Real-life efficacy and safety of omalizumab in Portuguese patients with persistent uncontrolled asthma
M.. Pereira Barbosaa, A.. Bugalho de Almeidab, C.. Pereirac,
, C.-W. Chend, P.. Georgioue, G.. Peacheye
Corresponding author
a Serviço de Imunoalergologia, Centro Hospitalar de Lisboa Norte, Lisbon, Portugal
b Clínica Universitária de Pneumologia, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
c Novartis Farma – Produtos Farmaceuticos S.A., Avenida Professor Doutor Cavaco Silva, n.° 10E, Taguspark, 2740-255 Porto Salvo, Portugal
d Novartis Pharmaceuticals Corporation, One Health Plaza East Hanover, NJ 07936-1080, USA
e Novartis Pharmaceuticals UK Limited, Wimblehurst Road Horsham, West Sussex RH12 5AB, UK
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(a) Effect on asthma control as measured by investigator assessment; (b) effect on reduction in corticosteroid requirement. Values are for the week before specified time points." ] ] ] "textoCompleto" => "<a name="sec0005" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Introduction</span><p class="elsevierStylePara">Asthma is a chronic disease affecting approximately 300 million people worldwide and it is estimated that this number will have increased by 100 million by 2025.<a href="#bib14" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a> In Portugal, a national asthma survey showed a prevalence of current asthma in 6.8% of the population.<a href="#bib15" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a></p><p class="elsevierStylePara">Although clinical trials with combinations of inhaled corticosteroids (ICS) and β2-agonists have shown good asthma control in most patients,<a href="#bib16" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a> 10–15% have severe forms of the disease, which remain uncontrolled or poorly controlled despite receiving optimized therapies. These patients are associated with high frequency of asthma symptoms and exacerbations, impaired lung function, and poor quality of life.<a href="#bib17" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a></p><p class="elsevierStylePara">Omalizumab is a recombinant humanized monoclonal anti-immunoglobulin E (IgE) that is used in Europe for add-on therapy with CSs and long-acting β2-agonists (LABAs) for patients aged ≥6 years with severe persistent allergic asthma.<a href="#bib18" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a> Clinical trials suggest that omalizumab add-on therapy reduces asthma exacerbations, decreases oral corticosteroid (OCS) and emergency room (ER) visits as well as improves symptom severity and quality of life.<a href="#bib19" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a></p><p class="elsevierStylePara">This report focuses on the outcomes of omalizumab in combination with current therapy in Portuguese patients enrolled in a 2-year, global, post marketing registry named eXpeRience.<a href="#bib20" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a></p><a name="sec0010" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Methods</span><p class="elsevierStylePara">The eXpeRience registry was a multicenter, international, single-arm, open-label, observational study that collected data from patients receiving omalizumab for uncontrolled persistent allergic asthma, in Europe, Canada, and Asia.<a href="#bib20" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a></p><p class="elsevierStylePara">Clinical symptoms, asthma control, lung function measures, obtained forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF]), exacerbations, concomitant medication, and status of comorbidities were collected at 16 weeks and at 8, 12, 18, and 24 months after initiation. Response to treatment was evaluated at week 16 by the physician's Global Evaluation of Treatment Effectiveness (GETE) assessment 8, physical examination, and review of patient notes. Patients were rated on a 5-point scale: 1-excellent (complete control of asthma), 2-good (marked improvement), 3-moderate (discernible, but limited improvement), 4-poor (no appreciable change), and 5-worsening.<a href="#bib21" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">8</span></a> Patients with an “excellent” or “good” response were considered responders; those with “moderate”, “poor” and “worsening” response were considered non-responders. Asthma control was assessed through Asthma Control Test™ (ACT™), which is calculated from patients’ responses to five questions concerning interference with activities, shortness of breath, nocturnal symptoms, rescue medication, and self-rating of asthma control.<a href="#bib22" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">9</span></a> The patient's ACT™ score range from 5 (poorly controlled) to 25 (well-controlled). The mini-Asthma related Quality of Life Questionnaire (mini-AQLQ) assessment was used for evaluating the functional impairment in patients.<a href="#bib23" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">10</span></a> Other assessments included symptoms, use of rescue medication, lung function, asthma-related healthcare resources utilization, days of missed work, and OCS/ICS use. The annualized data on healthcare resources utilization and exacerbations at Month 12 and 24 were analyzed; 1-year history of these parameters was used for comparison. Serious adverse events (SAEs) were reported, regardless of suspected causality, within 24 h of the event's occurrence. Primary effectiveness analysis was performed on the intent-to-treat (ITT) population, which comprised all enrolled patients.</p><a name="sec0015" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStylePara">The eXpeRience study enrolled 943 patients and 62 were recruited from Portugal. Demographic and clinical characteristics of these patients are presented in <a href="#t0005" class="elsevierStyleCrossRefs">Table 1</a>. Overall, 15 patients discontinued the registry (24.2%): 4 were lost to follow-up, 1 withdrew consent, and 10 discontinued for other reasons. At the end of registry, from 55 patients with available data, omalizumab treatment was continued in 41 (66.1%).</p><p class="elsevierStylePara">Table 1. Baseline demographics and clinical characteristics.</p><a name="t0005" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Variable</td><td>Value (<span class="elsevierStyleItalic">N</span> = 62)</td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleItalic">Age group, n (%)</span></td></tr><tr align="left"><td>12–17 years</td><td>1 (1.6)</td></tr><tr align="left"><td>18–64 years</td><td>51 (82.3)</td></tr><tr align="left"><td>≥65 years</td><td>10 (16.1)</td></tr><tr align="left"><td colspan="2"> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleItalic">Age (years)</span></td></tr><tr align="left"><td>Mean (SD)</td><td>49.2 (15.0)</td></tr><tr align="left"><td colspan="2"> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleItalic">Gender, n (%)</span></td></tr><tr align="left"><td>Female</td><td>43 (69.4)</td></tr><tr align="left"><td colspan="2"> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleItalic">Race, n (%)</span></td></tr><tr align="left"><td>Caucasian</td><td>60 (96.8)</td></tr><tr align="left"><td>Black</td><td>1 (1.6)</td></tr><tr align="left"><td>Other</td><td>1 (1.6)</td></tr><tr align="left"><td colspan="2"> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleItalic">Body weight (kg)</span></td></tr><tr align="left"><td>Mean (SD)</td><td>72.5 (16.9)</td></tr><tr align="left"><td colspan="2"> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleItalic">Baseline IgE level (IU/mL)</span></td></tr><tr align="left"><td>Mean (SD)</td><td>414.3 (782.6)</td></tr><tr align="left"><td colspan="2"> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleItalic">Duration of allergic asthma (years)</span></td></tr><tr align="left"><td>Mean (SD)</td><td>24.3 (13.8)</td></tr><tr align="left"><td>Positive skin-prick test/RAST for perennial aeroallergens, n (%)</td><td>53 (85.5)</td></tr><tr align="left"><td colspan="2"> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleItalic">Specification</span><span class="elsevierStyleSup">a</span></td></tr><tr align="left"><td>Dust mites</td><td>52 (83.9)</td></tr><tr align="left"><td>Cat dander</td><td>12 (19.4)</td></tr><tr align="left"><td>Dog dander</td><td>8 (12.9)</td></tr><tr align="left"><td>Cockroaches</td><td>3 (4.8)</td></tr><tr align="left"><td>Others</td><td>5 (8.1)</td></tr><tr align="left"><td>History of allergy to seasonal aeroallergens, <span class="elsevierStyleItalic">n</span> (%)</td><td>35 (56.5)</td></tr><tr align="left"><td colspan="2"> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleItalic">Smoking history, n (%)</span></td></tr><tr align="left"><td>Never smoked</td><td>49 (79.0)</td></tr><tr align="left"><td>Ex-smoker</td><td>10 (16.1)</td></tr><tr align="left"><td>Current smoker</td><td>3 (4.8)</td></tr><tr align="left"><td colspan="2"> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleItalic">Asthma clinical symptoms, n (%)</span></td></tr><tr align="left"><td>Daytime asthma symptoms</td><td>59 (95.2)</td></tr><tr align="left"><td>Limitations of activities</td><td>55 (88.7)</td></tr><tr align="left"><td>Nocturnal symptoms/awakenings</td><td>51 (82.3)</td></tr><tr align="left"><td colspan="2"> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleItalic">Asthma control</span><span class="elsevierStyleSup">b</span> , <span class="elsevierStyleItalic">n (%)</span></td></tr><tr align="left"><td>Controlled</td><td>1 (1.6)</td></tr><tr align="left"><td>Partly controlled</td><td>10 (16.1)</td></tr><tr align="left"><td>Uncontrolled</td><td>51 (82.3)</td></tr></table><p class="elsevierStylePara">IgE, immunoglobulin E; RAST, radioallergosorbent test; SD, standard deviation.<br></br></p><p class="elsevierStylePara">a Multiple entries possible<br></br>b Investigator's assessment.<br></br></p><p class="elsevierStylePara">Maintenance therapy at baseline included OCS in 17.7% patients with mean total daily dose of 16.67 mg (prednisolone equivalent), and rescue medication in 91.9% patients in the week before.</p><p class="elsevierStylePara">The individual last time point (the time point at which the patient was last recorded as being on treatment) in majority of patients was Month 24 (72.6%) while corresponding patients’ percentages at other time-points were 1.6% (baseline), 1.6% (Week-16), 9.7% (Month-8), 8.1% (Month-12), and 6.5% (Month-18).</p><a name="sec0020" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Physician's global evaluation of treatment effectiveness</span><p class="elsevierStylePara">From patients with GETE assessment at Week 16 (<span class="elsevierStyleItalic">n</span> = 29), 62.1% were responders (excellent/good in 10.3% and 51.7%, respectively), and 37.9% were non-responders. One patient at Week 16 was identified as non-responder and stopped treatment. From patients with GETE data at any time-point (<span class="elsevierStyleItalic">n</span> = 62), 61.3% were responders (excellent/good in 8.1% and 53.2%, respectively), 32.3% non-responders, and 6.5% had no GETE assessment.</p><a name="sec0025" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Asthma symptoms and rescue medication use</span><p class="elsevierStylePara">Omalizumab reduced patients’ symptoms, activity limitations, and rescue medication use in the week before Month 12. Moreover, symptoms or rescue medication use at ≥3.5 days/week at baseline, reduced to ≤1 day/week at Month 24 (<a href="#t0010" class="elsevierStyleCrossRefs">Table 2</a>).</p><p class="elsevierStylePara">Table 2. Effect on asthma symptoms, rescue medication use, asthma control, and quality of life (ITT population).</p><a name="t0010" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td> </td><td>Baseline (<span class="elsevierStyleItalic">n</span> = 62)</td><td>Month 12 (<span class="elsevierStyleItalic">n</span> = 54)</td><td>Month 24 (<span class="elsevierStyleItalic">n</span> = 45)</td></tr><tr align="left"><td colspan="4"><span class="elsevierStyleItalic">Daytime symptoms</span></td></tr><tr align="left"><td>Patients, <span class="elsevierStyleItalic">n</span> (%) <span class="elsevierStyleSup">*</span></td><td>59 (95.2%)</td><td>21 (38.9%)</td><td>18 (40.0%)</td></tr><tr align="left"><td>Number of days, mean (SD) <span class="elsevierStyleSup">*</span></td><td>4.9 (2.2)</td><td>1.4 (2.4)</td><td>1.0 (1.8)</td></tr><tr align="left"><td>Change in number of days, mean (SD)</td><td>–</td><td>−3.3 (2.9)</td><td>−4.2 (2.6)</td></tr><tr align="left"><td colspan="4"> </td></tr><tr align="left"><td colspan="4"><span class="elsevierStyleItalic">Nocturnal symptoms or awakenings</span></td></tr><tr align="left"><td>Patients, <span class="elsevierStyleItalic">n</span> (%) <span class="elsevierStyleSup">*</span></td><td>51 (82.3%)</td><td>13 (24.1%)</td><td>7 (15.6%)</td></tr><tr align="left"><td>Number of days, mean (SD) <span class="elsevierStyleSup">*</span></td><td>3.5 (2.5)</td><td>0.7 (1.7)</td><td>0.3 (1.2)</td></tr><tr align="left"><td>Change in number of days, mean (SD)</td><td>–</td><td>−2.9 (2.8)</td><td>−3.5 (2.6)</td></tr><tr align="left"><td colspan="4"> </td></tr><tr align="left"><td colspan="4"><span class="elsevierStyleItalic">Limitations of activities</span></td></tr><tr align="left"><td>Patients, <span class="elsevierStyleItalic">n</span> (%) <span class="elsevierStyleSup">*</span></td><td>55 (88.7%)</td><td>14 (25.9%)</td><td>10 (22.2%)</td></tr><tr align="left"><td>Number of days, mean (SD) <span class="elsevierStyleSup">*</span></td><td>4.3 (2.6)</td><td>0.7 (1.6)</td><td>0.5 (1.2)</td></tr><tr align="left"><td>Change in number of days, mean (SD)</td><td>–</td><td>−3.6 (2.9)</td><td>−4.0 (2.8)</td></tr><tr align="left"><td colspan="4"> </td></tr><tr align="left"><td colspan="4"><span class="elsevierStyleItalic">Rescue medication use</span></td></tr><tr align="left"><td>Patients, <span class="elsevierStyleItalic">n</span> (%) <span class="elsevierStyleSup">*</span></td><td>57 (91.9%)</td><td>17 (31.5%)</td><td>14 (31.1%)</td></tr><tr align="left"><td>Number of days, mean (SD) <span class="elsevierStyleSup">*</span></td><td>4.3 (2.4)</td><td>1.0 (2.0)</td><td>0.7 (1.4)</td></tr><tr align="left"><td>Change in number of days, mean (SD)</td><td>–</td><td>−3.3 (2.9)</td><td>−4.0 (2.4)</td></tr><tr align="left"><td colspan="4"> </td></tr><tr align="left"><td colspan="4"><span class="elsevierStyleItalic">Corticosteroid usage</span></td></tr><tr align="left"><td>Patients on OCS, <span class="elsevierStyleItalic">n</span> (%)</td><td>11 (17.7%)</td><td>5 (9.3%)</td><td>4 (8.2%)</td></tr><tr align="left"><td>Total OCS daily dose (prednisolone equivalent mg), mean (SD) <span class="elsevierStyleSup">c</span></td><td>16.7 (17.2)</td><td>11.3 (21.7)</td><td>13.1 (24.6)</td></tr><tr align="left"><td>Patients on ICS, <span class="elsevierStyleItalic">n</span> (%)</td><td>60 (96.8%)</td><td>50 (92.6%)</td><td>40 (88.9%)</td></tr><tr align="left"><td>Total ICS daily dose (beclomethasone dipropionate equivalent μg), mean (SD) <span class="elsevierStyleSup">d</span></td><td>1497.5 (766.5)</td><td>1494.3 (765.0)</td><td>1351.1 (846.8)</td></tr><tr align="left"><td colspan="4"> </td></tr><tr align="left"><td colspan="4"><span class="elsevierStyleItalic">Asthma control, ACT</span>™ <span class="elsevierStyleItalic">score</span></td></tr><tr align="left"><td>≥2 point improvement, <span class="elsevierStyleItalic">n</span> (%) <span class="elsevierStyleSup">a</span></td><td>–</td><td>31 (88.6%)</td><td>23 (88.5%)</td></tr><tr align="left"><td>Transition from uncontrolled asthma (≤19 points) to controlled asthma (>19 points), <span class="elsevierStyleItalic">n</span> (%) <span class="elsevierStyleSup">a</span></td><td>–</td><td>22 (62.9%)</td><td>18 (69.2%)</td></tr><tr align="left"><td colspan="4"> </td></tr><tr align="left"><td colspan="4"><span class="elsevierStyleItalic">Mini-AQLQ score</span></td></tr><tr align="left"><td>Mean (SD) <span class="elsevierStyleSup">e</span></td><td>3.1 (1.1)</td><td>5.1 (1.5)</td><td>5.8 (1.3)</td></tr><tr align="left"><td>Change in mini-AQLQ, mean (SD) <span class="elsevierStyleSup">b</span></td><td>–</td><td>+2.1 (2.0)</td><td>+2.7 (1.8)</td></tr><tr align="left"><td>≥0.5 point improvement, <span class="elsevierStyleItalic">n</span> (%) <span class="elsevierStyleSup">b</span></td><td>–</td><td>15 (75.0%)</td><td>12 (92.3%)</td></tr></table><p class="elsevierStylePara">SD, standard deviation.<br></br></p><p class="elsevierStylePara">* Data are presented for the presence of these outcomes in the week before baseline, Month 12, and Month 24.<br></br>a <span class="elsevierStyleItalic">n</span> = 35, 26 at Months 12.<br></br>b <span class="elsevierStyleItalic">n</span> = 20, 13 at Months 24.<br></br>c <span class="elsevierStyleItalic">n</span> = 6, 5, 4 at baseline.<br></br>d <span class="elsevierStyleItalic">n</span> = 61, 53, 45 at Months 12.<br></br>e <span class="elsevierStyleItalic">n</span> = 28, 22, 13 at Months 24.<br></br></p><a name="sec0030" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Lung function</span><p class="elsevierStylePara">Mean FEV1% predicted improved by 8.6% (18.4%) at Month 12 (<span class="elsevierStyleItalic">n</span> = 27) and 9.6% (16.6%) at Month 24 (<span class="elsevierStyleItalic">n</span> = 27). PEF improved from baseline by mean of 22.0 (82.5) L/min at Month 12 (<span class="elsevierStyleItalic">n</span> = 28) and 45.4 (66.7) L/min at Month 24 (<span class="elsevierStyleItalic">n</span> = 23).</p><a name="sec0035" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Asthma control and quality of life</span><p class="elsevierStylePara">A higher percentage of patients had controlled or partly controlled asthma in the week before Months 12 and 24 than reported at baseline (<a href="#f0005" class="elsevierStyleCrossRefs">Figure 1</a>a). Omalizumab treatment improved asthma control as measured by the mean ACT™ score at all time points, with improvements versus baseline (<span class="elsevierStyleItalic">n</span> = 45) by 7.7 (5.1) at Month 12 (<span class="elsevierStyleItalic">n</span> = 35) and 7.0 (4.1) at Month 24 (<span class="elsevierStyleItalic">n</span> = 26). Over 60% of the patients were observed to transition from uncontrolled asthma at baseline to controlled asthma, and over 80% of patients showed improvements in ACT™ score by ≥2 points at Month 12 and 24. Similarly, quality of life with respect to the mini-AQLQ score and proportion of patients with clinically improvements in mini-AQLQ score at Months 12 and 24 compared with baseline were improved (<a href="#t0010" class="elsevierStyleCrossRefs">Table 2</a>).</p><a name="f0005" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"><img src="320v21n03-" alt="Analysis over the 24 months of treatment period. (a) Effect on asthma control as measured by investigator assessment; (b) effect on reduction in corticosteroid requirement. Values are for the week before specified time points."></img></p><p class="elsevierStylePara">Figure 1. Analysis over the 24 months of treatment period. (a) Effect on asthma control as measured by investigator assessment; (b) effect on reduction in corticosteroid requirement. Values are for the week before specified time points.</p><a name="sec0040" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Exacerbations</span><p class="elsevierStylePara">The mean numbers of clinically significant and severe exacerbations reduced at Months 12 and 24 compared with baseline. Moreover, the number of patients with no clinically significant and no severe clinically significant exacerbations increased at Months 12 and 24 (66.1%, 20.4% and 11.1% of patients with severe exacerbations at baseline, Months 12 and 24, respectively).</p><a name="sec0045" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Healthcare utilization use</span><p class="elsevierStylePara">Asthma-related medical healthcare use and missed days of work due to asthma at Months 12 and 24 were significantly reduced (<a href="#t0010" class="elsevierStyleCrossRefs">Table 2</a>).</p><a name="sec0050" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Corticosteroid use</span><p class="elsevierStylePara">At baseline, higher numbers of patients were on OCS/ICS maintenance treatments; this proportion reduced at Month 12 and 24 along with a corresponding increase in patients who showed reduction or discontinuation of OCS/ICS use (<a href="#f0005" class="elsevierStyleCrossRefs">Figure 1</a>b). Of the patients on OCS/ICS maintenance treatments, the mean total daily dose went down over time from baseline to Month 24.</p><a name="sec0055" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Serious adverse events</span><p class="elsevierStylePara">Overall, two SAEs were reported in two patients. The tracheobronchitis incidence was not suspected to be study-related, whereas pulmonary embolism was suspected to be study-related leading to treatment withdrawal.</p><a name="sec0060" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Discussion</span><p class="elsevierStylePara">In Portugal, asthmatic patients are managed under Portuguese Guidelines on control of asthma adapted from GINA guidelines.<a href="#bib18" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a> Both reports recommend adjunctive therapy with anti-IgE such as omalizumab, for patients whose symptoms are not controlled despite combination therapy including high doses of ICSs and LABAs. This report evaluated efficacy and safety of omalizumab treatment in Portuguese patients with uncontrolled asthma enrolled in the eXpeRience registry.<a href="#bib20" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a></p><p class="elsevierStylePara">The majority of patients in Portugal (62.1%) were rated as excellent/good responders. This finding is consistent with the global registry, where 69.9% of patients were responders.<a href="#bib20" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a></p><p class="elsevierStylePara">Portuguese patients treated with omalizumab reduced daytime/nocturnal symptoms, activity limitations and rescue medication usage. Furthermore, there were reductions in the clinically significant and severe clinically significant exacerbations similar to those observed in the global registry and other real-life studies in Portugal.<a href="#bib20" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a><span class="elsevierStyleSup">, </span><a href="#bib27" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">11</span></a></p><p class="elsevierStylePara">Clinically meaningful improvements in important outcomes (ACT™ and mini-AQLQ) together with over 90% of patients showing ≥0.5 score increase at Month 24 were also registered. These findings are comparable with another Portuguese study where there has been progress for ACT™.<a href="#bib28" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">12</span></a> Moreover, the 8.6% and 9.6% improvements in the FEV1% predicted at Months 12 and 24 observed in this analysis are similar to those observed in another Portuguese study with omalizumab.<a href="#bib26" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">13</span></a></p><p class="elsevierStylePara">In this study, the number of patients on OCS maintenance treatment reduced from 11 to 4 patients at Month 24 accompanied with a dose reduction from 16.7 mg (prednisolone equivalent) to 13.1 mg.</p><p class="elsevierStylePara">After omalizumab treatment, asthma-related healthcare resource utilization and days of missed work due to asthma were reduced, according to the global registry.<a href="#bib20" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a> Efficacy outcomes were consistent with this study confirming omalizumab efficacy in treatment of uncontrolled severe allergic asthma.<a href="#bib19" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a> In Portugal the percentage of patients with SAEs (3.2%) was lower when compared with the eXpeRience registry (6.9%).<a href="#bib20" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a></p><p class="elsevierStylePara">The major limitation of this study is the low number of patients, along with other limitations of the overall eXpeRience registry discussed previously.<a href="#bib20" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a> A remarkable issue is that the results observed in Portugal were comparable with the observations from the eXpeRience population. Hence, the benefits of the omalizumab therapy observed in Portugal could be further supported by the global study that included comparatively larger patient numbers.<a href="#bib20" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a></p><p class="elsevierStylePara">In conclusion, Portuguese results are consistent with the global eXpeRience registry and are supportive of the existing evidence that omalizumab therapy improves lung function, reduces asthma symptoms, exacerbations, healthcare utilization, and improves ACT™ score and quality of life in these patients.</p><a name="sec0065" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Ethical disclosures</span><a name="sec0070" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Protection of human and animal subjects’</span><p class="elsevierStylePara">The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association (Declaration of Helsinki).</p><a name="sec0075" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Confidentiality of data</span><p class="elsevierStylePara">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p><a name="sec0080" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p class="elsevierStylePara">The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.</p><a name="sec0085" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p class="elsevierStylePara">Manuel Pereira Barbosa has participated as consultant in advisory boards and has been involved in clinical trials sponsored by Novartis.</p><p class="elsevierStylePara">Antonio Bugalho de Almeida has participated as consultant in advisory boards and as speaker in meetings organized by Boehringer Ingelheim, GlaxoSmithKline, Novartis Farma and Pfizer. Antonio Bugalho de Almeida has also been involved in clinical trials sponsored by Boehringer Ingelheim and Novartis Farma.</p><p class="elsevierStylePara">Catarina Pereira, Chien-Wei Chen, Panayiotis P. Georgiou, Guy Peachey are employees of Novartis.</p><p class="elsevierStylePara">Acknowledgements</p><p class="elsevierStylePara">The eXpeRience study group is also composed of the following investigators: Luis Taborda and La Salete Valente, Centro Hospitalar da Cova da Beira; Graça Castel Branco and João Fonseca, Hospital de São João, José Ferreira and Aurora Carvalho, Centro Hospitalar de Vila Nova de Gaia/Espinho, Ulisses Brito, Hospital Central de Faro, Gil Duarte and Margarida Trindade, Centro Hospitalar Lisboa Norte, Hospital Pulido Valente, Fernando Nogueira, Centro Hospitalar de Lisboa Ocidental, Fernando Rodrigues, Hospital Fernando Fonseca, Joaquim Saraiva Cruz, Hospital de Santarém, António Domingos, Centro Hospitalar de Torres Vedras, Pedro da Costa and Paulo Santana, Unidade Local de Saúde do Norte Alentejano, Luis Ferreira, Hospital de Sousa Martins, Luisa Melão, Hospital do Espírito Santo, Laura Simão, Centro Hospitalar do Tâmega e Sousa, Jorge Roldão Vieira, Hospital Garcia de Orta, Jorge Pires, Ana Arrobas and Carlos Mendonça, Centro Hospitalar de Coimbra. The authors would like to thank Swathi Malla, Novartis, for providing the medical writing support in the development of this report. The writing support was funded by Novartis Farma – Produtos, Portugal. The registry was designed and sponsored by Novartis Pharma AG.</p><p class="elsevierStylePara">Received 24 March 2014 <br></br>Accepted 19 July 2014 </p><p class="elsevierStylePara">Corresponding author. catarina.pereira@novartis.com</p>" "pdfFichero" => "320v21n03a90418843pdf001.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec640988" "palabras" => array:6 [ 0 => "Omalizumab" 1 => "Allergic asthma" 2 => "Anti-immunoglobulin E" 3 => "Asthma control" 4 => "Exacerbations" 5 => "Observational study" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Introduction</span><br/><p class="elsevierStylePara">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.</p><span class="elsevierStyleSectionTitle">Methods</span><br/><p class="elsevierStylePara">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.</p><span class="elsevierStyleSectionTitle">Results</span><br/><p class="elsevierStylePara">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 [<span class="elsevierStyleItalic">n</span> = 35]; +2.1 [<span class="elsevierStyleItalic">n</span> = 20], respectively) and 24 (mean change: +7.0 [<span class="elsevierStyleItalic">n</span> = 26]; +2.7 [<span class="elsevierStyleItalic">n</span> = 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 (<span class="elsevierStyleItalic">n</span> = 62) to 50% at Month 12 (<span class="elsevierStyleItalic">n</span> = 54) and 60% at Month 24 (<span class="elsevierStyleItalic">n</span> = 45).</p><span class="elsevierStyleSectionTitle">Conclusion</span><br/><p class="elsevierStylePara">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.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "descripcion" => array:1 [ "en" => "Analysis over the 24 months of treatment period. (a) Effect on asthma control as measured by investigator assessment; (b) effect on reduction in corticosteroid requirement. Values are for the week before specified time points." ] ] 1 => array:6 [ "identificador" => "fig2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "descripcion" => array:1 [ "en" => "Analysis over the 24 months of treatment period. (a) Effect on asthma control as measured by investigator assessment; (b) effect on reduction in corticosteroid requirement. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 5 | 12 |
| 2024 October | 62 | 32 | 94 |
| 2024 September | 64 | 25 | 89 |
| 2024 August | 69 | 29 | 98 |
| 2024 July | 51 | 35 | 86 |
| 2024 June | 61 | 23 | 84 |
| 2024 May | 45 | 31 | 76 |
| 2024 April | 57 | 26 | 83 |
| 2024 March | 60 | 31 | 91 |
| 2024 February | 48 | 24 | 72 |
| 2024 January | 41 | 24 | 65 |
| 2023 December | 34 | 29 | 63 |
| 2023 November | 46 | 30 | 76 |
| 2023 October | 42 | 43 | 85 |
| 2023 September | 31 | 29 | 60 |
| 2023 August | 40 | 22 | 62 |
| 2023 July | 40 | 27 | 67 |
| 2023 June | 38 | 16 | 54 |
| 2023 May | 64 | 23 | 87 |
| 2023 April | 40 | 14 | 54 |
| 2023 March | 80 | 22 | 102 |
| 2023 February | 58 | 21 | 79 |
| 2023 January | 47 | 22 | 69 |
| 2022 December | 68 | 20 | 88 |
| 2022 November | 92 | 39 | 131 |
| 2022 October | 55 | 43 | 98 |
| 2022 September | 34 | 27 | 61 |
| 2022 August | 51 | 35 | 86 |
| 2022 July | 48 | 50 | 98 |
| 2022 June | 40 | 35 | 75 |
| 2022 May | 47 | 35 | 82 |
| 2022 April | 32 | 32 | 64 |
| 2022 March | 43 | 45 | 88 |
| 2022 February | 47 | 39 | 86 |
| 2022 January | 31 | 35 | 66 |
| 2021 December | 38 | 33 | 71 |
| 2021 November | 36 | 43 | 79 |
| 2021 October | 43 | 41 | 84 |
| 2021 September | 31 | 34 | 65 |
| 2021 August | 29 | 25 | 54 |
| 2021 July | 27 | 13 | 40 |
| 2021 June | 26 | 25 | 51 |
| 2021 May | 33 | 26 | 59 |
| 2021 April | 100 | 55 | 155 |
| 2021 March | 73 | 18 | 91 |
| 2021 February | 53 | 19 | 72 |
| 2021 January | 34 | 11 | 45 |
| 2020 December | 32 | 9 | 41 |
| 2020 November | 39 | 23 | 62 |
| 2020 October | 39 | 16 | 55 |
| 2020 September | 59 | 28 | 87 |
| 2020 August | 79 | 24 | 103 |
| 2020 July | 100 | 22 | 122 |
| 2020 June | 94 | 14 | 108 |
| 2020 May | 100 | 22 | 122 |
| 2020 April | 85 | 5 | 90 |
| 2020 March | 84 | 9 | 93 |
| 2020 February | 75 | 26 | 101 |
| 2020 January | 89 | 19 | 108 |
| 2019 December | 93 | 14 | 107 |
| 2019 November | 86 | 14 | 100 |
| 2019 October | 88 | 25 | 113 |
| 2019 September | 77 | 28 | 105 |
| 2019 August | 107 | 8 | 115 |
| 2019 July | 137 | 19 | 156 |
| 2019 June | 143 | 19 | 162 |
| 2019 May | 121 | 8 | 129 |
| 2019 April | 118 | 32 | 150 |
| 2019 March | 187 | 16 | 203 |
| 2019 February | 187 | 6 | 193 |
| 2019 January | 167 | 26 | 193 |
| 2018 December | 81 | 4 | 85 |
| 2018 November | 49 | 0 | 49 |
| 2018 October | 51 | 11 | 62 |
| 2018 September | 19 | 12 | 31 |
| 2018 August | 43 | 23 | 66 |
| 2018 July | 31 | 16 | 47 |
| 2018 June | 33 | 17 | 50 |
| 2018 May | 47 | 25 | 72 |
| 2018 April | 44 | 18 | 62 |
| 2018 March | 54 | 19 | 73 |
| 2018 February | 15 | 14 | 29 |
| 2018 January | 18 | 14 | 32 |
| 2017 December | 21 | 32 | 53 |
| 2017 November | 18 | 19 | 37 |
| 2017 October | 17 | 18 | 35 |
| 2017 September | 21 | 16 | 37 |
| 2017 August | 24 | 8 | 32 |
| 2017 July | 18 | 6 | 24 |
| 2017 June | 25 | 21 | 46 |
| 2017 May | 24 | 23 | 47 |
| 2017 April | 11 | 7 | 18 |
| 2017 March | 27 | 11 | 38 |
| 2017 February | 9 | 11 | 20 |
| 2017 January | 12 | 7 | 19 |
| 2016 December | 10 | 9 | 19 |
| 2016 November | 8 | 3 | 11 |
| 2016 October | 5 | 3 | 8 |
| 2016 September | 1 | 0 | 1 |
| 2016 August | 6 | 4 | 10 |
| 2016 July | 4 | 8 | 12 |
| 2016 June | 0 | 5 | 5 |
| 2016 May | 1 | 6 | 7 |
| 2016 April | 19 | 1 | 20 |
| 2016 March | 47 | 17 | 64 |
| 2016 February | 41 | 26 | 67 |
| 2016 January | 22 | 13 | 35 |
| 2015 December | 26 | 12 | 38 |
| 2015 November | 18 | 17 | 35 |
| 2015 October | 26 | 31 | 57 |
| 2015 September | 51 | 21 | 72 |
| 2015 August | 55 | 40 | 95 |
| 2015 July | 54 | 28 | 82 |
| 2015 June | 69 | 36 | 105 |
| 2015 May | 196 | 105 | 301 |
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