Letter to the editor
Mepolizumab for severe eosinophilic asthma – A one-year real life Portuguese study
R Brás1,
, M Paulino1, C Varandas, C Coutinho, MI Silva, R Limão, C Costa, E Alonso, E Pedro, A Mendes
Corresponding author
ritasabras@gmail.com
Corresponding author at: Immunoallergology Department, Hospital de Santa Maria – Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
Corresponding author at: Immunoallergology Department, Hospital de Santa Maria – Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
Immunoallergology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
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We aimed to assess its effectiveness and safety in Portuguese severe eosinophilic asthmatic patients.</p><p id="para0004" class="elsevierStylePara elsevierViewall">We conducted a single-center, observational, retrospective study, involving severe asthmatic patients under mepolizumab 100 mg subcutaneous, every 4 weeks for ≥12 months, from July 2017 to August 2020. Eligibility for treatment included a blood eosinophil count (BEC) <span class="elsevierStyleBold">≥</span>150/mm<span class="elsevierStyleSup">3</span> at baseline or <span class="elsevierStyleBold">≥</span>300/mm<span class="elsevierStyleSup">3</span> during the previous year. Demographic and clinical data were collected from the Portuguese Severe Asthma Registry (RAG) database. A written informed consent was obtained. BEC, Forced Expiratory Volume in one second (FEV1), exacerbation rate and oral corticosteroid (OCS) intake, as well as patient-reported outcomes (PROs) Asthma Control Test (ACT), Control of Allergic Rhinitis and Asthma Test (CARAT) and Mini Asthma Quality of Life Questionnaire (Mini-AQLQ) were accessed. Adverse events were documented. For statistical analyses (IBM-SPSS software, v25.0), t-independent and Mann-Whitney tests were used to compare parametric and non-parametric independent samples, respectively, while paired-t and Wilcoxon tests were employed to evaluate differences between intervals within the same variable, as appropriate. <span class="elsevierStyleItalic">P</span>-values <0.05 were considered statistically significant.</p><p id="para0005" class="elsevierStylePara elsevierViewall">A total of 20 patients were enrolled in the study, mean age 54.0 ± 17.0 years [16–77 years], 13 were female (65%). Asthma diagnosis had been made, on average, 20 years before and severe asthma 10 years before. Mean BMI was 27.3 ± 5.4 Kg/m<span class="elsevierStyleSup">2</span> [19.5–38.3 Kg/m<span class="elsevierStyleSup">2</span>], with six patients (30%) obese (BMI≥30 Kg/m<span class="elsevierStyleSup">2</span>). Total serum IgE (median 274 kU/L, IQR 417.5 kU/L) was ≥100 kU/L in 16 patients (80%), with 10 patients (50%) showing positive skin prick testing (SPT). Rhinitis (<span class="elsevierStyleItalic">N</span> = 15, 75%), rhinosinusitis (<span class="elsevierStyleItalic">N</span> = 8, 40%) and nasal polyposis (NP) (<span class="elsevierStyleItalic">N</span> = 8, 40%) were the most common comorbidities (<a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>).</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia><p id="para0006" class="elsevierStylePara elsevierViewall">Regarding mepolizumab's efficacy (<a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>A), BEC significantly decreased from a mean of 753.2 ± 429/mm<span class="elsevierStyleSup">3</span> to 101.7 ± 102/mm<span class="elsevierStyleSup">3</span> (−86.5%, <span class="elsevierStyleItalic">p</span> < 0.001), as well as annual exacerbation rate (mean reduction 2.5/year, <span class="elsevierStyleItalic">p</span> < 0.001) and daily OCS intake with only two patients remaining under OCS after 12 months of mepolizumab (prednisolone 5 mg at alternate days, mean reduction 9.17 mg/day). There were no hospitalizations. Considering FEV1, only a slight improvement was observed (mean baseline of 2.1 ± 0.9 L to 2.2 ± 0.8 L, <span class="elsevierStyleItalic">p</span> > 0.05).</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><p id="para0007" class="elsevierStylePara elsevierViewall">Concerning PROs (<a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>A), statistically significant changes were observed in ACT (mean ∆-ACT 5.4 points, <span class="elsevierStyleItalic">p</span> < 0.001), with 16 patients (80%) presenting ≥20 points after 12 months of treatment, and mini-AQLQ (mean ∆-mini-AQLQ 1.3 points, <span class="elsevierStyleItalic">p</span> 0.02), while CARAT improvement did not reach statistical significance. Worth noting, 12-month mean upper airways score was lower compared with mean lower airways score (6/12 vs 12/18 points). NP was not monitored, although we did not find significant differences in ACT or exacerbations in these patients (<span class="elsevierStyleItalic">p</span> > 0.05).</p><p id="para0008" class="elsevierStylePara elsevierViewall">A sub-analysis was attempted comparing changes in BEC, ACT and exacerbation rate after 12 months of treatment in patients with baseline BEC≥500/mm<span class="elsevierStyleSup">3</span> vs <500/mm<span class="elsevierStyleSup">3</span>, BMI≥30 Kg/m<span class="elsevierStyleSup">2</span> vs <30 Kg/m<span class="elsevierStyleSup">2</span>, positive vs negative SPT, total serum IgE≥100 kU/L vs <100 kU/L (<a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>B). There was a statistically significant difference (<span class="elsevierStyleItalic">p</span> < 0.05) between the groups of BEC≥500/mm<span class="elsevierStyleSup">3</span> vs <500/mm<span class="elsevierStyleSup">3</span> regarding changes in ACT.</p><p id="para0009" class="elsevierStylePara elsevierViewall">Mepolizumab was well tolerated. Adverse events reported included myalgias in three patients, reverted with administration of magnesium, and persistent abdominal pain in one patient whose biological therapy was switched to another anti-IL-5.</p><p id="para0010" class="elsevierStylePara elsevierViewall">Our study confirms mepolizumab's efficacy and safety, being the first study in a Portuguese cohort with severe eosinophilic asthma. These effects were similar in allergic and non-allergic patients, irrespective of total IgE serum concentrations. Patients with higher baseline BEC reported better symptom control, although annual exacerbation rate did not differ significantly.</p><p id="para0011" class="elsevierStylePara elsevierViewall">We report a 76% improvement in annual exacerbation rate and a 92% reduction in daily OCS intake, which is higher than the reports of MENSA and SIRIUS clinical trials,<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> but in line with other real-life studies.<a class="elsevierStyleCrossRefs" href="#bib0003"><span class="elsevierStyleSup">3–5</span></a> Similarly, a significant improvement in ACT score was documented, reaching not only statistical but clinical significance with ∆-ACT ≥3 points and 80% of patients adequately controlled (ACT≥20), as well as in quality of life. CARAT score did not reach statistical significance probably due to a less expressive improvement in nasal symptoms.</p><p id="para0012" class="elsevierStylePara elsevierViewall">Despite real-life studies<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> generally showing better results in FEV1 changes, ours failed to show significant improvement, probably due to the lack of reversibility in some patients. On the other hand, mepolizumab significantly reduced BEC in our cohort, suggesting a decrease in inflammation, with better results in patients with higher baseline values. However, larger real-life studies did not find statistically significant results.<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a></p><p id="para0013" class="elsevierStylePara elsevierViewall">Regarding positivity in SPT or baseline total IgE, our results are in line with others previously reported,<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> suggesting mepolizumab is effective in both allergic and non-allergic patients. Moreover, obese patients did not present significant differences in response to mepolizumab treatment compared to non-obese.</p><p id="para0014" class="elsevierStylePara elsevierViewall">The limitations of our study include the reduced sample, limiting extrapolation of results, and its retrospective design, which could weaken our findings. However, it is the authors’ opinion that it has an important added value in providing the first real world evidence about the effect of mepolizumab in a cohort of Portuguese severe eosinophilic asthmatic patients.</p><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Funding</span><p id="para0015" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0001" "titulo" => "Funding" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-03-24" "fechaAceptado" => "2021-05-24" "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="notep0001">Both authors contributed equally to the work.</p>" "identificador" => "fn1" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0001" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3709 "Ancho" => 3061 "Tamanyo" => 468401 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A:</span> Changes in blood eosinophil count (a), exacerbation rate (b), FEV1 (Forced Expiratory Volume in one second) (c), ACT (Asthma Control Test) score (d), CARAT (Control of Allergic Rhinitis and Asthma Test) score (e) and mini-AQLQ (Mini Asthma Quality of Life Questionnaire) score (f) after 12 months of mepolizumab. <span class="elsevierStyleBold">B:</span> Comparison of BEC (blood eosinophil count) reduction, ACT improvement and exacerbation rate reduction after 12 months of mepolizumab between different groups (baseline BEC≥500/mm<span class="elsevierStyleSup">3</span> vs <500/mm<span class="elsevierStyleSup">3</span>, BMI (Body Mass Index) ≥30 Kg/m<span class="elsevierStyleSup">2</span> vs <30 Kg/m<span class="elsevierStyleSup">2</span>, positive vs negative SPT (Skin Prick Testing), total serum IgE≥100 kU/L vs <100 kU/L).</p>" ] ] 1 => array:8 [ "identificador" => "tbl0001" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0002" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Data presented as n(%), mean±SD and median(IQR) as appropriate. BMI, body mass index; FEV1, forced expiratory volume in one second; GERD, gastroesophageal reflux disease; ICS+LABA, inhaled corticosteroid + long-acting beta-agonist; LAMA, long-acting muscarinic antagonist; LTRA, leukotriene receptor antagonist; NSAID, non-steroidal anti-inflammatory drugs; OCS, oral corticosteroids.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline characteristic \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0003"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Total number of patients \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0004"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0005"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Age, years \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0006"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">54.0 ± 17.0[16–77] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0007"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Sex, male/female \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7(35)/13(65) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0009"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">BMI, Kg/m<span class="elsevierStyleSup">2</span> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">27.3 ± 5.4[19.5–38.3] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0011"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Smoking status \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0013"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">–</span><p id="para0017" class="elsevierStylePara elsevierViewall">Non-smoker</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">18(90) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0015"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0002"><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">–</span><p id="para0018" class="elsevierStylePara elsevierViewall">Ex-smoker</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2(10) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0017"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0003"><li class="elsevierStyleListItem" id="celistitem0003"><span class="elsevierStyleLabel">–</span><p id="para0019" class="elsevierStylePara elsevierViewall">Current smoker</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0(0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0019"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Age of Asthma onset, years \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">32.0 ± 16.0[6–62] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Age of Severe Asthma diagnosis, years \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">44.0 ± 15.0[13–70] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0023"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Total serum IgE, kU/L \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">274 (417.5)[8–1359] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0025"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">FEV1, L \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2.1 ± 0.9[0.9–3.6] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0027"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Positive skin prick test \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10(50) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0029"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0004"><li class="elsevierStyleListItem" id="celistitem0004"><span class="elsevierStyleLabel">–</span><p id="para0020" class="elsevierStylePara elsevierViewall">House dust mite</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0031"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0005"><li class="elsevierStyleListItem" id="celistitem0005"><span class="elsevierStyleLabel">–</span><p id="para0021" class="elsevierStylePara elsevierViewall">Pollens</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0033"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0006"><li class="elsevierStyleListItem" id="celistitem0006"><span class="elsevierStyleLabel">–</span><p id="para0022" class="elsevierStylePara elsevierViewall">Poly-sensitized</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0035"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Comorbidities: \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0037"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0007"><li class="elsevierStyleListItem" id="celistitem0007"><span class="elsevierStyleLabel">–</span><p id="para0023" class="elsevierStylePara elsevierViewall">Rhinitis</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15(75) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0039"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0008"><li class="elsevierStyleListItem" id="celistitem0008"><span class="elsevierStyleLabel">–</span><p id="para0024" class="elsevierStylePara elsevierViewall">Rhinosinusitis</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8(40) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0041"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0009"><li class="elsevierStyleListItem" id="celistitem0009"><span class="elsevierStyleLabel">–</span><p id="para0025" class="elsevierStylePara elsevierViewall">Nasal Polyposis</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8(40) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0043"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0010"><li class="elsevierStyleListItem" id="celistitem0010"><span class="elsevierStyleLabel">–</span><p id="para0026" class="elsevierStylePara elsevierViewall">NSAID hypersensitivity</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">5(25) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0045"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0011"><li class="elsevierStyleListItem" id="celistitem0011"><span class="elsevierStyleLabel">–</span><p id="para0027" class="elsevierStylePara elsevierViewall">GERD</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2(10) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0047"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0012"><li class="elsevierStyleListItem" id="celistitem0012"><span class="elsevierStyleLabel">–</span><p id="para0028" class="elsevierStylePara elsevierViewall">Bronchiectasis</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1(5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0049"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Chronic therapy: \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0051"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0013"><li class="elsevierStyleListItem" id="celistitem0013"><span class="elsevierStyleLabel">–</span><p id="para0029" class="elsevierStylePara elsevierViewall">ICS+LABA</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20(100) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0053"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0014"><li class="elsevierStyleListItem" id="celistitem0014"><span class="elsevierStyleLabel">–</span><p id="para0030" class="elsevierStylePara elsevierViewall">LAMA</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20(100) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0055"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0015"><li class="elsevierStyleListItem" id="celistitem0015"><span class="elsevierStyleLabel">–</span><p id="para0031" class="elsevierStylePara elsevierViewall">LTRA</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20(100) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0057"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0016"><li class="elsevierStyleListItem" id="celistitem0016"><span class="elsevierStyleLabel">–</span><p id="para0032" class="elsevierStylePara elsevierViewall">Methylxanthines</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">5(25) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0059"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><ul class="elsevierStyleList" id="celist0017"><li class="elsevierStyleListItem" id="celistitem0017"><span class="elsevierStyleLabel">–</span><p id="para0033" class="elsevierStylePara elsevierViewall">OCS</p></li></ul> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">6 (30) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0061"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Previous Omalizumab \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">5(25) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2739622.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Baseline demographic and clinical characterization.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec1" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0001" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mepolizumab treatment in patients with severe eosinophilic asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.G. 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Sanchez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/cea.13601" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2020" "volumen" => "50" "numero" => "6" "paginaInicial" => "687" "paginaFinal" => "695" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0006" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Real-life evaluation of mepolizumab efficacy in patients with severe eosinophilic asthma, according to atopic trait and allergic phenotype" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Pelaia" 1 => "C. Crimi" 2 => "G. Pelaia" 3 => "S. Nolasco" 4 => "R. Campisi" 5 => "E. Heffler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/cea.13613" "Revista" => array:7 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2020" "volumen" => "50" "numero" => "7" "paginaInicial" => "780" "paginaFinal" => "788" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32347992" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0007" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The importance of being not significant: blood eosinophils and clinical responses do not correlate in severe asthma patients treated with mepolizumab in real life" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Bagnasco" 1 => "A. Massolo" 2 => "M. Bonavia" 3 => "L. Brussino" 4 => "C. Bucca" 5 => "M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 4 | 10 |
| 2024 October | 41 | 27 | 68 |
| 2024 September | 42 | 23 | 65 |
| 2024 August | 43 | 29 | 72 |
| 2024 July | 44 | 33 | 77 |
| 2024 June | 41 | 26 | 67 |
| 2024 May | 40 | 31 | 71 |
| 2024 April | 35 | 34 | 69 |
| 2024 March | 54 | 26 | 80 |
| 2024 February | 57 | 25 | 82 |
| 2024 January | 30 | 21 | 51 |
| 2023 December | 23 | 25 | 48 |
| 2023 November | 47 | 44 | 91 |
| 2023 October | 39 | 30 | 69 |
| 2023 September | 32 | 37 | 69 |
| 2023 August | 35 | 18 | 53 |
| 2023 July | 27 | 31 | 58 |
| 2023 June | 30 | 17 | 47 |
| 2023 May | 36 | 35 | 71 |
| 2023 April | 21 | 40 | 61 |
| 2023 March | 39 | 32 | 71 |
| 2023 February | 23 | 21 | 44 |
| 2023 January | 19 | 21 | 40 |
| 2022 December | 39 | 39 | 78 |
| 2022 November | 46 | 37 | 83 |
| 2022 October | 67 | 39 | 106 |
| 2022 September | 44 | 41 | 85 |
| 2022 August | 43 | 41 | 84 |
| 2022 July | 45 | 50 | 95 |
| 2022 June | 40 | 43 | 83 |
| 2022 May | 42 | 39 | 81 |
| 2022 April | 43 | 48 | 91 |
| 2022 March | 34 | 54 | 88 |
| 2022 February | 42 | 49 | 91 |
| 2022 January | 60 | 51 | 111 |
| 2021 December | 102 | 66 | 168 |
| 2021 November | 181 | 82 | 263 |
| 2021 October | 26 | 51 | 77 |
| 2021 September | 18 | 39 | 57 |
| 2021 August | 23 | 51 | 74 |
| 2021 July | 62 | 49 | 111 |
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