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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Recently&#44; monoclonal antibodies have been used for the treatment of various severe diseases&#44; such as rheumatoid arthritis&#44; ankylosing spondylitis&#44; multiple sclerosis&#44; cancer infections among others&#46; They have immunomodulatory effects&#44; are prepared against specific cytokines&#44; inhibit specific enzymes or signaling molecules&#46; Today&#44; more than 60 monoclonal antibodies have been approved for clinical therapeutic use&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Monoclonal antibodies are generally well tolerated&#44; but those that suppress the immune system may reactivate latent infections&#44; such as tuberculosis or hepatitis B&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In pulmonary diseases&#44; monoclonal antibodies have been tested primarily in asthma with significant results&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The anti-IgE and the anti-interleukin-5 &#40;IL-5&#41; antibodies are now part of the regular treatment of severe asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The anti-IL-5 antibodies had been shown to be very effective in severe eosinophilic asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">These findings led to the hypothesis that these antibodies could be also effective in the sub-group of COPD patients with high eosinophilic counts in the blood&#46; Thereafter&#44; two monoclonal antibodies &#40;Mepolizumab&#44; Benralizumab&#41;&#44; both against IL-5 have been tested in eosinophilic COPD patients&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In 2017 Pavord et al&#46; performed two randomized&#44; placebo-controlled&#44; double-blind&#44; parallel-group trials of Mepolizumab &#40;METREY and METREO&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> One hundred mg in METREX and 100 or 300mg in METREO of Mepolizumab were given to an eosinophilic phenotype of COPD patients &#40;&#62;150 per cubic millimeter&#41;&#46; The primary end point in both trials was the annual rate of moderate or severe exacerbations&#46; It was concluded that Mepolizumab at a dose of 100<span class="elsevierStyleHsp" style=""></span>mg was associated with lower annual rate of exacerbations than placebo&#46; In addition it was shown that the greatest effect was found among patients with higher blood eosinophilic counts&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In 2019 Fernadez Romero et al&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> reviewed the literature of the clinical efficacy&#44; safety and side effects of Mepolizumab in the management of eosinophilic COPD patients and concluded that out of the three trials only one study showed significant effect on the annual rate of exacerbations&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> In addition&#44; Condreay et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> analysed in more detail the results of the METREX and METREO studies in order to identify genetic variants associated with the efficacy of Mepolizumab&#46; This post-hoc analysis failed to identify genetic effects on Mepolizumab-treatment response&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">More recently&#44; the results of another monoclonal antibody&#44; Benralizumab&#44; for the prevention of COPD exacerbations were published&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Benralizumab&#44; an IL-5 receptor alpha-directed monoclonal antibody was tested in two trials &#40;GALATHEA and TERRANOVA&#41; in patients with eosinophilic COPD &#40;&#62;220 per cubic millimeter&#41;&#46; Various doses of benralizumab were used vs placebo with primary end point the annual exacerbations&#46; The study showed that at 56 weeks&#44; none of the COPD exacerbation rate for any dose reached significance vs placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Basing the treatment on the number of eosinophils in the blood could be the wrong hypothesis&#44; since there is no strong evidence that they reflect the number and the function of the eosinophils in the lung tissue&#46; Tumor necrosis factor &#40;TNF&#41; inhibitors were shown to be effective in a small subgroup of severe asthma patients but were ineffective in COPD&#44; although they showed same effect among patients with COPD and rheumatoid arthritis&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">It is obvious that there are very few studies of monoclonal antibodies in COPD with controversial results for anti IL-5 or TNF-alpha and this may be because the pathogenesis of COPD at the cellular and molecular level is extremely complex&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> A large number of phenotypic pathways&#44; involving the immune system&#44; with even larger number of endotypes have been identified as playing a role in COPD&#46; Thus&#44; a single monoclonal antibody cannot be effective on all pathways and this may reflect that there is no dominant role for any single cytokine or chemokine in COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Better understanding of the pathogenesis of COPD at the cellular&#44; molecular&#44; genetic and immune levels may lead to more targeted use of monoclonal antibodies in restricted groups of patients with COPD with specific endotypes&#46; Although&#44; monoclonal antibodies could be the future of personalized treatment in COPD&#44; there is a long way to go before they became part of everyday practice in COPD&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">No conflict of interest to declare</p></span></span>"
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Editorial
Monoclonal antibodies for chronic obstructive pulmonary disease
Nikolaos Siafakas
Department of Thoracic Medicine, University of Crete, Medical School, Boutes, Heraklion, Crete, Greece
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Recently&#44; monoclonal antibodies have been used for the treatment of various severe diseases&#44; such as rheumatoid arthritis&#44; ankylosing spondylitis&#44; multiple sclerosis&#44; cancer infections among others&#46; They have immunomodulatory effects&#44; are prepared against specific cytokines&#44; inhibit specific enzymes or signaling molecules&#46; Today&#44; more than 60 monoclonal antibodies have been approved for clinical therapeutic use&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Monoclonal antibodies are generally well tolerated&#44; but those that suppress the immune system may reactivate latent infections&#44; such as tuberculosis or hepatitis B&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In pulmonary diseases&#44; monoclonal antibodies have been tested primarily in asthma with significant results&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The anti-IgE and the anti-interleukin-5 &#40;IL-5&#41; antibodies are now part of the regular treatment of severe asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The anti-IL-5 antibodies had been shown to be very effective in severe eosinophilic asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">These findings led to the hypothesis that these antibodies could be also effective in the sub-group of COPD patients with high eosinophilic counts in the blood&#46; Thereafter&#44; two monoclonal antibodies &#40;Mepolizumab&#44; Benralizumab&#41;&#44; both against IL-5 have been tested in eosinophilic COPD patients&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In 2017 Pavord et al&#46; performed two randomized&#44; placebo-controlled&#44; double-blind&#44; parallel-group trials of Mepolizumab &#40;METREY and METREO&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> One hundred mg in METREX and 100 or 300mg in METREO of Mepolizumab were given to an eosinophilic phenotype of COPD patients &#40;&#62;150 per cubic millimeter&#41;&#46; The primary end point in both trials was the annual rate of moderate or severe exacerbations&#46; It was concluded that Mepolizumab at a dose of 100<span class="elsevierStyleHsp" style=""></span>mg was associated with lower annual rate of exacerbations than placebo&#46; In addition it was shown that the greatest effect was found among patients with higher blood eosinophilic counts&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In 2019 Fernadez Romero et al&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> reviewed the literature of the clinical efficacy&#44; safety and side effects of Mepolizumab in the management of eosinophilic COPD patients and concluded that out of the three trials only one study showed significant effect on the annual rate of exacerbations&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> In addition&#44; Condreay et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> analysed in more detail the results of the METREX and METREO studies in order to identify genetic variants associated with the efficacy of Mepolizumab&#46; This post-hoc analysis failed to identify genetic effects on Mepolizumab-treatment response&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">More recently&#44; the results of another monoclonal antibody&#44; Benralizumab&#44; for the prevention of COPD exacerbations were published&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Benralizumab&#44; an IL-5 receptor alpha-directed monoclonal antibody was tested in two trials &#40;GALATHEA and TERRANOVA&#41; in patients with eosinophilic COPD &#40;&#62;220 per cubic millimeter&#41;&#46; Various doses of benralizumab were used vs placebo with primary end point the annual exacerbations&#46; The study showed that at 56 weeks&#44; none of the COPD exacerbation rate for any dose reached significance vs placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Basing the treatment on the number of eosinophils in the blood could be the wrong hypothesis&#44; since there is no strong evidence that they reflect the number and the function of the eosinophils in the lung tissue&#46; Tumor necrosis factor &#40;TNF&#41; inhibitors were shown to be effective in a small subgroup of severe asthma patients but were ineffective in COPD&#44; although they showed same effect among patients with COPD and rheumatoid arthritis&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">It is obvious that there are very few studies of monoclonal antibodies in COPD with controversial results for anti IL-5 or TNF-alpha and this may be because the pathogenesis of COPD at the cellular and molecular level is extremely complex&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> A large number of phenotypic pathways&#44; involving the immune system&#44; with even larger number of endotypes have been identified as playing a role in COPD&#46; Thus&#44; a single monoclonal antibody cannot be effective on all pathways and this may reflect that there is no dominant role for any single cytokine or chemokine in COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Better understanding of the pathogenesis of COPD at the cellular&#44; molecular&#44; genetic and immune levels may lead to more targeted use of monoclonal antibodies in restricted groups of patients with COPD with specific endotypes&#46; Although&#44; monoclonal antibodies could be the future of personalized treatment in COPD&#44; there is a long way to go before they became part of everyday practice in COPD&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">No conflict of interest to declare</p></span></span>"
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Article information
ISSN: 25310437
Original language: English
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2023 August 84 25 109
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2023 June 137 32 169
2023 May 143 33 176
2023 April 92 18 110
2023 March 144 29 173
2023 February 105 25 130
2023 January 78 26 104
2022 December 108 25 133
2022 November 83 40 123
2022 October 93 32 125
2022 September 100 43 143
2022 August 116 40 156
2022 July 111 57 168
2022 June 67 26 93
2022 May 82 31 113
2022 April 51 42 93
2022 March 77 47 124
2022 February 63 38 101
2022 January 108 38 146
2021 December 75 45 120
2021 November 82 40 122
2021 October 80 70 150
2021 September 116 52 168
2021 August 73 47 120
2021 July 80 26 106
2021 June 80 40 120
2021 May 112 54 166
2021 April 298 167 465
2021 March 186 84 270
2021 February 106 32 138
2021 January 80 42 122
2020 December 82 32 114
2020 November 82 29 111
2020 October 80 23 103
2020 September 105 40 145
2020 August 60 33 93
2020 July 86 36 122
2020 June 79 25 104
2020 May 106 38 144
2020 April 163 63 226
2020 March 116 61 177
2020 February 33 19 52
2020 January 28 21 49
2019 December 33 20 53
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Pulmonology

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