Responder analysis using clinically meaningful thresholds: Post hoc analyses from randomized dupilumab clinical trials in patients with prurigo nodularis
Background Prurigo nodularis (PN) is an intensely pruritic disease characterized by itchy nodules on the trunk/extremities; it is often accompanied by skin pain and sleep disruption with negative impacts on the quality of life (QoL). The patient‐reported outcome (PRO) instruments, Worst Itch‐Numeric...
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| Veröffentlicht in: | Journal of the European Academy of Dermatology and Venereology 2024-10, Vol.38 (10), p.1965-1972 |
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| container_issue | 10 |
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| container_title | Journal of the European Academy of Dermatology and Venereology |
| container_volume | 38 |
| creator | Kwatra, Shawn G. Yosipovitch, Gil Ständer, Sonja Guillemin, Isabelle Msihid, Jérôme Bansal, Ashish Makhija, Melanie Wiggins, Simmi Zahn, Joseph Thomas, Ryan B. Bahloul, Donia |
| description | Background
Prurigo nodularis (PN) is an intensely pruritic disease characterized by itchy nodules on the trunk/extremities; it is often accompanied by skin pain and sleep disruption with negative impacts on the quality of life (QoL). The patient‐reported outcome (PRO) instruments, Worst Itch‐Numeric Rating Scale (WI‐NRS), Skin Pain‐NRS, Sleep‐NRS and Dermatology Life Quality Index (DLQI) have been psychometrically validated and the clinically meaningful within‐patient improvement thresholds (responder definition) have been established through data pooled from the two Phase‐3 trials (PRIME, NCT04183335 and PRIME2, NCT04202679) of dupilumab in adults with PN uncontrolled on topical therapies.
Objectives
To estimate the proportion of dupilumab‐treated patients (vs. placebo) achieving clinically meaningful improvement in itch, skin pain, sleep and QoL, either alone or in combination, from the data pooled from PRIME and PRIME2 trials.
Methods
The patient‐level data pooled from the two Phase‐3 trials (N = 311) were used for this post hoc analysis. Thresholds of clinically meaningful within‐patient improvement in PRO instrument scores from baseline at Week 24 used for defining responders were 4 (WI‐NRS and Skin Pain‐NRS), 2 (Sleep‐NRS) and 9 points (DLQI). The proportion of dupilumab‐treated patients, versus placebo, achieving the thresholds, and the time taken to achieve the thresholds were evaluated for the individual and combination of PROs.
Results
Responder rates were significantly higher with dupilumab, versus placebo at Week 24 for WI‐NRS (58.8% vs. 19.0%, p |
| doi_str_mv | 10.1111/jdv.20099 |
| format | Article |
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Prurigo nodularis (PN) is an intensely pruritic disease characterized by itchy nodules on the trunk/extremities; it is often accompanied by skin pain and sleep disruption with negative impacts on the quality of life (QoL). The patient‐reported outcome (PRO) instruments, Worst Itch‐Numeric Rating Scale (WI‐NRS), Skin Pain‐NRS, Sleep‐NRS and Dermatology Life Quality Index (DLQI) have been psychometrically validated and the clinically meaningful within‐patient improvement thresholds (responder definition) have been established through data pooled from the two Phase‐3 trials (PRIME, NCT04183335 and PRIME2, NCT04202679) of dupilumab in adults with PN uncontrolled on topical therapies.
Objectives
To estimate the proportion of dupilumab‐treated patients (vs. placebo) achieving clinically meaningful improvement in itch, skin pain, sleep and QoL, either alone or in combination, from the data pooled from PRIME and PRIME2 trials.
Methods
The patient‐level data pooled from the two Phase‐3 trials (N = 311) were used for this post hoc analysis. Thresholds of clinically meaningful within‐patient improvement in PRO instrument scores from baseline at Week 24 used for defining responders were 4 (WI‐NRS and Skin Pain‐NRS), 2 (Sleep‐NRS) and 9 points (DLQI). The proportion of dupilumab‐treated patients, versus placebo, achieving the thresholds, and the time taken to achieve the thresholds were evaluated for the individual and combination of PROs.
Results
Responder rates were significantly higher with dupilumab, versus placebo at Week 24 for WI‐NRS (58.8% vs. 19.0%, p < 0.0001), Skin Pain‐NRS (49.7% vs. 20.9%, p < 0.0001), Sleep‐NRS (42.5% vs. 23.4%, p < 0.0001) and DLQI (64.7% vs. 22.8%, p < 0.0001). Proportion of patients achieving simultaneous improvement in symptoms and QoL (24.8% vs. 6.3%, p < 0.0001) were significantly higher in dupilumab‐treated patients versus placebo. The time needed for achieving clinically meaningful improvement in symptoms were significantly lower in dupilumab‐treated patients, versus placebo.
Conclusions
Significantly greater proportion of dupilumab‐treated patients with PN, versus placebo, demonstrated clinically meaningful improvements in PRO measures of symptoms and QoL.</description><identifier>ISSN: 0926-9959</identifier><identifier>ISSN: 1468-3083</identifier><identifier>EISSN: 1468-3083</identifier><identifier>DOI: 10.1111/jdv.20099</identifier><identifier>PMID: 38785405</identifier><language>eng</language><publisher>England</publisher><ispartof>Journal of the European Academy of Dermatology and Venereology, 2024-10, Vol.38 (10), p.1965-1972</ispartof><rights>2024 Sanofi. published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.</rights><rights>2024 Sanofi. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3209-9ad0d8392be4121874b0b3c3b9490acd678fb37fb99c5ac888cadd9855706d0e3</cites><orcidid>0000-0003-3612-7786 ; 0000-0003-3736-1515 ; 0009-0008-9887-8159 ; 0000-0002-7371-6486</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjdv.20099$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjdv.20099$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38785405$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kwatra, Shawn G.</creatorcontrib><creatorcontrib>Yosipovitch, Gil</creatorcontrib><creatorcontrib>Ständer, Sonja</creatorcontrib><creatorcontrib>Guillemin, Isabelle</creatorcontrib><creatorcontrib>Msihid, Jérôme</creatorcontrib><creatorcontrib>Bansal, Ashish</creatorcontrib><creatorcontrib>Makhija, Melanie</creatorcontrib><creatorcontrib>Wiggins, Simmi</creatorcontrib><creatorcontrib>Zahn, Joseph</creatorcontrib><creatorcontrib>Thomas, Ryan B.</creatorcontrib><creatorcontrib>Bahloul, Donia</creatorcontrib><title>Responder analysis using clinically meaningful thresholds: Post hoc analyses from randomized dupilumab clinical trials in patients with prurigo nodularis</title><title>Journal of the European Academy of Dermatology and Venereology</title><addtitle>J Eur Acad Dermatol Venereol</addtitle><description>Background
Prurigo nodularis (PN) is an intensely pruritic disease characterized by itchy nodules on the trunk/extremities; it is often accompanied by skin pain and sleep disruption with negative impacts on the quality of life (QoL). The patient‐reported outcome (PRO) instruments, Worst Itch‐Numeric Rating Scale (WI‐NRS), Skin Pain‐NRS, Sleep‐NRS and Dermatology Life Quality Index (DLQI) have been psychometrically validated and the clinically meaningful within‐patient improvement thresholds (responder definition) have been established through data pooled from the two Phase‐3 trials (PRIME, NCT04183335 and PRIME2, NCT04202679) of dupilumab in adults with PN uncontrolled on topical therapies.
Objectives
To estimate the proportion of dupilumab‐treated patients (vs. placebo) achieving clinically meaningful improvement in itch, skin pain, sleep and QoL, either alone or in combination, from the data pooled from PRIME and PRIME2 trials.
Methods
The patient‐level data pooled from the two Phase‐3 trials (N = 311) were used for this post hoc analysis. Thresholds of clinically meaningful within‐patient improvement in PRO instrument scores from baseline at Week 24 used for defining responders were 4 (WI‐NRS and Skin Pain‐NRS), 2 (Sleep‐NRS) and 9 points (DLQI). The proportion of dupilumab‐treated patients, versus placebo, achieving the thresholds, and the time taken to achieve the thresholds were evaluated for the individual and combination of PROs.
Results
Responder rates were significantly higher with dupilumab, versus placebo at Week 24 for WI‐NRS (58.8% vs. 19.0%, p < 0.0001), Skin Pain‐NRS (49.7% vs. 20.9%, p < 0.0001), Sleep‐NRS (42.5% vs. 23.4%, p < 0.0001) and DLQI (64.7% vs. 22.8%, p < 0.0001). Proportion of patients achieving simultaneous improvement in symptoms and QoL (24.8% vs. 6.3%, p < 0.0001) were significantly higher in dupilumab‐treated patients versus placebo. The time needed for achieving clinically meaningful improvement in symptoms were significantly lower in dupilumab‐treated patients, versus placebo.
Conclusions
Significantly greater proportion of dupilumab‐treated patients with PN, versus placebo, demonstrated clinically meaningful improvements in PRO measures of symptoms and QoL.</description><issn>0926-9959</issn><issn>1468-3083</issn><issn>1468-3083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNp1kU1P3DAQhi0EKgvtgT-AfKSHwCTOh80NLYUWIRVVba-RYzuskWMHT1y0_JP-W9Luwo25jDR63ucwLyFHOZzm85w96D-nBYAQO2SRlzXPGHC2SxYgijoTohL75ADxAQDyvOIfyD7jDa9KqBbk7w-DY_DaRCq9dGu0SBNaf0-Vs94q6dyaDkb6-dQnR6dVNLgKTuM5vQs40VVQ26RB2scw0Ci9DoN9NprqNFqXBtm92egUrXRIraejnKzxE9InO63oGFO094H6oJOT0eJHstfPpPm03Yfk19WXn8uv2e3362_Li9tMsQJEJqQGzZkoOlPmRc6bsoOOKdaJUoBUum5437Gm74RQlVSccyW1FryqGqg1GHZITjbeMYbHZHBqB4vKOCe9CQlbBjWwpm6aYkY_b1AVA2I0fTtGO8i4bnNo_zXRzk20_5uY2eOtNnWD0W_k6-tn4GwDPFln1u-b2pvL3xvlC4wgl2c</recordid><startdate>202410</startdate><enddate>202410</enddate><creator>Kwatra, Shawn G.</creator><creator>Yosipovitch, Gil</creator><creator>Ständer, Sonja</creator><creator>Guillemin, Isabelle</creator><creator>Msihid, Jérôme</creator><creator>Bansal, Ashish</creator><creator>Makhija, Melanie</creator><creator>Wiggins, Simmi</creator><creator>Zahn, Joseph</creator><creator>Thomas, Ryan B.</creator><creator>Bahloul, Donia</creator><scope>24P</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3612-7786</orcidid><orcidid>https://orcid.org/0000-0003-3736-1515</orcidid><orcidid>https://orcid.org/0009-0008-9887-8159</orcidid><orcidid>https://orcid.org/0000-0002-7371-6486</orcidid></search><sort><creationdate>202410</creationdate><title>Responder analysis using clinically meaningful thresholds: Post hoc analyses from randomized dupilumab clinical trials in patients with prurigo nodularis</title><author>Kwatra, Shawn G. ; Yosipovitch, Gil ; Ständer, Sonja ; Guillemin, Isabelle ; Msihid, Jérôme ; Bansal, Ashish ; Makhija, Melanie ; Wiggins, Simmi ; Zahn, Joseph ; Thomas, Ryan B. ; Bahloul, Donia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3209-9ad0d8392be4121874b0b3c3b9490acd678fb37fb99c5ac888cadd9855706d0e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kwatra, Shawn G.</creatorcontrib><creatorcontrib>Yosipovitch, Gil</creatorcontrib><creatorcontrib>Ständer, Sonja</creatorcontrib><creatorcontrib>Guillemin, Isabelle</creatorcontrib><creatorcontrib>Msihid, Jérôme</creatorcontrib><creatorcontrib>Bansal, Ashish</creatorcontrib><creatorcontrib>Makhija, Melanie</creatorcontrib><creatorcontrib>Wiggins, Simmi</creatorcontrib><creatorcontrib>Zahn, Joseph</creatorcontrib><creatorcontrib>Thomas, Ryan B.</creatorcontrib><creatorcontrib>Bahloul, Donia</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the European Academy of Dermatology and Venereology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kwatra, Shawn G.</au><au>Yosipovitch, Gil</au><au>Ständer, Sonja</au><au>Guillemin, Isabelle</au><au>Msihid, Jérôme</au><au>Bansal, Ashish</au><au>Makhija, Melanie</au><au>Wiggins, Simmi</au><au>Zahn, Joseph</au><au>Thomas, Ryan B.</au><au>Bahloul, Donia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Responder analysis using clinically meaningful thresholds: Post hoc analyses from randomized dupilumab clinical trials in patients with prurigo nodularis</atitle><jtitle>Journal of the European Academy of Dermatology and Venereology</jtitle><addtitle>J Eur Acad Dermatol Venereol</addtitle><date>2024-10</date><risdate>2024</risdate><volume>38</volume><issue>10</issue><spage>1965</spage><epage>1972</epage><pages>1965-1972</pages><issn>0926-9959</issn><issn>1468-3083</issn><eissn>1468-3083</eissn><abstract>Background
Prurigo nodularis (PN) is an intensely pruritic disease characterized by itchy nodules on the trunk/extremities; it is often accompanied by skin pain and sleep disruption with negative impacts on the quality of life (QoL). The patient‐reported outcome (PRO) instruments, Worst Itch‐Numeric Rating Scale (WI‐NRS), Skin Pain‐NRS, Sleep‐NRS and Dermatology Life Quality Index (DLQI) have been psychometrically validated and the clinically meaningful within‐patient improvement thresholds (responder definition) have been established through data pooled from the two Phase‐3 trials (PRIME, NCT04183335 and PRIME2, NCT04202679) of dupilumab in adults with PN uncontrolled on topical therapies.
Objectives
To estimate the proportion of dupilumab‐treated patients (vs. placebo) achieving clinically meaningful improvement in itch, skin pain, sleep and QoL, either alone or in combination, from the data pooled from PRIME and PRIME2 trials.
Methods
The patient‐level data pooled from the two Phase‐3 trials (N = 311) were used for this post hoc analysis. Thresholds of clinically meaningful within‐patient improvement in PRO instrument scores from baseline at Week 24 used for defining responders were 4 (WI‐NRS and Skin Pain‐NRS), 2 (Sleep‐NRS) and 9 points (DLQI). The proportion of dupilumab‐treated patients, versus placebo, achieving the thresholds, and the time taken to achieve the thresholds were evaluated for the individual and combination of PROs.
Results
Responder rates were significantly higher with dupilumab, versus placebo at Week 24 for WI‐NRS (58.8% vs. 19.0%, p < 0.0001), Skin Pain‐NRS (49.7% vs. 20.9%, p < 0.0001), Sleep‐NRS (42.5% vs. 23.4%, p < 0.0001) and DLQI (64.7% vs. 22.8%, p < 0.0001). Proportion of patients achieving simultaneous improvement in symptoms and QoL (24.8% vs. 6.3%, p < 0.0001) were significantly higher in dupilumab‐treated patients versus placebo. The time needed for achieving clinically meaningful improvement in symptoms were significantly lower in dupilumab‐treated patients, versus placebo.
Conclusions
Significantly greater proportion of dupilumab‐treated patients with PN, versus placebo, demonstrated clinically meaningful improvements in PRO measures of symptoms and QoL.</abstract><cop>England</cop><pmid>38785405</pmid><doi>10.1111/jdv.20099</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-3612-7786</orcidid><orcidid>https://orcid.org/0000-0003-3736-1515</orcidid><orcidid>https://orcid.org/0009-0008-9887-8159</orcidid><orcidid>https://orcid.org/0000-0002-7371-6486</orcidid><oa>free_for_read</oa></addata></record> |
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| title | Responder analysis using clinically meaningful thresholds: Post hoc analyses from randomized dupilumab clinical trials in patients with prurigo nodularis |
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