Omalizumab in patients with severe asthma: the XCLUSIVE study.

BACKGROUND AND AIMS: Although the efficacy and safety of omalizumab (OMA) in uncontrolled severe allergic asthma has been demonstrated in several randomised controlled trials (RCTs), information on the treatment in a practice-related setting is limited. Thus, the purpose of this prospective multi-centre study (XCLUSIVE) was to investigate the efficacy, compliance and utilisation of OMA therapy in real-life clinical practice in Germany. METHODS: One hundred ninety-five asthmatic patients initiated on anti-Immunoglobulin E (IgE) IgE treatment were followed-up for 6 months. Forced expiratory volume in 1 s (FEV(1) ), exacerbation rate, days of absence, asthma symptoms [Asthma Control Questionnaire (ACQ)], a Global Evaluation of Treatment Effectiveness (GETE) and medication use were assessed. RESULTS: Measured outcome variables improved after a 16-week treatment period with OMA (FEV(1) +13.7% predicted P < 0.05, exacerbation rate -74.9% P < 0.0001, days of absence -92.1% P < 0.001, ACQ -43.7% P < 0.0001). Investigators evaluated the effectiveness of OMA by GETE in 78.8% as excellent or good (responder), and in 12.6%/8.6% as moderate/poor or worse (non-responder). Responders demonstrated better improvement of FEV(1), exacerbation rate, days of absence, ACQ and reduction of oral corticosteroids compared with non-responders. CONCLUSION: Results of effectiveness strongly suggest that the efficacy demonstrated in RCTs can be transposed to a clinical practice-related setting.

Long term effects of comprehensive cardiac rehabilitation in an inpatient and outpatient setting.

OBJECTIVES: To compare the long-term effects of comprehensive outpatient versus inpatient rehabilitation with respect to morbidity and mortality, as well as to changes in physical performance and physical activity. DESIGN: A total of 163 consecutive patients were enrolled for comprehensive cardiac rehabilitation (CCR) following a recent coronary event, to outpatient or inpatient CCR according to treatment preference because randomisation was accepted by only 4 patients. CCR was six hours per day for 4 weeks and consisted of exercise training, education, psychological support, and nutritional and occupational advice. Examinations were before, after and 12 months after CCR. Primary outcome measures were event-free survival with or without interventions, EFS-I or EFS, respectively, 12 months after rehabilitation. RESULTS: Main patient characteristics were distributed equally in the cohorts. Results were adjusted by logistic regression for age, BMI, LV-function, exercise capacity and physical activity before the event. Adjusted EFS, EFS-I , overall survival and other morbidity outcome measures did not differ significantly. During CCR, physical activity was higher in outpatients, but this difference was not maintained in the follow up. Average physical activity was increased 12 month after CR with no difference between groups. CONCLUSION: Although influenced by patient preference, participation in either inpatient or outpatient CCR led to comparable results in terms of all-cause or cardiac overall survival, event-free survival and other secondary outcome measures like cardiac morbidity, physical performance and increased physical activity.

Effectiveness of omalizumab in patients 50 years and older with severe persistent allergic asthma.

BACKGROUND: Omalizumab is approved for the treatment of severe allergic asthma. OBJECTIVES: To compare the efficacy of omalizumab therapy in patients 50 years or older with patients younger than 50 years. METHODS: Between November 2005 and November 2007 a total of 174 asthma patients 50 years or older (40.7% male, 51.1% taking oral corticosteroids, and mean [SD] serum IgE level of 315 [353] U/L) and 297 asthma patients younger than 50 years (40.0% male, 50.5% taking oral corticosteroids, and mean [SD] serum IgE level of 363 [431] U/L) who met the European Union criteria for add-on therapy with anti-IgE were treated prospectively with omalizumab for 4 months as part of 2 postmarketing surveillance trials. RESULTS: Compared with the pretrial period omalizumab treatment reduced the rate of severe exacerbations in patients 50 years or older by 68.9% (P < .001) and in patients younger than 50 years by 75.4% (P < .001). After 4 months there was a marked reduction of daily asthma symptoms and nocturnal awakenings by 67.8% and 72.6% in the older and by 79.3% and 82.5% in the younger patients, respectively (P < .001, all 4 comparisons). In 60% of patients 50 years or older lung function improved compared with 69% of patients younger than 50 years. Efficacy of omalizumab was rated as excellent or good by most physicians in patients 50 years or older (68.4%) and younger than 50 years (76.8%, P = .05 elderly vs younger). Adverse events were reported in 35.5% of patients 50 years or older and 32.1% of patients younger than 50 years. There was a higher rate of discontinuation of omalizumab therapy in older patients (20.9% vs 11.1%, P = .006). CONCLUSIONS: The present study confirms the clinical efficacy of omalizumab in patients with severe allergic asthma irrespective of age in a real-life setting outside the omalizumab trial program.

Circulating biomarkers of tissue remodelling in pulmonary hypertension.

OBJECTIVE: Besides persisting high pulmonary arterial pressure and increased pulmonary vascular resistance, remodelling of pulmonary tissues and subsequently the right heart are the key pathomechanisms of pulmonary hypertension (PH). Extracellular matrix maintenance in this context plays a central role. METHODS: We tested the hypothesis that plasma concentration of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinases (TIMP)-4 and tenascin C (TNC) might be useful as biomarkers for assessing the severity of PH. Therefore, the concentrations of MMP-2, TIMP-4, TNC and N-terminal b-type natriuretic peptide (NT-proBNP) of 36 PH patients were compared with those of 44 age- and gender-matched healthy volunteers. Additionally, lung function, 6-min walk distance and right heart function were assessed. RESULTS: In PH patients, significantly elevated plasma levels of MMP-2, TIMP-4, TNC and NT-proBNP were detected. In particular, TIMP-4 was significantly increased in patients with higher NYHA classification, and in patients with severe right ventricular hypertrophy. CONCLUSION: Monitoring of plasma TIMP-4 and to a lesser extent of MMP-2 and TNC levels in PH patients might help to assess the beneficial effects of PH pharmacotherapy on tissue remodelling.

Efficacy and safety of combination chemotherapy with mitomycin and vinorelbine for the treatment of advanced non-small cell lung cancer.

BACKGROUND: Aim of this study was to evaluate efficacy, toxicity and tolerability of chemotherapy with a combination of mitomycin and vinorelbine (M/V) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: We enrolled 110 patients (median age 67 years) with locally advanced or metastatic NSCLC, who had no prior chemotherapy or progressive disease after at least one prior chemotherapy regimen. 45 patients (41%) were > or =70 years old. All patients received vinorelbine 25mg/m(2) (d1,8) and mitomycin 8mg/m(2) (d1) every 3-4 weeks. Restaging was performed by CT-scan after every two courses M/V according to RECIST criteria. RESULTS: M/V was well tolerated, even in patients with a poor performance status or > or =70 years Median progression free survival was 4.4 months. Median overall survival was 9.0 months with a 1-year survival rate of 39%. Partial response was observed in 15% and stable disease in 51% of patients. Both hematological and non-hematological toxicities were generally mild. CTC grade 3 toxicities observed included neutropenia in 3%, anemia in 3%, thrombocytopenia in 1% and suspected pneumonitis in 2% of patients. Except neutropenia in 2% and acute dyspnea in 1%, there were no other grade 4 toxicities and no treatment associated casualties. There was no relevant difference in outcome or toxicity between patients > or =70 and <70 years. CONCLUSIONS: M/V seems to be a well-tolerated and effective chemotherapy regimen with low toxicity in patients with advanced NSCLC. It seems to be an interesting option even for patients > or =70 years or with a reduced performance status.