{"id":377921,"date":"2024-04-29T00:01:00","date_gmt":"2024-04-28T22:01:00","guid":{"rendered":"https:\/\/medizinonline.com\/?p=377921"},"modified":"2024-04-25T17:48:05","modified_gmt":"2024-04-25T15:48:05","slug":"which-patients-benefit-from-ics-as-an-add-on","status":"publish","type":"post","link":"https:\/\/medizinonline.com\/en\/which-patients-benefit-from-ics-as-an-add-on\/","title":{"rendered":"Which patients benefit from ICS as an add-on?"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\"><strong>The eosinophil count in the blood (EOS) is considered a suitable biomarker for deciding whether COPD patients are likely to derive additional clinical benefit from inhaled steroids (ICS) as an add-on. A secondary analysis by Dalin et al. supports the recommendation that from an EOS of 150 cells\/\u03bcL the addition of an ICS makes therapeutic sense. Above this threshold, a relevant reduction in the risk of exacerbation was demonstrated.<\/strong><\/p>\n\n<!--more-->\n\n<p class=\"wp-block-paragraph\">Current treatment recommendations, based on GOLD 2023, indicate that patients who have at least two further exacerbations or one exacerbation-related hospitalization despite treatment with LABA\/LAMA or LABA\/ICS benefit from the use of a triple combination of ICS\/LABA\/LAMA [1,2]. This appears to be particularly true in patients with a blood eosinophilia (EOS) of \u2265150 cells\/ \u03bcL [2\u20134]. Various studies have contributed to the fact that the value of inhaled steroids (ICS) in COPD has increased over time.<br\/>has changed over time. Positive effects of ICS in COPD with regard to exacerbations and other parameters were first reported in the<br\/>This was demonstrated in 2000 in the ISOLDE study [5]. Surprisingly, the TORCH study conducted in 2007 was unable to demonstrate a reduction in overall mortality, but did show significant benefits in all other endpoints [6]. In 2016, a long-acting beta-2 mimetic plus a long-acting anticholinergic agent (LABA\/LAMA) proved to be superior to a LABA\/ICS combination in the prevention of exacerbations in the FLAME study [7]. This questioned the role of ICS in patients with COPD. However, several recent studies show that certain COPD subgroups benefit from ICS as an add-on [10]. An additional benefit of the triple combination ICS\/LABA\/LAMA was recently demonstrated in the IMPACT and ETHOS studies [8,9].  <\/p>\n\n<h3 id=\"why-blood-eosinophilia-is-suitable-as-a-biomarker\" class=\"wp-block-heading\">Why blood eosinophilia is suitable as a biomarker  <\/h3>\n\n<p class=\"wp-block-paragraph\">ICS have anti-inflammatory effects and the eosinophil count in sputum correlates with the degree of inflammation in the lungs [10\u201312]. Therefore, the eosinophil count in the blood acts as a relevant biomarker for deciding whether ICS treatment is appropriate in patients with COPD. Previous studies have shown that COPD patients with blood eosinophils above 2% respond better to treatment with systemic steroids compared to those with lower levels [13,14]. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), blood eosinophils should be measured in absolute numbers (cells\/\u03bcL), which is how this has been done in recent studies [15,16]. The cut-off value regarding EOS for an ICS indication in COPD is the subject of controversial debate. From a meta-analysis published in 2022 by Dalin et al. shows that COPD patients with an EOS of \u2265150 cells\/\u03bcL have an additional benefit from the use of an ICS. The PROSPERO study, funded by the Danish Health Authority, included 11 RCTs with a total of 29,654 patients, with ICS used in double and triple combinations [10]. From an EOS of 150 cells\/\u03bcl, there was a clear correlation between continued ICS treatment in terms of the number of exacerbations, lung function and quality of life. The RCTs with an ICS\/LABA\/LAMA study arm are shown in <strong>Table 1<\/strong> [10].  <\/p>\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full is-resized\"><a href=\"https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33.png\"><img fetchpriority=\"high\" decoding=\"async\" width=\"2177\" height=\"1366\" src=\"https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33.png\" alt=\"\" class=\"wp-image-377868\" style=\"width:500px\" srcset=\"https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33.png 2177w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-800x502.png 800w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-1160x728.png 1160w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-2048x1285.png 2048w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-120x75.png 120w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-90x56.png 90w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-320x201.png 320w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-560x351.png 560w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-1920x1205.png 1920w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-240x151.png 240w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-180x113.png 180w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-640x402.png 640w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-1120x703.png 1120w, https:\/\/medizinonline.com\/wp-content\/uploads\/2024\/04\/tab1_HP4_s33-1600x1004.png 1600w\" sizes=\"(max-width: 2177px) 100vw, 2177px\" \/><\/a><\/figure>\n<\/div>\n<h3 id=\"the-higher-the-blood-eosinophilia-the-greater-the-additional-benefit\" class=\"wp-block-heading\">The higher the blood eosinophilia, the greater the additional benefit  <\/h3>\n\n<p class=\"wp-block-paragraph\">In the meta-analysis by Dalin et al. the relative reduction in the risk of a moderate to severe exacerbation with an EOS &lt;150 cells\/\u03bcl was 12% (ratio: 0.88; 95% CI: 0.83-0.94). [10]. With an EOS in the range of 150-300 cells\/\u03bcL, a relative reduction of 20% was observed (ratio: 0.80; 95% CI: 0.69-0.94). And in patients with an EOS &gt;300 cells\/\u03bcL, there was a clinically relevant reduction of 43% (ratio: 0.57; 95% CI: 0.49-0.66). The differences in risk reduction between the three EOS subgroups proved to be significant (p&lt;0.00001). In patients with an EOS in the range of 150-300 cells\/\u03bcL and &gt;300 cells\/\u03bcL, continued treatment with ICS improved lung function by 0.05 L (mean <sub>FEV1<\/sub> difference; 95% CI: 0.03-0.07 L) and 0.06 L (mean <sub>FEV1<\/sub> difference; 95% CI: 0.04-0.09 L), respectively. A test for differences in the subgroups showed that continued ICS treatment had a different effect on lung function in the subgroups (p=0.04), with patients with an EOS \u2265150 cells\/\u03bcL showing a greater improvement than patients with lower EOS values. In patients with EOS &lt;150 cells\/\u03bcL, continued ICS treatment probably had no effect on lung function (mean <sub>FEV1<\/sub> difference: 0.02 L; 95% CI: 0.00-0.05 L). Regardless of the EOS subgroups, continued treatment with ICS increased the risk of pneumonia (risk ratio: 1.39; 95% CI: 1.19-1.63).  <\/p>\n\n<p class=\"wp-block-paragraph\">Literature:  <\/p>\n\n<ol class=\"wp-block-list\">\n<li>Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease report; 2023, <a href=\"https:\/\/goldcopd.org\/2023-gold-report-2\" target=\"_blank\" rel=\"noopener\">https:\/\/goldcopd.org\/2023-gold-report-2,<\/a>(last accessed 19.03.2024)  <\/li>\n\n\n\n<li>COPD, Guideline short version: <a href=\"http:\/\/www.medix-guidelines.ch\/lungenkrankheiten\/copd\" target=\"_blank\" rel=\"noopener\">www.medix-guidelines.ch\/lungenkrankheiten\/copd,<\/a> last update: 08\/2023, (last accessed 19.03.2024)  <\/li>\n\n\n\n<li>Wegewitz U, et al: Resuming the discussion of AMSTAR: what can (should) be made better? BMC Med Res Methodol 2016; 16.  <\/li>\n\n\n\n<li>Scherer RW, Saldanha IJ: How should systematic reviewers handle conference abstracts? A view from the trenches. Syst Rev 2019; 8: 264.  <\/li>\n\n\n\n<li>Burge PS, et al: Randomized, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ. 2000; 320: 1297-1303.  <\/li>\n\n\n\n<li>Calverley PMA, et al: TORCH investigators, Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. NEJM 2007; 356: 775-789.  <\/li>\n\n\n\n<li>Wedzicha JA, et al: FLAME investigators, indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. NEJM 2016; 374: 2222-2234.  <\/li>\n\n\n\n<li>Pascoe S, et al: Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial. Lancet Respir Med 2019; 7: 745-756.  <\/li>\n\n\n\n<li>Rabe KF, et al: ETHOS investigators, triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. NEJM 2020; 383: 35-48.  <\/li>\n\n\n\n<li>Dalin DA, et al: A systematic review of blood eosinophils and continued treatment with inhaled corticosteroids in patients with COPD. Respir Med 2022 Jul; 198: 106880.  <\/li>\n\n\n\n<li>  Brightling CE, et al: Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease. Thorax 2005; 60: 193-198.  <\/li>\n\n\n\n<li>Tashkin DP, Wechsler ME: Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease. Int J Chronic Obstr Pulm Dis 2018; 13: 335-349.  <\/li>\n\n\n\n<li>Bafadhel M, et al: Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012; 186: 48-55.  <\/li>\n\n\n\n<li>Bafadhel M, et al: Blood eosinophil guided prednisolone therapy for exacerbations of COPD: a further analysis. Eur Respir J 2014; 44: 789-791.  <\/li>\n\n\n\n<li>Global Initiative for Chronic Obstructive Lung Disease GOLD Global Strategy for Prevention, Diagnosis and Management of COPD (2019 Report).<\/li>\n\n\n\n<li>Global Initiative for Chronic Obstructive Lung Disease GOLD Global Strategy for Prevention, Diagnosis and Management of COPD, 2021 Report.  <\/li>\n\n\n\n<li>Bafadhel M, et al: Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomized trials. Lancet Respir. Med. 2018; 6: 117-126.  <\/li>\n\n\n\n<li>Goyal P, et al: Comparison of effect of indacaterol with salmeterol\/fluticasone fixed dose combination on COPD exacerbations based on baseline blood eosinophil counts: post-hoc analysis from the instead study. Respirology 2015; 20 (n.d.): 43.  <\/li>\n\n\n\n<li>Ferguson GT, et al: Triple therapy with budesonide\/glycopyrrolate\/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomized controlled trial. Lancet Respir Med 2018; 6: 747-758.  <\/li>\n\n\n\n<li>Pascoe S, et al: Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. Lancet Respir Med 2015; 3: 435-442. <\/li>\n\n\n\n<li>Hanania NA, et al: Efficacy and safety of two doses of budesonide\/formoterol fumarate metered dose inhaler in COPD. ERJ Open Res 2020; 6.  <\/li>\n\n\n\n<li>Chapman KR, et al: Long-Term triple therapy de-escalation to indacaterol\/glycopyrronium in patients with chronic obstructive pulmonary disease (SUNSET): a randomized, double-blind, triple-dummy clinical trial. Am J Respir Crit Care Med 2018; 198: 329-339.  <\/li>\n\n\n\n<li>Papi A, et al: Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomized controlled trial. Lancet Lond Engl 2018; 391: 1076-1108.  <\/li>\n\n\n\n<li>Watz H, et al: Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: a post-hoc analysis of the WISDOM trial. Lancet Respir Med 2016; 4: 390-398.  <\/li>\n\n\n\n<li>Siddiqui SH, et al: Blood eosinophils: a biomarker of response to extrafine beclomethasone\/formoterol in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2015; 192: 523-552.  <\/li>\n<\/ol>\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n<p class=\"has-small-font-size wp-block-paragraph\"><em>FAMILY PHYSICIAN PRACTICE 2024; 19(4): 33-34<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The eosinophil count in the blood (EOS) is considered a suitable biomarker for deciding whether COPD patients are likely to derive additional clinical benefit from inhaled steroids (ICS) as an&hellip;<\/p>\n","protected":false},"author":7,"featured_media":270985,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"pmpro_default_level":"","cat_1_feature_home_top":false,"cat_2_editor_pick":false,"csco_eyebrow_text":"COPD ","footnotes":""},"category":[11508,11297,11455,11548,11503],"tags":[23472,12085,75241,75238,18866,13728],"powerkit_post_featured":[],"class_list":["post-377921","post","type-post","status-publish","format-standard","has-post-thumbnail","category-education","category-general-internal-medicine","category-pneumology","category-rx-en","category-studies","tag-add-on-en","tag-copd-en","tag-dalin-et-al-en","tag-eosinophil-count-in-the-blood","tag-exacerbations","tag-ics-en","pmpro-has-access"],"acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-06-17 06:00:21","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"wpml_current_locale":"en_US","wpml_translations":{"fr_FR":{"locale":"fr_FR","id":377934,"slug":"quels-sont-les-patients-qui-beneficient-des-ics-en-tant-quadd-on","post_title":"Quels sont les patients qui b\u00e9n\u00e9ficient des ICS en tant qu'add-on ?","href":"https:\/\/medizinonline.com\/fr\/quels-sont-les-patients-qui-beneficient-des-ics-en-tant-quadd-on\/"},"it_IT":{"locale":"it_IT","id":377949,"slug":"quali-pazienti-beneficiano-dellics-come-add-on","post_title":"Quali pazienti beneficiano dell'ICS come add-on?","href":"https:\/\/medizinonline.com\/it\/quali-pazienti-beneficiano-dellics-come-add-on\/"},"pt_PT":{"locale":"pt_PT","id":377960,"slug":"quais-sao-os-doentes-que-beneficiam-de-ics-como-tratamento-complementar","post_title":"Quais s\u00e3o os doentes que beneficiam de ICS como tratamento complementar?","href":"https:\/\/medizinonline.com\/pt-pt\/quais-sao-os-doentes-que-beneficiam-de-ics-como-tratamento-complementar\/"},"es_ES":{"locale":"es_ES","id":377973,"slug":"que-pacientes-se-benefician-de-los-csi-como-complemento","post_title":"\u00bfQu\u00e9 pacientes se benefician de los CSI como complemento?","href":"https:\/\/medizinonline.com\/es\/que-pacientes-se-benefician-de-los-csi-como-complemento\/"}},"_links":{"self":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/377921","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/comments?post=377921"}],"version-history":[{"count":1,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/377921\/revisions"}],"predecessor-version":[{"id":377929,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/377921\/revisions\/377929"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media\/270985"}],"wp:attachment":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media?parent=377921"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/category?post=377921"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/tags?post=377921"},{"taxonomy":"powerkit_post_featured","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/powerkit_post_featured?post=377921"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}