Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory condition affecting the upper airways, with chronic symptoms such as nasal congestion, partial (hyposmia) or total (anosmia) loss of smell, anterior/posterior rhinorrhea, and mild facial pain.1 As many as 66% of patients with...
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| Veröffentlicht in: | The journal of allergy and clinical immunology in practice (Cambridge, MA) MA), 2019-09, Vol.7 (7), p.2447-2449.e2 |
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| creator | Bachert, Claus Hellings, Peter W. Mullol, Joaquim Naclerio, Robert M. Chao, Jingdong Amin, Nikhil Grabher, Annette Swanson, Brian N. Hamilton, Jennifer D. Guillonneau, Sophie Taniou, Christine Zhang, Donghui Pirozzi, Gianluca Graham, Neil M.H. Staudinger, Heribert Mannent, Leda P. Khan, Asif |
| description | Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory condition affecting the upper airways, with chronic symptoms such as nasal congestion, partial (hyposmia) or total (anosmia) loss of smell, anterior/posterior rhinorrhea, and mild facial pain.1 As many as 66% of patients with CRSwNP have comorbid asthma and suffer from more severe nasal obstruction, higher levels of lower airway inflammation, and worse asthma control than those without CRS.2,3 Thus, patients with CRSwNP and comorbid asthma have a high disease burden, seriously impacting health-related quality of life (HRQoL).2,3 Markers of type 2-mediated inflammation and antibody production (eg, IL-5, IgE) are associated with both CRSwNP and asthma pathogenesis.2 Dupilumab, a fully human VelocImmune-derived4,5 monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13, thus inhibiting signaling of both IL-4 and IL-13, key drivers of type 2 diseases such as atopic dermatitis, asthma, and allergic rhinitis.6 In a 16-week phase 2a study in adults with CRSwNP refractory to intranasal corticosteroids (INCS), adding dupilumab to mometasone furoate nasal spray (MFNS) reduced nasal polyp burden versus MFNS alone and significantly improved nasal congestion and airflow, sense of smell, HRQoL, and other nasal symptoms.7 We present a subgroup analysis of patients with CRSwNP and comorbid asthma from this study, examining the effect of dupilumab on patient-reported outcomes (PROs) for CRSwNP and asthma, and inflammatory biomarkers. EQ-5D VAS provides a simple measure of the patient's self-rated health on a vertical virtual analog scale, with scores 0 to 100 mm (worst-best imaginable health state).8 SF-36 comprises 8 domains assessing physical functioning, social functioning, role limitations due to physical and emotional problems, mental health, energy/vitality, bodily pain, and general health perception. Two summary scores, the physical (PCS) and mental health component summary, are calculated by the aggregation of the 8 SF-36 subscales, to evaluate the physical and mental health, respectively (higher scores indicating better HRQoL).9 The effects of dupilumab on the individual ACQ-5 scores (woken at night by asthma, awake in morning with asthma symptoms, limited in activities, shortness of breath, wheezing time), as well as inflammatory biomarkers (eosinophils, eosinophil cationic protein, thymus and activation-regulated chemokine, IgE, and periostin), were also assessed. [.. |
| doi_str_mv | 10.1016/j.jaip.2019.03.023 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_480872</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S2213219819303046</els_id><sourcerecordid>2284480777</sourcerecordid><originalsourceid>FETCH-LOGICAL-c516t-d0f9f0e411726d06863a1ac8d7316ec3564f425f705ce967d64b6173220164e33</originalsourceid><addsrcrecordid>eNp9kk2LFDEQhoMo7jLuH_AgAS9eus1Hd5IGL7LrFyx40XNIJ9VMxu5Om6R3WX-9aWZmBUFzSVH1vEXxViH0kpKaEireHuqD8UvNCO1qwmvC-BN0yRjlFSu5p-eYduoCXaV0IOUpKklDnqMLTjqmRKsu0a-bdfHjOpke-2mJ4Q4SXkz2MOcqwhJiBofDmm2YSsXP52LC9z7vsd3HMHuL497PIfl5TT77U202yYx4CePDkrCZHS49Quy9wybl_WReoGeDGRNcnf4d-v7xw7frz9Xt109frt_fVralIleODN1AoKFUMuGIUIIbaqxyklMBlreiGRrWDpK0FjohnWh6QSXfbBANcL5D1bFvuodl7fUS_WTigw7G61PqR4lAN4ooyQrf_ZMvDrk_orOQNlSqdjN8h94ctQX8uULKevLJwjiaGcKa9DaUpK1iqqCv_0IPYY1zcaJQqinDSCkLxY6UjSGlCMPjOJTo7RD0QW-HoLdD0ITrcghF9OrUeu0ncI-S89oL8O4IQPH9zkPUyZatWnA-gs3aBf-__r8B5YjGeQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2284480777</pqid></control><display><type>article</type><title>Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma</title><source>SWEPUB Freely available online</source><source>Alma/SFX Local Collection</source><creator>Bachert, Claus ; Hellings, Peter W. ; Mullol, Joaquim ; Naclerio, Robert M. ; Chao, Jingdong ; Amin, Nikhil ; Grabher, Annette ; Swanson, Brian N. ; Hamilton, Jennifer D. ; Guillonneau, Sophie ; Taniou, Christine ; Zhang, Donghui ; Pirozzi, Gianluca ; Graham, Neil M.H. ; Staudinger, Heribert ; Mannent, Leda P. ; Khan, Asif</creator><creatorcontrib>Bachert, Claus ; Hellings, Peter W. ; Mullol, Joaquim ; Naclerio, Robert M. ; Chao, Jingdong ; Amin, Nikhil ; Grabher, Annette ; Swanson, Brian N. ; Hamilton, Jennifer D. ; Guillonneau, Sophie ; Taniou, Christine ; Zhang, Donghui ; Pirozzi, Gianluca ; Graham, Neil M.H. ; Staudinger, Heribert ; Mannent, Leda P. ; Khan, Asif</creatorcontrib><description>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory condition affecting the upper airways, with chronic symptoms such as nasal congestion, partial (hyposmia) or total (anosmia) loss of smell, anterior/posterior rhinorrhea, and mild facial pain.1 As many as 66% of patients with CRSwNP have comorbid asthma and suffer from more severe nasal obstruction, higher levels of lower airway inflammation, and worse asthma control than those without CRS.2,3 Thus, patients with CRSwNP and comorbid asthma have a high disease burden, seriously impacting health-related quality of life (HRQoL).2,3 Markers of type 2-mediated inflammation and antibody production (eg, IL-5, IgE) are associated with both CRSwNP and asthma pathogenesis.2 Dupilumab, a fully human VelocImmune-derived4,5 monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13, thus inhibiting signaling of both IL-4 and IL-13, key drivers of type 2 diseases such as atopic dermatitis, asthma, and allergic rhinitis.6 In a 16-week phase 2a study in adults with CRSwNP refractory to intranasal corticosteroids (INCS), adding dupilumab to mometasone furoate nasal spray (MFNS) reduced nasal polyp burden versus MFNS alone and significantly improved nasal congestion and airflow, sense of smell, HRQoL, and other nasal symptoms.7 We present a subgroup analysis of patients with CRSwNP and comorbid asthma from this study, examining the effect of dupilumab on patient-reported outcomes (PROs) for CRSwNP and asthma, and inflammatory biomarkers. EQ-5D VAS provides a simple measure of the patient's self-rated health on a vertical virtual analog scale, with scores 0 to 100 mm (worst-best imaginable health state).8 SF-36 comprises 8 domains assessing physical functioning, social functioning, role limitations due to physical and emotional problems, mental health, energy/vitality, bodily pain, and general health perception. Two summary scores, the physical (PCS) and mental health component summary, are calculated by the aggregation of the 8 SF-36 subscales, to evaluate the physical and mental health, respectively (higher scores indicating better HRQoL).9 The effects of dupilumab on the individual ACQ-5 scores (woken at night by asthma, awake in morning with asthma symptoms, limited in activities, shortness of breath, wheezing time), as well as inflammatory biomarkers (eosinophils, eosinophil cationic protein, thymus and activation-regulated chemokine, IgE, and periostin), were also assessed. [...]treatment with dupilumab was associated with an improvement of both clinical and patient-reported NP-specific outcomes, and asthma-specific outcomes in patients with CRSwNP and comorbid asthma.Acknowledgments Editorial assistance was provided by Bilge Yoruk, PhD, and Ravi Subramanian, PhD, of Excerpta Medica funded by Sanofi Genzyme and Regeneron Pharmaceuticals.Online Repository ACQ-5† Measure Mean score (SD) at baseline LS mean change (SE) from baseline to week 16 LS mean difference for dupilumab vs placebo (95% CI) Placebo/MFNS (n = 19) Dupilumab/MFNS (n = 16) Placebo/MFNS (n = 12) Dupilumab/MFNS (n = 15) Total overall‡ Total 1.63 (0.87) 1.55 (1.11) −0.10 (0.20) −1.19 (0.19) −1.09 (−1.54, −0.63)∗∗∗ Item 1§ Woken at night by asthma 1.00 (1.10) 0.88 (1.45) 0.08 (0.24) –0.91 (0.23) –0.99 (–1.55, –0.42)∗∗ Item 2§ Awake in morning with asthma symptoms 2.00 (1.37) 1.69 (1.25) 0.01 (0.22) –1.46 (0.20) –1.46 (–1.94, –0.99)∗∗∗ Item 3§ Limited in activities 1.38 (1.20) 1.25 (1.13) –0.11 (0.23) –0.93 (0.21) –0.83 (–1.34, –0.32)∗∗ Item 4§ Shortness of breath 2.19 (1.33) 1.94 (1.24) –0.29 (0.29) –1.33 (0.27) –1.04 (–1.77, –0.31)∗∗ Item 5§ Wheezing time 1.56 (0.63) 2.00 (1.90) –0.54 (0.36) –1.50 (0.34) –0.96 (–1.81, –0.12)∗ Table I ACQ-5 scores at baseline and change from baseline at week 16 in patients with CRSwNP and comorbid asthma Placebo/MFNS (n = 19) Dupilumab/MFNS (n = 16) Patient characteristic Age, mean (SD), y 47.7 (9.9) 51.4 (7.6) Male, n (%) 7 (36.8) 7 (43.8) Duration of CRSwNP, mean (SD), y 11.32 (8.93) 8.95 (6.33) Duration of asthma, mean (SD), y 20.15 (17.40) 15.46 (12.13) Patients with aspirin-sensitive asthma, n (%) 8 (42.1) 5 (31.3) Baseline measures of CRSwNP Nasal polyps endoscopic score, range 0-8∗, mean (SD) 5.53 (1.02) 5.94 (0.85) CT Lund-Mackay total score, range 0-24∗, mean (SD) 19.95 (5.65) 19.07 (4.23) CRSwNP disease severity VAS (0-10 cm)∗, mean (SD) 6.66 (2.36) 6.23 (2.73) Daily congestion/obstruction score (0-3)† 1.67 (0.74) 1.43 (0.73) Daily AM loss of smell score† (0-3)† 2.93 (0.24) 2.47 (0.96) SNOT-22 total score (0-110), mean (SD)∗ 43.63 (20.66) 40.63 (16.26) Baseline measures of asthma ACQ-5 total score, mean (SD) 1.63 (0.87) 1.55 (1.11) Baseline FEV1, mean (SD), % predicted 79.76 (14.55) 82.19 (17.71) Baseline levels of biomarkers Serum blood eosinophil count, mean (SD), 109/L 0.55 (0.83) 0.51 (0.25) Serum ECP, mean (SD), ng/mL 37.26 (48.33) 35.38 (26.27) Nasal secretion ECP, mean (SD), ng/mL 16.47 (11.49) 41.80 (43.44) Serum total IgE, mean (SD), IU/mL 233.06 (300.44) 167.13 (153.77) Nasal secretion total IgE, mean (SD), IU/mL 7.53 (5.64) 20.93 (41.78) Serum TARC, mean (SD), pg/mL 506.20 (422.59) 506.77 (340.29) Serum periostin, mean (SD), ng/mL 72.86 (28.52) 80.42 (24.44) Nasal secretion periostin, mean (SD), ng/mL 6.92 (5.44) 7.27 (5.78) Table E1 Baseline demographics and disease characteristics of patients with CRSwNP with comorbid asthma Biomarker Placebo/MFNS group (n = 19) Dupilumab/MFNS group (n = 16) LS mean difference for dupilumab vs placebo at week 16 (95% CI)∗ P value Baseline mean (SD) Week 16 mean (SD) LS mean change from baseline (SE) Baseline mean (SD) Week 16 mean (SD) LS mean change from baseline (SE) Serum blood eosinophil count, 109/L 0.55 (0.83) 0.37 (0.19) –0.15 (0.17) 0.51 (0.25) 0.53 (0.37) –0.06 (0.16) 0.09 (–0.34, 0.51) .682 Serum ECP, ng/mL 37.26 (48.33) 15.57 (11.92) –14.58 (9.83) 35.38 (26.27) 41.60 (47.60) 6.66 (9.77) 21.25 (–3.70, 46.20) .094 Nasal secretion ECP, ng/mL 16.47 (11.49) 29.08 (38.72) 26.47 (11.31) 41.80 (43.44) 39.07 (38.19) 16.92 (9.98) –9.55 (–35.89, 16.80) .472 Serum total IgE, IU/mL 233.06 (300.44) 128.87 (143.70) –38.09 (12.22) 167.13 (153.77) 102.07 (119.46) –86.59 (12.38) –48.49 (–78.66, –18.33) .002 Nasal secretion total IgE, IU/mL 7.53 (5.64) 13.77 (21.46) 6.86 (5.03) 20.93 (41.78) 5.53 (4.05) –5.31 (4.31) –12.17 (–23.76, –0.57) .04 Serum TARC, pg/mL 506.20 (422.59) 384.19 (235.65) –125.80 (44.78) 506.77 (340.29) 288.94 (154.06) –204.62 (48.99) –78.82 (–183.10, 25.45) .135 Serum periostin, ng/mL 72.86 (28.52) 53.05 (18.76) –17.09 (7.52) 80.42 (24.44) 57.83 (22.27) –13.83 (6.53) 3.26 (–13.05, 19.57) .692 Nasal secretion periostin, ng/mL 6.92 (5.44) 8.37 (6.91) 0.64 (2.53) 7.27 (5.78) 4.26 (5.71) –2.96 (2.16) –3.60 (–7.60, 0.40) .076 Table E2 Inflammatory biomarker levels at baseline and change from baseline at week 16 in patients with CRSwNP and comorbid asthma</description><identifier>ISSN: 2213-2198</identifier><identifier>ISSN: 2213-2201</identifier><identifier>EISSN: 2213-2201</identifier><identifier>DOI: 10.1016/j.jaip.2019.03.023</identifier><identifier>PMID: 30928658</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Allergic rhinitis ; Anosmia ; Aspirin ; Asthma ; Atopic dermatitis ; Biomarkers ; CCL17 protein ; Cell activation ; Chemokines ; Clinical outcomes ; Comorbidity ; Corticosteroids ; Demography ; Endoscopy ; Immunoglobulin E ; Immunotherapy ; Inflammation ; Interleukin 13 ; Interleukin 4 ; Interleukin 5 ; Leukocytes (eosinophilic) ; Medicin och hälsovetenskap ; Mental disorders ; Mental health ; Monoclonal antibodies ; Nose ; Olfaction ; Pain ; Pain perception ; Patients ; Polyps ; Quality of life ; Questionnaires ; Respiratory tract ; Respiratory tract diseases ; Rhinitis ; Sinusitis ; Thymus</subject><ispartof>The journal of allergy and clinical immunology in practice (Cambridge, MA), 2019-09, Vol.7 (7), p.2447-2449.e2</ispartof><rights>2019 The Authors</rights><rights>2019. The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c516t-d0f9f0e411726d06863a1ac8d7316ec3564f425f705ce967d64b6173220164e33</citedby><cites>FETCH-LOGICAL-c516t-d0f9f0e411726d06863a1ac8d7316ec3564f425f705ce967d64b6173220164e33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,553,781,785,886,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30928658$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:141785221$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Bachert, Claus</creatorcontrib><creatorcontrib>Hellings, Peter W.</creatorcontrib><creatorcontrib>Mullol, Joaquim</creatorcontrib><creatorcontrib>Naclerio, Robert M.</creatorcontrib><creatorcontrib>Chao, Jingdong</creatorcontrib><creatorcontrib>Amin, Nikhil</creatorcontrib><creatorcontrib>Grabher, Annette</creatorcontrib><creatorcontrib>Swanson, Brian N.</creatorcontrib><creatorcontrib>Hamilton, Jennifer D.</creatorcontrib><creatorcontrib>Guillonneau, Sophie</creatorcontrib><creatorcontrib>Taniou, Christine</creatorcontrib><creatorcontrib>Zhang, Donghui</creatorcontrib><creatorcontrib>Pirozzi, Gianluca</creatorcontrib><creatorcontrib>Graham, Neil M.H.</creatorcontrib><creatorcontrib>Staudinger, Heribert</creatorcontrib><creatorcontrib>Mannent, Leda P.</creatorcontrib><creatorcontrib>Khan, Asif</creatorcontrib><title>Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma</title><title>The journal of allergy and clinical immunology in practice (Cambridge, MA)</title><addtitle>J Allergy Clin Immunol Pract</addtitle><description>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory condition affecting the upper airways, with chronic symptoms such as nasal congestion, partial (hyposmia) or total (anosmia) loss of smell, anterior/posterior rhinorrhea, and mild facial pain.1 As many as 66% of patients with CRSwNP have comorbid asthma and suffer from more severe nasal obstruction, higher levels of lower airway inflammation, and worse asthma control than those without CRS.2,3 Thus, patients with CRSwNP and comorbid asthma have a high disease burden, seriously impacting health-related quality of life (HRQoL).2,3 Markers of type 2-mediated inflammation and antibody production (eg, IL-5, IgE) are associated with both CRSwNP and asthma pathogenesis.2 Dupilumab, a fully human VelocImmune-derived4,5 monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13, thus inhibiting signaling of both IL-4 and IL-13, key drivers of type 2 diseases such as atopic dermatitis, asthma, and allergic rhinitis.6 In a 16-week phase 2a study in adults with CRSwNP refractory to intranasal corticosteroids (INCS), adding dupilumab to mometasone furoate nasal spray (MFNS) reduced nasal polyp burden versus MFNS alone and significantly improved nasal congestion and airflow, sense of smell, HRQoL, and other nasal symptoms.7 We present a subgroup analysis of patients with CRSwNP and comorbid asthma from this study, examining the effect of dupilumab on patient-reported outcomes (PROs) for CRSwNP and asthma, and inflammatory biomarkers. EQ-5D VAS provides a simple measure of the patient's self-rated health on a vertical virtual analog scale, with scores 0 to 100 mm (worst-best imaginable health state).8 SF-36 comprises 8 domains assessing physical functioning, social functioning, role limitations due to physical and emotional problems, mental health, energy/vitality, bodily pain, and general health perception. Two summary scores, the physical (PCS) and mental health component summary, are calculated by the aggregation of the 8 SF-36 subscales, to evaluate the physical and mental health, respectively (higher scores indicating better HRQoL).9 The effects of dupilumab on the individual ACQ-5 scores (woken at night by asthma, awake in morning with asthma symptoms, limited in activities, shortness of breath, wheezing time), as well as inflammatory biomarkers (eosinophils, eosinophil cationic protein, thymus and activation-regulated chemokine, IgE, and periostin), were also assessed. [...]treatment with dupilumab was associated with an improvement of both clinical and patient-reported NP-specific outcomes, and asthma-specific outcomes in patients with CRSwNP and comorbid asthma.Acknowledgments Editorial assistance was provided by Bilge Yoruk, PhD, and Ravi Subramanian, PhD, of Excerpta Medica funded by Sanofi Genzyme and Regeneron Pharmaceuticals.Online Repository ACQ-5† Measure Mean score (SD) at baseline LS mean change (SE) from baseline to week 16 LS mean difference for dupilumab vs placebo (95% CI) Placebo/MFNS (n = 19) Dupilumab/MFNS (n = 16) Placebo/MFNS (n = 12) Dupilumab/MFNS (n = 15) Total overall‡ Total 1.63 (0.87) 1.55 (1.11) −0.10 (0.20) −1.19 (0.19) −1.09 (−1.54, −0.63)∗∗∗ Item 1§ Woken at night by asthma 1.00 (1.10) 0.88 (1.45) 0.08 (0.24) –0.91 (0.23) –0.99 (–1.55, –0.42)∗∗ Item 2§ Awake in morning with asthma symptoms 2.00 (1.37) 1.69 (1.25) 0.01 (0.22) –1.46 (0.20) –1.46 (–1.94, –0.99)∗∗∗ Item 3§ Limited in activities 1.38 (1.20) 1.25 (1.13) –0.11 (0.23) –0.93 (0.21) –0.83 (–1.34, –0.32)∗∗ Item 4§ Shortness of breath 2.19 (1.33) 1.94 (1.24) –0.29 (0.29) –1.33 (0.27) –1.04 (–1.77, –0.31)∗∗ Item 5§ Wheezing time 1.56 (0.63) 2.00 (1.90) –0.54 (0.36) –1.50 (0.34) –0.96 (–1.81, –0.12)∗ Table I ACQ-5 scores at baseline and change from baseline at week 16 in patients with CRSwNP and comorbid asthma Placebo/MFNS (n = 19) Dupilumab/MFNS (n = 16) Patient characteristic Age, mean (SD), y 47.7 (9.9) 51.4 (7.6) Male, n (%) 7 (36.8) 7 (43.8) Duration of CRSwNP, mean (SD), y 11.32 (8.93) 8.95 (6.33) Duration of asthma, mean (SD), y 20.15 (17.40) 15.46 (12.13) Patients with aspirin-sensitive asthma, n (%) 8 (42.1) 5 (31.3) Baseline measures of CRSwNP Nasal polyps endoscopic score, range 0-8∗, mean (SD) 5.53 (1.02) 5.94 (0.85) CT Lund-Mackay total score, range 0-24∗, mean (SD) 19.95 (5.65) 19.07 (4.23) CRSwNP disease severity VAS (0-10 cm)∗, mean (SD) 6.66 (2.36) 6.23 (2.73) Daily congestion/obstruction score (0-3)† 1.67 (0.74) 1.43 (0.73) Daily AM loss of smell score† (0-3)† 2.93 (0.24) 2.47 (0.96) SNOT-22 total score (0-110), mean (SD)∗ 43.63 (20.66) 40.63 (16.26) Baseline measures of asthma ACQ-5 total score, mean (SD) 1.63 (0.87) 1.55 (1.11) Baseline FEV1, mean (SD), % predicted 79.76 (14.55) 82.19 (17.71) Baseline levels of biomarkers Serum blood eosinophil count, mean (SD), 109/L 0.55 (0.83) 0.51 (0.25) Serum ECP, mean (SD), ng/mL 37.26 (48.33) 35.38 (26.27) Nasal secretion ECP, mean (SD), ng/mL 16.47 (11.49) 41.80 (43.44) Serum total IgE, mean (SD), IU/mL 233.06 (300.44) 167.13 (153.77) Nasal secretion total IgE, mean (SD), IU/mL 7.53 (5.64) 20.93 (41.78) Serum TARC, mean (SD), pg/mL 506.20 (422.59) 506.77 (340.29) Serum periostin, mean (SD), ng/mL 72.86 (28.52) 80.42 (24.44) Nasal secretion periostin, mean (SD), ng/mL 6.92 (5.44) 7.27 (5.78) Table E1 Baseline demographics and disease characteristics of patients with CRSwNP with comorbid asthma Biomarker Placebo/MFNS group (n = 19) Dupilumab/MFNS group (n = 16) LS mean difference for dupilumab vs placebo at week 16 (95% CI)∗ P value Baseline mean (SD) Week 16 mean (SD) LS mean change from baseline (SE) Baseline mean (SD) Week 16 mean (SD) LS mean change from baseline (SE) Serum blood eosinophil count, 109/L 0.55 (0.83) 0.37 (0.19) –0.15 (0.17) 0.51 (0.25) 0.53 (0.37) –0.06 (0.16) 0.09 (–0.34, 0.51) .682 Serum ECP, ng/mL 37.26 (48.33) 15.57 (11.92) –14.58 (9.83) 35.38 (26.27) 41.60 (47.60) 6.66 (9.77) 21.25 (–3.70, 46.20) .094 Nasal secretion ECP, ng/mL 16.47 (11.49) 29.08 (38.72) 26.47 (11.31) 41.80 (43.44) 39.07 (38.19) 16.92 (9.98) –9.55 (–35.89, 16.80) .472 Serum total IgE, IU/mL 233.06 (300.44) 128.87 (143.70) –38.09 (12.22) 167.13 (153.77) 102.07 (119.46) –86.59 (12.38) –48.49 (–78.66, –18.33) .002 Nasal secretion total IgE, IU/mL 7.53 (5.64) 13.77 (21.46) 6.86 (5.03) 20.93 (41.78) 5.53 (4.05) –5.31 (4.31) –12.17 (–23.76, –0.57) .04 Serum TARC, pg/mL 506.20 (422.59) 384.19 (235.65) –125.80 (44.78) 506.77 (340.29) 288.94 (154.06) –204.62 (48.99) –78.82 (–183.10, 25.45) .135 Serum periostin, ng/mL 72.86 (28.52) 53.05 (18.76) –17.09 (7.52) 80.42 (24.44) 57.83 (22.27) –13.83 (6.53) 3.26 (–13.05, 19.57) .692 Nasal secretion periostin, ng/mL 6.92 (5.44) 8.37 (6.91) 0.64 (2.53) 7.27 (5.78) 4.26 (5.71) –2.96 (2.16) –3.60 (–7.60, 0.40) .076 Table E2 Inflammatory biomarker levels at baseline and change from baseline at week 16 in patients with CRSwNP and comorbid asthma</description><subject>Allergic rhinitis</subject><subject>Anosmia</subject><subject>Aspirin</subject><subject>Asthma</subject><subject>Atopic dermatitis</subject><subject>Biomarkers</subject><subject>CCL17 protein</subject><subject>Cell activation</subject><subject>Chemokines</subject><subject>Clinical outcomes</subject><subject>Comorbidity</subject><subject>Corticosteroids</subject><subject>Demography</subject><subject>Endoscopy</subject><subject>Immunoglobulin E</subject><subject>Immunotherapy</subject><subject>Inflammation</subject><subject>Interleukin 13</subject><subject>Interleukin 4</subject><subject>Interleukin 5</subject><subject>Leukocytes (eosinophilic)</subject><subject>Medicin och hälsovetenskap</subject><subject>Mental disorders</subject><subject>Mental health</subject><subject>Monoclonal antibodies</subject><subject>Nose</subject><subject>Olfaction</subject><subject>Pain</subject><subject>Pain perception</subject><subject>Patients</subject><subject>Polyps</subject><subject>Quality of life</subject><subject>Questionnaires</subject><subject>Respiratory tract</subject><subject>Respiratory tract diseases</subject><subject>Rhinitis</subject><subject>Sinusitis</subject><subject>Thymus</subject><issn>2213-2198</issn><issn>2213-2201</issn><issn>2213-2201</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>D8T</sourceid><recordid>eNp9kk2LFDEQhoMo7jLuH_AgAS9eus1Hd5IGL7LrFyx40XNIJ9VMxu5Om6R3WX-9aWZmBUFzSVH1vEXxViH0kpKaEireHuqD8UvNCO1qwmvC-BN0yRjlFSu5p-eYduoCXaV0IOUpKklDnqMLTjqmRKsu0a-bdfHjOpke-2mJ4Q4SXkz2MOcqwhJiBofDmm2YSsXP52LC9z7vsd3HMHuL497PIfl5TT77U202yYx4CePDkrCZHS49Quy9wybl_WReoGeDGRNcnf4d-v7xw7frz9Xt109frt_fVralIleODN1AoKFUMuGIUIIbaqxyklMBlreiGRrWDpK0FjohnWh6QSXfbBANcL5D1bFvuodl7fUS_WTigw7G61PqR4lAN4ooyQrf_ZMvDrk_orOQNlSqdjN8h94ctQX8uULKevLJwjiaGcKa9DaUpK1iqqCv_0IPYY1zcaJQqinDSCkLxY6UjSGlCMPjOJTo7RD0QW-HoLdD0ITrcghF9OrUeu0ncI-S89oL8O4IQPH9zkPUyZatWnA-gs3aBf-__r8B5YjGeQ</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Bachert, Claus</creator><creator>Hellings, Peter W.</creator><creator>Mullol, Joaquim</creator><creator>Naclerio, Robert M.</creator><creator>Chao, Jingdong</creator><creator>Amin, Nikhil</creator><creator>Grabher, Annette</creator><creator>Swanson, Brian N.</creator><creator>Hamilton, Jennifer D.</creator><creator>Guillonneau, Sophie</creator><creator>Taniou, Christine</creator><creator>Zhang, Donghui</creator><creator>Pirozzi, Gianluca</creator><creator>Graham, Neil M.H.</creator><creator>Staudinger, Heribert</creator><creator>Mannent, Leda P.</creator><creator>Khan, Asif</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20190901</creationdate><title>Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma</title><author>Bachert, Claus ; Hellings, Peter W. ; Mullol, Joaquim ; Naclerio, Robert M. ; Chao, Jingdong ; Amin, Nikhil ; Grabher, Annette ; Swanson, Brian N. ; Hamilton, Jennifer D. ; Guillonneau, Sophie ; Taniou, Christine ; Zhang, Donghui ; Pirozzi, Gianluca ; Graham, Neil M.H. ; Staudinger, Heribert ; Mannent, Leda P. ; Khan, Asif</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c516t-d0f9f0e411726d06863a1ac8d7316ec3564f425f705ce967d64b6173220164e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Allergic rhinitis</topic><topic>Anosmia</topic><topic>Aspirin</topic><topic>Asthma</topic><topic>Atopic dermatitis</topic><topic>Biomarkers</topic><topic>CCL17 protein</topic><topic>Cell activation</topic><topic>Chemokines</topic><topic>Clinical outcomes</topic><topic>Comorbidity</topic><topic>Corticosteroids</topic><topic>Demography</topic><topic>Endoscopy</topic><topic>Immunoglobulin E</topic><topic>Immunotherapy</topic><topic>Inflammation</topic><topic>Interleukin 13</topic><topic>Interleukin 4</topic><topic>Interleukin 5</topic><topic>Leukocytes (eosinophilic)</topic><topic>Medicin och hälsovetenskap</topic><topic>Mental disorders</topic><topic>Mental health</topic><topic>Monoclonal antibodies</topic><topic>Nose</topic><topic>Olfaction</topic><topic>Pain</topic><topic>Pain perception</topic><topic>Patients</topic><topic>Polyps</topic><topic>Quality of life</topic><topic>Questionnaires</topic><topic>Respiratory tract</topic><topic>Respiratory tract diseases</topic><topic>Rhinitis</topic><topic>Sinusitis</topic><topic>Thymus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bachert, Claus</creatorcontrib><creatorcontrib>Hellings, Peter W.</creatorcontrib><creatorcontrib>Mullol, Joaquim</creatorcontrib><creatorcontrib>Naclerio, Robert M.</creatorcontrib><creatorcontrib>Chao, Jingdong</creatorcontrib><creatorcontrib>Amin, Nikhil</creatorcontrib><creatorcontrib>Grabher, Annette</creatorcontrib><creatorcontrib>Swanson, Brian N.</creatorcontrib><creatorcontrib>Hamilton, Jennifer D.</creatorcontrib><creatorcontrib>Guillonneau, Sophie</creatorcontrib><creatorcontrib>Taniou, Christine</creatorcontrib><creatorcontrib>Zhang, Donghui</creatorcontrib><creatorcontrib>Pirozzi, Gianluca</creatorcontrib><creatorcontrib>Graham, Neil M.H.</creatorcontrib><creatorcontrib>Staudinger, Heribert</creatorcontrib><creatorcontrib>Mannent, Leda P.</creatorcontrib><creatorcontrib>Khan, Asif</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>The journal of allergy and clinical immunology in practice (Cambridge, MA)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bachert, Claus</au><au>Hellings, Peter W.</au><au>Mullol, Joaquim</au><au>Naclerio, Robert M.</au><au>Chao, Jingdong</au><au>Amin, Nikhil</au><au>Grabher, Annette</au><au>Swanson, Brian N.</au><au>Hamilton, Jennifer D.</au><au>Guillonneau, Sophie</au><au>Taniou, Christine</au><au>Zhang, Donghui</au><au>Pirozzi, Gianluca</au><au>Graham, Neil M.H.</au><au>Staudinger, Heribert</au><au>Mannent, Leda P.</au><au>Khan, Asif</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma</atitle><jtitle>The journal of allergy and clinical immunology in practice (Cambridge, MA)</jtitle><addtitle>J Allergy Clin Immunol Pract</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>7</volume><issue>7</issue><spage>2447</spage><epage>2449.e2</epage><pages>2447-2449.e2</pages><issn>2213-2198</issn><issn>2213-2201</issn><eissn>2213-2201</eissn><abstract>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory condition affecting the upper airways, with chronic symptoms such as nasal congestion, partial (hyposmia) or total (anosmia) loss of smell, anterior/posterior rhinorrhea, and mild facial pain.1 As many as 66% of patients with CRSwNP have comorbid asthma and suffer from more severe nasal obstruction, higher levels of lower airway inflammation, and worse asthma control than those without CRS.2,3 Thus, patients with CRSwNP and comorbid asthma have a high disease burden, seriously impacting health-related quality of life (HRQoL).2,3 Markers of type 2-mediated inflammation and antibody production (eg, IL-5, IgE) are associated with both CRSwNP and asthma pathogenesis.2 Dupilumab, a fully human VelocImmune-derived4,5 monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13, thus inhibiting signaling of both IL-4 and IL-13, key drivers of type 2 diseases such as atopic dermatitis, asthma, and allergic rhinitis.6 In a 16-week phase 2a study in adults with CRSwNP refractory to intranasal corticosteroids (INCS), adding dupilumab to mometasone furoate nasal spray (MFNS) reduced nasal polyp burden versus MFNS alone and significantly improved nasal congestion and airflow, sense of smell, HRQoL, and other nasal symptoms.7 We present a subgroup analysis of patients with CRSwNP and comorbid asthma from this study, examining the effect of dupilumab on patient-reported outcomes (PROs) for CRSwNP and asthma, and inflammatory biomarkers. EQ-5D VAS provides a simple measure of the patient's self-rated health on a vertical virtual analog scale, with scores 0 to 100 mm (worst-best imaginable health state).8 SF-36 comprises 8 domains assessing physical functioning, social functioning, role limitations due to physical and emotional problems, mental health, energy/vitality, bodily pain, and general health perception. Two summary scores, the physical (PCS) and mental health component summary, are calculated by the aggregation of the 8 SF-36 subscales, to evaluate the physical and mental health, respectively (higher scores indicating better HRQoL).9 The effects of dupilumab on the individual ACQ-5 scores (woken at night by asthma, awake in morning with asthma symptoms, limited in activities, shortness of breath, wheezing time), as well as inflammatory biomarkers (eosinophils, eosinophil cationic protein, thymus and activation-regulated chemokine, IgE, and periostin), were also assessed. [...]treatment with dupilumab was associated with an improvement of both clinical and patient-reported NP-specific outcomes, and asthma-specific outcomes in patients with CRSwNP and comorbid asthma.Acknowledgments Editorial assistance was provided by Bilge Yoruk, PhD, and Ravi Subramanian, PhD, of Excerpta Medica funded by Sanofi Genzyme and Regeneron Pharmaceuticals.Online Repository ACQ-5† Measure Mean score (SD) at baseline LS mean change (SE) from baseline to week 16 LS mean difference for dupilumab vs placebo (95% CI) Placebo/MFNS (n = 19) Dupilumab/MFNS (n = 16) Placebo/MFNS (n = 12) Dupilumab/MFNS (n = 15) Total overall‡ Total 1.63 (0.87) 1.55 (1.11) −0.10 (0.20) −1.19 (0.19) −1.09 (−1.54, −0.63)∗∗∗ Item 1§ Woken at night by asthma 1.00 (1.10) 0.88 (1.45) 0.08 (0.24) –0.91 (0.23) –0.99 (–1.55, –0.42)∗∗ Item 2§ Awake in morning with asthma symptoms 2.00 (1.37) 1.69 (1.25) 0.01 (0.22) –1.46 (0.20) –1.46 (–1.94, –0.99)∗∗∗ Item 3§ Limited in activities 1.38 (1.20) 1.25 (1.13) –0.11 (0.23) –0.93 (0.21) –0.83 (–1.34, –0.32)∗∗ Item 4§ Shortness of breath 2.19 (1.33) 1.94 (1.24) –0.29 (0.29) –1.33 (0.27) –1.04 (–1.77, –0.31)∗∗ Item 5§ Wheezing time 1.56 (0.63) 2.00 (1.90) –0.54 (0.36) –1.50 (0.34) –0.96 (–1.81, –0.12)∗ Table I ACQ-5 scores at baseline and change from baseline at week 16 in patients with CRSwNP and comorbid asthma Placebo/MFNS (n = 19) Dupilumab/MFNS (n = 16) Patient characteristic Age, mean (SD), y 47.7 (9.9) 51.4 (7.6) Male, n (%) 7 (36.8) 7 (43.8) Duration of CRSwNP, mean (SD), y 11.32 (8.93) 8.95 (6.33) Duration of asthma, mean (SD), y 20.15 (17.40) 15.46 (12.13) Patients with aspirin-sensitive asthma, n (%) 8 (42.1) 5 (31.3) Baseline measures of CRSwNP Nasal polyps endoscopic score, range 0-8∗, mean (SD) 5.53 (1.02) 5.94 (0.85) CT Lund-Mackay total score, range 0-24∗, mean (SD) 19.95 (5.65) 19.07 (4.23) CRSwNP disease severity VAS (0-10 cm)∗, mean (SD) 6.66 (2.36) 6.23 (2.73) Daily congestion/obstruction score (0-3)† 1.67 (0.74) 1.43 (0.73) Daily AM loss of smell score† (0-3)† 2.93 (0.24) 2.47 (0.96) SNOT-22 total score (0-110), mean (SD)∗ 43.63 (20.66) 40.63 (16.26) Baseline measures of asthma ACQ-5 total score, mean (SD) 1.63 (0.87) 1.55 (1.11) Baseline FEV1, mean (SD), % predicted 79.76 (14.55) 82.19 (17.71) Baseline levels of biomarkers Serum blood eosinophil count, mean (SD), 109/L 0.55 (0.83) 0.51 (0.25) Serum ECP, mean (SD), ng/mL 37.26 (48.33) 35.38 (26.27) Nasal secretion ECP, mean (SD), ng/mL 16.47 (11.49) 41.80 (43.44) Serum total IgE, mean (SD), IU/mL 233.06 (300.44) 167.13 (153.77) Nasal secretion total IgE, mean (SD), IU/mL 7.53 (5.64) 20.93 (41.78) Serum TARC, mean (SD), pg/mL 506.20 (422.59) 506.77 (340.29) Serum periostin, mean (SD), ng/mL 72.86 (28.52) 80.42 (24.44) Nasal secretion periostin, mean (SD), ng/mL 6.92 (5.44) 7.27 (5.78) Table E1 Baseline demographics and disease characteristics of patients with CRSwNP with comorbid asthma Biomarker Placebo/MFNS group (n = 19) Dupilumab/MFNS group (n = 16) LS mean difference for dupilumab vs placebo at week 16 (95% CI)∗ P value Baseline mean (SD) Week 16 mean (SD) LS mean change from baseline (SE) Baseline mean (SD) Week 16 mean (SD) LS mean change from baseline (SE) Serum blood eosinophil count, 109/L 0.55 (0.83) 0.37 (0.19) –0.15 (0.17) 0.51 (0.25) 0.53 (0.37) –0.06 (0.16) 0.09 (–0.34, 0.51) .682 Serum ECP, ng/mL 37.26 (48.33) 15.57 (11.92) –14.58 (9.83) 35.38 (26.27) 41.60 (47.60) 6.66 (9.77) 21.25 (–3.70, 46.20) .094 Nasal secretion ECP, ng/mL 16.47 (11.49) 29.08 (38.72) 26.47 (11.31) 41.80 (43.44) 39.07 (38.19) 16.92 (9.98) –9.55 (–35.89, 16.80) .472 Serum total IgE, IU/mL 233.06 (300.44) 128.87 (143.70) –38.09 (12.22) 167.13 (153.77) 102.07 (119.46) –86.59 (12.38) –48.49 (–78.66, –18.33) .002 Nasal secretion total IgE, IU/mL 7.53 (5.64) 13.77 (21.46) 6.86 (5.03) 20.93 (41.78) 5.53 (4.05) –5.31 (4.31) –12.17 (–23.76, –0.57) .04 Serum TARC, pg/mL 506.20 (422.59) 384.19 (235.65) –125.80 (44.78) 506.77 (340.29) 288.94 (154.06) –204.62 (48.99) –78.82 (–183.10, 25.45) .135 Serum periostin, ng/mL 72.86 (28.52) 53.05 (18.76) –17.09 (7.52) 80.42 (24.44) 57.83 (22.27) –13.83 (6.53) 3.26 (–13.05, 19.57) .692 Nasal secretion periostin, ng/mL 6.92 (5.44) 8.37 (6.91) 0.64 (2.53) 7.27 (5.78) 4.26 (5.71) –2.96 (2.16) –3.60 (–7.60, 0.40) .076 Table E2 Inflammatory biomarker levels at baseline and change from baseline at week 16 in patients with CRSwNP and comorbid asthma</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30928658</pmid><doi>10.1016/j.jaip.2019.03.023</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Allergic rhinitis Anosmia Aspirin Asthma Atopic dermatitis Biomarkers CCL17 protein Cell activation Chemokines Clinical outcomes Comorbidity Corticosteroids Demography Endoscopy Immunoglobulin E Immunotherapy Inflammation Interleukin 13 Interleukin 4 Interleukin 5 Leukocytes (eosinophilic) Medicin och hälsovetenskap Mental disorders Mental health Monoclonal antibodies Nose Olfaction Pain Pain perception Patients Polyps Quality of life Questionnaires Respiratory tract Respiratory tract diseases Rhinitis Sinusitis Thymus |
| title | Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma |
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