethnicity and geographical factors.

Performance Characteristics of Breezhaler® and Aerolizer® in the Real-World Setting.

The evaluation of errors in use with different inhaler devices is challenging to quantify as there are a number of definitions of critical and non-critical errors with respect to inhaler use; in addition, performance characteristics of the device, such as airflow resistance, can also influence effective use in the real-world setting. Repeated observations and checking/correcting inhaler use are essential to optimise clinical effectiveness of inhaled therapy in patients. Breezhaler® is a single unit-dose dry powder inhaler used in chronic obstructive pulmonary disease and in asthma (budesonide) that has low airflow resistance, making it easier for patients of varying disease severities to achieve the inhalation flow rate required for lung deposition of treatment. Similar to Breezhaler®, the Aerolizer® is a single unit-dose dry powder inhaler used in asthma management with low airflow resistance. Studies have shown relatively low rates of critical errors with Breezhaler® and Aerolizer®, with similarities in the critical errors reported; these data on critical errors together with similarities in the usability of Breezhaler® and Aerolizer® further support the functional similarity between the two devices in both asthma and chronic obstructive pulmonary disease. Breezhaler® also has patient-feedback features, including use of a transparent drug capsule that can be checked after inhalation to see it is empty. The low resistance of the dose-confirming Breezhaler® results in less inspiratory effort being required by patients for its effective use, which allows the device to be used effectively across a wide age range of patients and disease severities.

IgE-Mediated Multimorbidities in Allergic Asthma and the Potential for Omalizumab Therapy.

Allergic asthma often coexists with different pathological conditions, called multimorbidities, that are mostly of allergic nature and share a common underlying inflammatory pathophysiological mechanism. Multimorbidities of allergic asthma may influence asthma control, its severity, and patients' response to treatment, and contribute to the overall socioeconomic burden of the disease. Immunoglobulin E (IgE) is known to play a central role in the pathogenesis of various allergic diseases, including asthma. Thus, IgE-mediated immunologic pathways present an attractive target for intervention in asthma and multimorbidities. In this review, we discuss the most frequently reported IgE-mediated multimorbidities in allergic asthma, including allergic rhinitis, rhinoconjunctivitis, atopic dermatitis, vernal keratoconjunctivitis, chronic rhinosinusitis with nasal polyps, food allergies, and allergic bronchopulmonary aspergillosis. Omalizumab is a recombinant humanized monoclonal antibody against IgE and has been in use to treat allergic asthma for more than a decade. We comprehensively review the clinical evidence for omalizumab in the treatment of the aforementioned multimorbidities in allergic asthma.

Long-Term Effects of Safinamide on Mood Fluctuations in Parkinson's Disease.

BACKGROUND: Mood disorders are very frequent in Parkinson's Disease (PD), and their effective treatment is still a major unresolved issue: growing evidence suggests that glutamatergic system dysfunction is directly involved. Safinamide is a drug with an innovative mechanism of action, dopaminergic and non-dopaminergic, that includes the reversible inhibition of the monoamine oxidase-B (MAO-B) enzyme and the modulation of excessive glutamate release through the use- and state-dependent blockade of the sodium channels. OBJECTIVE: To investigate the effects of safinamide on mood over two-year treatment in PD patients with motor fluctuations. METHODS: This was a post-hoc analysis of the data from studies 016 and 018. The analysis focused on outcomes related to mood, namely: scores of the "Emotional well-being" domain of the Parkinson's Disease Questionnaire (PDQ-39), scores of the GRID Hamilton Rating Scale for Depression (GRID-HAMD) and the proportion of patients reporting depression as an adverse event over the entire treatment period. RESULTS: Safinamide, compared to placebo, significantly improved the PDQ-39 "Emotional well-being" domain after6-months (p = 0.0067) and 2 years (p = 0.0006), as well as the GRID-HAMD (p = 0.0408 after 6 months and p = 0.0027 after 2 years). Significantly fewer patients in the safinamide group, compared to placebo, experienced depression as adverse event (p = 0.0444 after 6 months and p = 0.0057 after 2 years). CONCLUSION: The favorable effect of safinamide on mood may be explained by the improvement in wearing off and by its modulation of glutamatergic hyperactivity and reversible MAO-B inhibition. Prospective studies are warranted to investigate this potential benefit.

Omalizumab Improves Quality of Life and Asthma Control in Chinese Patients With Moderate to Severe Asthma: A Randomized Phase III Study.

PURPOSE: Omalizumab is the preferred add-on therapy for patients with moderate-to-severe persistent allergic asthma and has demonstrated efficacy and safety in various ethnicities. This study evaluated the efficacy and safety of omalizumab in Chinese patients with moderate-to-severe allergic asthma. METHODS: This randomized, double-blind, parallel-group, placebo-controlled, phase III study assessed lung function, quality of life, asthma control, and safety of omalizumab after 24-week therapy in Chinese patients (18-75 years of age). RESULTS: A total of 616 patients were randomized (1:1) to omalizumab or placebo. The primary endpoint, least squares mean treatment difference (LSM-TD) in morning peak expiratory flow (PEF) (omalizumab vs placebo), at Weeks >20-24 was 8.85 L/min (Full analysis set; P=0.062). Per-protocol analysis set showed significant improvements with LSM-TD of 11.53 L/min in mean mPEF at Weeks >20-24 (P=0.022). The FEV1 % predicted was significantly improved with omalizumab vs placebo from 8 to 24 weeks (after 24-week treatment: LSM-TD=4.12%; P=0.001). At Week 24, a higher proportion of omalizumab-treated patients achieved clinically relevant improvements in standardized AQLQ (58.2% vs 39.3%; LSM=0.51 vs 0.10; P<0.001) and ACQ (49.5% vs 35.5%; LSM=-0.51 vs -0.34; P=0.002) scores vs placebo. Total and nighttime symptom scores reduced significantly with omalizumab vs placebo (LSM-TD=-0.21, P=0.048 and -0.12, P=0.011, respectively). Although the study was not powered to study differences in exacerbation rates (P=0.097), exacerbations in winter months were less frequent in the omalizumab vs placebo group (2 vs 21). Adverse event and severe adverse event rates were comparable between omalizumab and placebo. CONCLUSIONS: Omalizumab improves lung function, quality of life, and asthma control in Chinese patients with moderate-to-severe persistent allergic asthma and has a good safety profile.

High prevalence of smoking in Northern Greece.

AIM: To investigate the prevalence of smoking in the general population and in specific population sub-groups in Northern Greece. METHODS: A cross-sectional study was conducted during the period 1999-2001 on a 5% sample (23,840) of those people aged between 21 to 80 out of a total general population of 653,249. 21,854/23,840 general population subjects were interviewed. In addition, we interviewed 9,276 high school students, 1,072 medical students, 597 medical doctors within the National Health System, 825 teachers, and 624 subjects who regularly exercised in a privately-owned gym. A specially modified ICRF study group questionnaire was used. RESULTS: 34.4% of the general population sample were current smokers (47.8% of males and 21.6% of females). Smoking prevalence rates in the population sub-groups were: 29.6% of high school students; 40.7% of medical students; 44.9% of medical doctors; 46.4% of teachers; and 36.9% of the gym group. CONCLUSION: The prevalence of smoking in Northern Greece is high. High school and medical students present with high smoking rates, and the same situation is observed in medical doctors and teachers. An intensification of preventive antismoking measures is required.

Use of interrupter technique in assessment of bronchial responsiveness in normal subjects.

BACKGROUND: A number of subjects, especially the very young and the elderly, are unable to cooperate and to perform forced expiratory manoeuvres in the evaluation of bronchial hyperresponsiveness (BHR). The objective of our study was to investigate the use of the interrupter technique as a method to measure the response to provocation and to compare it with the conventional PD20 FEV1. METHODS: We studied 170 normal subjects, 100 male and 70 female (mean +/- SD age, 38 +/- 8.5 and 35 +/- 7.5 years, respectively), non-smoking from healthy families. These subjects had no respiratory symptoms, rhinitis or atopic history. A dosimetric cumulative inhalation of methacholine was used and the response was measured by the dose which increases baseline end interruption resistance by 100% (PD100Rint, EI) as well as by percent dose response ratio (DRR). RESULTS: BHR at a cut-off level of 0.8 mg methacholine exhibited 31 (18%) of the subjects (specificity 81.2%), 21 male and 10 female, while 3% showed a response in the asthmatic range. The method was reproducible and showed good correlation with PD20FEV1 (r = 0.76, p < 0.005), with relatively narrow limits of agreement at -1.39 mumol and 1.27 mumol methacholine, respectively, but the interrupter methodology proved more sensitive than FEV1 in terms of reactivity (DRR). CONCLUSIONS: Interrupter methodology is clinically useful and may be used to evaluate bronchial responsiveness in normal subjects and in situations when forced expirations cannot be performed.