Real-life efficacy and safety of omalizumab in Portuguese patients with persistent uncontrolled asthma.

INTRODUCTION: The real life effectiveness, safety and the use of omalizumab for Portuguese patients with uncontrolled persistent allergic asthma are not sufficiently well known. The objective of this report was to make an evaluation, in a post-marketing, non-interventional, observational registry, of the Portuguese population included in the eXpeRience study. METHODS: The methods used in this report are the same as the global eXpeRience ones, applied to a Portuguese sub-population. Patients with uncontrolled allergic asthma who had started omalizumab within the previous 15 weeks were enrolled and received omalizumab add-on therapy for 24 months. The physicians' global evaluation of treatment effectiveness (GETE), asthma symptoms and control (ACT score), quality of life (mini-AQLQ score), exacerbations, and serious adverse events (SAE) were reported. RESULTS: Of the 943 patients recruited in the eXpeRience registry, 62 patients were from Portugal. 62.1% of them were observed to be responders with good/excellent GETE assessment at Week 16. Clinically meaningful improvements in asthma control (ACT score) and quality of life (mini-AQLQ score) were observed with omalizumab therapy at Months 12 (mean change: +7.7 [n=35]; +2.1 [n=20], respectively) and 24 (mean change: +7.0 [n=26]; +2.7 [n=13], respectively). Asthma symptoms and rescue medication usage were reduced to ≤1 day/week at Month 24 from a baseline of ≥3.5 days/week. The proportion of patients with no clinically significant exacerbations increased from 6.5% during pre-treatment (n=62) to 50% at Month 12 (n=54) and 60% at Month 24 (n=45). CONCLUSION: The findings from the Portugal subpopulation of eXpeRience registry confirm that omalizumab add-on therapy is efficacious and well tolerated in the management of uncontrolled persistent allergic asthma. Another pertinent issue is the fact that the Portuguese subpopulation response is similar to the international population average of the study.

The eXpeRience registry: the 'real-world' effectiveness of omalizumab in allergic asthma.

Omalizumab has demonstrated therapeutic benefits in controlled clinical trials. Evaluation of outcomes in real-world clinical practice is needed to provide a complete understanding of the benefits of omalizumab treatment. eXpeRience was a 2-year, international, single-arm, open-label, observational registry that evaluated real-world effectiveness, safety and use of omalizumab therapy in 943 patients with uncontrolled persistent allergic asthma. Effectiveness variables (physician's Global Evaluation of Treatment Effectiveness [GETE], and change from baseline in exacerbation rate, symptoms, rescue medication use, and oral corticosteroid [OCS] use) were evaluated at pre-specified time-points. Safety data were also recorded. By physician's GETE, 69.9% of patients were responders to omalizumab after 16 (±1) weeks. The proportion of patients with no clinically significant exacerbations increased from 6.8% during the 12-month pre-treatment period to 54.1% and 67.3% at Months 12 and 24, respectively. Symptoms and rescue medication use at Month 24 were reduced by >50% from baseline. Maintenance OCS use was lower at Month 24 (14.2%) compared with Month 12 (16.1%) and baseline (28.6%). Overall, omalizumab had an acceptable safety profile. The results from eXpeRience indicate that omalizumab was associated with improvements in outcomes in patients with uncontrolled persistent allergic asthma; these improvements were consistent with the results of clinical trials.

Persistency of response to omalizumab therapy in severe allergic (IgE-mediated) asthma.

BACKGROUND: The physician's global evaluation of treatment effectiveness (GETE) at 16 weeks has been shown to be the most effective assessment of response to omalizumab (XOLAIR®). This randomized, open-label, parallel-group study evaluated the persistency of treatment responder classification in patients receiving omalizumab added to optimized asthma therapy (OAT). METHODS: Patients (12-75 years, n = 400) with severe allergic asthma, uncontrolled despite Global Initiative for Asthma 2004 Step 4 therapy, received OAT and omalizumab (n = 272) or OAT (n = 128) for 32 weeks. Response or nonresponse was evaluated at Weeks 16 and 32. Response was defined as an investigator's (physician's) GETE rating of excellent or good; nonresponse was defined as a rating of moderate, poor or worsening. RESULTS: Three hundred and forty-nine patients had GETE ratings available at Weeks 16 and 32 (omalizumab n = 258, OAT n = 91). Omalizumab responders of about 171/187 (91.4%)and 44/71 (62.0%) omalizumab nonresponders at Week 16 persisted as responders or nonresponders at Week 32. The investigator's GETE at Week 16 predicted persistency of response or nonresponse to omalizumab at Week 32 for 83.3% (215/258) of patients. OAT patients showed a lower persistency of response (18/28 [64.3%]) and a higher persistency of nonresponse (57/63 [90.5%]) than omalizumab patients. Excellent and good GETE ratings in omalizumab-treated patients were reflected by improvements in exacerbation rates (P < 0.001), severe exacerbation rates (P = 0.023), hospitalizations (P = 0.003), total emergency visits (P = 0.026) and Asthma Control Questionnaire overall score (P < 0.001). CONCLUSION: Response to omalizumab, as assessed by a physician's GETE at 16 weeks, is an effective predictor of continuing persistent response to omalizumab for the majority of patients.

Omalizumab reduces oral corticosteroid use in patients with severe allergic asthma: real-life data.

BACKGROUND: Long-term oral corticosteroid (OCS) therapy is associated with significant burden on patients and healthcare resources; treatments that may help reduce their use are important to improve asthma management. METHODS: French and German clinicians prescribing omalizumab for >16 weeks to patients with severe persistent allergic asthma collected OCS use data. OCS use was recorded at baseline and at a non-specific time point beyond 16 weeks from initiation of omalizumab. The number of asthma exacerbations (FEV(1) < 60% of personal best, requiring OCS burst and unscheduled doctor/emergency visit or hospitalization) and asthma-related hospitalizations during the 12-months prior to omalizumab treatment and during the observation period were also recorded. RESULTS: Overall, 346 patients were treated with omalizumab for >16 weeks. Of these, 166 (48.0%) were receiving maintenance OCS (France, n = 64; Germany, n = 102). Following omalizumab therapy, 84 (50.6%) patients on OCS at baseline reduced/stopped OCS dose at the time of data collection; 34 (20.5%) stopped and 50 (30.1%) reduced OCS. In all patients receiving maintenance OCS at baseline, mean reduction from baseline in daily OCS dose was 29.6% (7.1 mg prednisolone). In patients who reduced/stopped maintenance OCS, mean reduction from baseline in daily OCS dose was 74.3% (15.4 mg prednisolone). Reductions in exacerbations and hospitalizations were observed from the 12-months prior to baseline in patients at the time of data collection, irrespective of change in OCS dose. CONCLUSION: European real-life experience demonstrates the OCS-sparing potential of omalizumab in some patients with severe allergic (IgE-mediated) asthma.

Bronchodilator effects of indacaterol and formoterol in patients with COPD.

BACKGROUND: Resting inspiratory capacity (IC) reflects static hyperinflation in chronic obstructive pulmonary disease (COPD). This study compared the effects of formoterol and indacaterol, a novel once-daily ultra-long-acting beta(2)-agonist (or ultra-LABA), on resting IC and forced expiratory volume in 1 s (FEV(1)). METHODS: Thirty patients with COPD (mean FEV(1)/FVC 0.49, mean FEV(1) 56% predicted) each inhaled three treatments (two in randomized sequence followed by open-label formoterol) on separate study days: a single dose of indacaterol 300 microg, matching placebo, and two doses of formoterol 12 microg 12 h apart. RESULTS: Indacaterol and formoterol increased FEV(1) and IC at all time points relative to placebo (p<0.001). Peak effects on FEV(1) were similar, while indacaterol had a greater effect on peak IC (31% vs 23% from pre-dose; p=0.034). Indacaterol had a greater effect than formoterol on FEV(1) at 8 h (1.47 vs 1.39 L; p=0.014) and 24 h (1.44 vs 1.35 L; p=0.003), and on IC from 4 to 24 h (differences of 0.13-0.19 L; p<0.05). At 24 h, indacaterol and formoterol increased FEV(1) by 17.7% and 7.5%, respectively, from pre-dose. CONCLUSIONS: This study discriminated between the effects on IC and FEV(1) of once daily indacaterol and twice daily formoterol. The greater effect of indacaterol on IC may translate into improved long-term clinical outcomes.

Repetitive inhalation endotracheal anaesthesia for cobalt radiotherapy in a child.

PURPOSE: Provision of general anaesthesia in areas remote from the operating room creates many difficult challenges especially if required for repeated radiotherapy in the prone position. This case illustrates these problems and some innovative solutions. CLINICAL FEATURES: A nine-year-old girl with medulloblastoma became extremely distressed whenever cobalt radiotherapy was attempted. Sedation with midazolam and high dose propofol infusion failed to achieve satisfactory conditions and caused concerns regarding airway management. The patient received a total of 37 endotracheal anaesthetics in the prone position using isoflurane in oxygen. Activated charcoal was used to scavenge anaesthetic vapors and adequate gas supplies were assured by connecting an "H' size tank to the oxygen pipeline inlet of the anaesthesia machine. Measurement of isoflurane in exhaust gases using gas chromatography confirmed the effectiveness of scavenging. No serious complications occurred related to repeated anaesthesia. CONCLUSION: The methods and equipment described permitted safe delivery of repeated inhalation general anaesthesia for radiotherapy. The same methods could be applied to anaesthesia in other remote locations.

Measuring rebreathing in spontaneous ventilation. A new lung model.

The performance of breathing systems is tested by means of physical lung models. We describe a new lung model, allowing direct measurement of the dead space/tidal volume ratios produced by any breathing system at different fresh gas flows. The model allows a range of different patterns of spontaneous respiration to be studied. Although rebreathing is measured by capnography, the design ensures that the results are unaffected by changes in carbon dioxide inflow, or even calibration drift in the capnograph.

Concurrent utilization review and inappropriate hospital stay: evaluation of a program.

Using a crossover design, we tested the hypothesis that concurrent utilization review by a utilization officer would reduce length of stay and inappropriate bed days in a tertiary care hospital. The intervention groups included 396 consecutive patients admitted to specified services during two 1-month study periods and followed for at least 1 month or until discharge. Controls were 410 patients admitted to the same services during a preceding or subsequent month, separated by a 1-month washout period. Intervention cases had daily review of their care plan and medical condition by the utilization officer to identify existing or likely inappropriate hospital stay. The officer used interdisciplinary and interdepartmental consultation in attempting to resolve identified problems. A separate research nurse identified the controls and gathered data on the medical condition and care plan for a random 50% sample of both intervention and control cases. These data were used by a multidisciplinary panel to count and classify the reasons for inappropriate hospital days. Overall, there were no significant differences between the corresponding intervention and control groups for length of stay or proportion of inappropriate days. There was evidence of a time-related reduction in both length of stay and inappropriate days only in the subgroup of patients with a length of stay of < 15 d. As further evidence of this period effect unrelated to the intervention, length of stay had been declining for 1 of the groups of services before this study began. We concluded that concurrent utilization review, as practiced in this study, was ineffective in the short term. However, utilization review and modification of hospital processes can reduce inefficiency, as evidenced by the time-related reduction in inefficiency illustrated in our study.

Prophylactic lidocaine for postoperative coronary artery bypass patients, a double-blind, randomized trial.

This double-blind controlled study examined the frequency of ventricular arrhythmias (premature ventricular contractions (PVCs) greater than 5.min-1, bigeminy, couplets, ventricular tachycardia, and ventricular fibrillation) in coronary artery bypass graft (CABG) patients during the first 24 hr postoperatively to determine the effect of prophylactic lidocaine on reducing the frequency of ventricular arrhythmias. Patients were included in the study if they had undergone CABG only, and had not received treatment for ventricular arrhythmias before coming off cardiopulmonary bypass. A total of 83 patients were studied and were randomly allocated to 43 in the placebo control group and 40 in the lidocaine-treated group. The results showed that 67 per cent of patients in the placebo group and 33 per cent of patients in the lidocaine treated group had ventricular arrhythmias (P less than 0.005). There was also a significant reduction in ventricular fibrillation and ventricular tachycardia in the lidocaine treated group (P less than 0.01). It is recommended that a routine infusion of lidocaine, 100 mg bolus followed by 2 mg.kg-1, be given to every postoperative coronary artery bypass patient for at least the first 24 hours.