HLA-C06:02 Allele and Response to IL-12/23 Inhibition: Results from the Ustekinumab Phase 3 Psoriasis Program
Several small studies suggest that the presence of the human leukocyte antigen (HLA)-Cw6 (C*06:02) allele may be a predictor of improved response to ustekinumab. This study was designed to assess the association of the HLA-C*06:02 allele with response to ustekinumab in large cohorts of patients from...
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| Veröffentlicht in: | Journal of investigative dermatology 2016-12, Vol.136 (12), p.2364-2371 |
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| creator | Li, Katherine Huang, C. Chris Randazzo, Bruce Li, Shu Szapary, Philippe Curran, Mark Campbell, Kim Brodmerkel, Carrie |
| description | Several small studies suggest that the presence of the human leukocyte antigen (HLA)-Cw6 (C*06:02) allele may be a predictor of improved response to ustekinumab. This study was designed to assess the association of the HLA-C*06:02 allele with response to ustekinumab in large cohorts of patients from the phase 3 studies of ustekinumab in moderate-to-severe psoriasis. In this retrospective study, both HLA-C*06:02-positive and -negative patients demonstrated good responses to ustekinumab (86% vs. 76%, respectively, achieved at least a 75% improvement from baseline in Psoriasis Area and Severity Index [PASI 75] at week 24). A modestly higher proportion of HLA-C*06:02-positive than HLA-C*06:02-negative patients achieved PASI 75/90 responses at weeks 12 and 24. The largest response difference between the positive and negative patients (17.9%) was observed for PASI 75 (week 12), with smaller differences noted at later time points for PASI 90 (11.8% at week 24) and PASI 100 (10.2% at week 28). A differential response to ustekinumab has been confirmed in HLA-C*06:02-positive versus HLA-C*06:02-negative patients; however, this difference is modest, particularly at the higher response rate thresholds (PASI 90/100) and later time points (weeks 24/28). |
| doi_str_mv | 10.1016/j.jid.2016.06.631 |
| format | Article |
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Chris ; Randazzo, Bruce ; Li, Shu ; Szapary, Philippe ; Curran, Mark ; Campbell, Kim ; Brodmerkel, Carrie</creator><creatorcontrib>Li, Katherine ; Huang, C. Chris ; Randazzo, Bruce ; Li, Shu ; Szapary, Philippe ; Curran, Mark ; Campbell, Kim ; Brodmerkel, Carrie</creatorcontrib><description>Several small studies suggest that the presence of the human leukocyte antigen (HLA)-Cw6 (C*06:02) allele may be a predictor of improved response to ustekinumab. This study was designed to assess the association of the HLA-C*06:02 allele with response to ustekinumab in large cohorts of patients from the phase 3 studies of ustekinumab in moderate-to-severe psoriasis. In this retrospective study, both HLA-C*06:02-positive and -negative patients demonstrated good responses to ustekinumab (86% vs. 76%, respectively, achieved at least a 75% improvement from baseline in Psoriasis Area and Severity Index [PASI 75] at week 24). A modestly higher proportion of HLA-C*06:02-positive than HLA-C*06:02-negative patients achieved PASI 75/90 responses at weeks 12 and 24. The largest response difference between the positive and negative patients (17.9%) was observed for PASI 75 (week 12), with smaller differences noted at later time points for PASI 90 (11.8% at week 24) and PASI 100 (10.2% at week 28). A differential response to ustekinumab has been confirmed in HLA-C*06:02-positive versus HLA-C*06:02-negative patients; however, this difference is modest, particularly at the higher response rate thresholds (PASI 90/100) and later time points (weeks 24/28).</description><identifier>ISSN: 0022-202X</identifier><identifier>EISSN: 1523-1747</identifier><identifier>DOI: 10.1016/j.jid.2016.06.631</identifier><identifier>PMID: 27476722</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Age Factors ; Alleles ; Analysis of Variance ; Child ; Confidence Intervals ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug Administration Schedule ; Female ; HLA-C Antigens - drug effects ; HLA-C Antigens - genetics ; Humans ; Interleukin-23 - antagonists & inhibitors ; Interleukin-23 - immunology ; Male ; Molecular Targeted Therapy - methods ; Prognosis ; Psoriasis - drug therapy ; Psoriasis - genetics ; Psoriasis - immunology ; Risk Assessment ; Sex Factors ; Treatment Outcome ; Ustekinumab - therapeutic use ; Young Adult</subject><ispartof>Journal of investigative dermatology, 2016-12, Vol.136 (12), p.2364-2371</ispartof><rights>2016 The Authors</rights><rights>Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-61b28645c830a831856e8a77872164baf529cc126bbb32bf301dc2e271acd5d03</citedby><cites>FETCH-LOGICAL-c396t-61b28645c830a831856e8a77872164baf529cc126bbb32bf301dc2e271acd5d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27476722$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Katherine</creatorcontrib><creatorcontrib>Huang, C. Chris</creatorcontrib><creatorcontrib>Randazzo, Bruce</creatorcontrib><creatorcontrib>Li, Shu</creatorcontrib><creatorcontrib>Szapary, Philippe</creatorcontrib><creatorcontrib>Curran, Mark</creatorcontrib><creatorcontrib>Campbell, Kim</creatorcontrib><creatorcontrib>Brodmerkel, Carrie</creatorcontrib><title>HLA-C06:02 Allele and Response to IL-12/23 Inhibition: Results from the Ustekinumab Phase 3 Psoriasis Program</title><title>Journal of investigative dermatology</title><addtitle>J Invest Dermatol</addtitle><description>Several small studies suggest that the presence of the human leukocyte antigen (HLA)-Cw6 (C*06:02) allele may be a predictor of improved response to ustekinumab. This study was designed to assess the association of the HLA-C*06:02 allele with response to ustekinumab in large cohorts of patients from the phase 3 studies of ustekinumab in moderate-to-severe psoriasis. In this retrospective study, both HLA-C*06:02-positive and -negative patients demonstrated good responses to ustekinumab (86% vs. 76%, respectively, achieved at least a 75% improvement from baseline in Psoriasis Area and Severity Index [PASI 75] at week 24). A modestly higher proportion of HLA-C*06:02-positive than HLA-C*06:02-negative patients achieved PASI 75/90 responses at weeks 12 and 24. The largest response difference between the positive and negative patients (17.9%) was observed for PASI 75 (week 12), with smaller differences noted at later time points for PASI 90 (11.8% at week 24) and PASI 100 (10.2% at week 28). A differential response to ustekinumab has been confirmed in HLA-C*06:02-positive versus HLA-C*06:02-negative patients; however, this difference is modest, particularly at the higher response rate thresholds (PASI 90/100) and later time points (weeks 24/28).</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age Factors</subject><subject>Alleles</subject><subject>Analysis of Variance</subject><subject>Child</subject><subject>Confidence Intervals</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Drug Administration Schedule</subject><subject>Female</subject><subject>HLA-C Antigens - drug effects</subject><subject>HLA-C Antigens - genetics</subject><subject>Humans</subject><subject>Interleukin-23 - antagonists & inhibitors</subject><subject>Interleukin-23 - immunology</subject><subject>Male</subject><subject>Molecular Targeted Therapy - methods</subject><subject>Prognosis</subject><subject>Psoriasis - drug therapy</subject><subject>Psoriasis - genetics</subject><subject>Psoriasis - immunology</subject><subject>Risk Assessment</subject><subject>Sex Factors</subject><subject>Treatment Outcome</subject><subject>Ustekinumab - therapeutic use</subject><subject>Young Adult</subject><issn>0022-202X</issn><issn>1523-1747</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFu1DAQhi0EokvLA3BBPnJJ6hk3TracViugK63EqmolbpbtTFgvSbzYSSXevl5t4cjJI_n7f818jH0AUYIAdX0oD74tMY-lUKWS8IotoEJZQH1Tv2YLIRALFPjjgr1L6SAyeFM1b9kF5n9VIy7YcLddFWuhbgXyVd9TT9yMLb-ndAxjIj4FvtkWgNco-Wbce-snH8bbEzD3U-JdDAOf9sQf00S__DgPxvLd3uSo5LsUojfJJ76L4Wc0wxV705k-0fuX95I9fv3ysL4rtt-_bdarbeHkUk2FAotNXtU1UphGQlMpakxdNzXmC6zpKlw6B6istRJtJwW0DglrMK6tWiEv2adz7zGG3zOlSQ8-Oep7M1KYk4YGVS2XAJhROKMuhpQidfoY_WDiHw1Cnyzrg86W9cmyFkpnyznz8aV-tgO1_xJ_tWbg8xmgfOSTp6iT8zQ6an0kN-k2-P_UPwPWA4oR</recordid><startdate>201612</startdate><enddate>201612</enddate><creator>Li, Katherine</creator><creator>Huang, C. Chris</creator><creator>Randazzo, Bruce</creator><creator>Li, Shu</creator><creator>Szapary, Philippe</creator><creator>Curran, Mark</creator><creator>Campbell, Kim</creator><creator>Brodmerkel, Carrie</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201612</creationdate><title>HLA-C06:02 Allele and Response to IL-12/23 Inhibition: Results from the Ustekinumab Phase 3 Psoriasis Program</title><author>Li, Katherine ; Huang, C. Chris ; Randazzo, Bruce ; Li, Shu ; Szapary, Philippe ; Curran, Mark ; Campbell, Kim ; Brodmerkel, Carrie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-61b28645c830a831856e8a77872164baf529cc126bbb32bf301dc2e271acd5d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age Factors</topic><topic>Alleles</topic><topic>Analysis of Variance</topic><topic>Child</topic><topic>Confidence Intervals</topic><topic>Dose-Response Relationship, Drug</topic><topic>Double-Blind Method</topic><topic>Drug Administration Schedule</topic><topic>Female</topic><topic>HLA-C Antigens - drug effects</topic><topic>HLA-C Antigens - genetics</topic><topic>Humans</topic><topic>Interleukin-23 - antagonists & inhibitors</topic><topic>Interleukin-23 - immunology</topic><topic>Male</topic><topic>Molecular Targeted Therapy - methods</topic><topic>Prognosis</topic><topic>Psoriasis - drug therapy</topic><topic>Psoriasis - genetics</topic><topic>Psoriasis - immunology</topic><topic>Risk Assessment</topic><topic>Sex Factors</topic><topic>Treatment Outcome</topic><topic>Ustekinumab - therapeutic use</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Katherine</creatorcontrib><creatorcontrib>Huang, C. Chris</creatorcontrib><creatorcontrib>Randazzo, Bruce</creatorcontrib><creatorcontrib>Li, Shu</creatorcontrib><creatorcontrib>Szapary, Philippe</creatorcontrib><creatorcontrib>Curran, Mark</creatorcontrib><creatorcontrib>Campbell, Kim</creatorcontrib><creatorcontrib>Brodmerkel, Carrie</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of investigative dermatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Katherine</au><au>Huang, C. Chris</au><au>Randazzo, Bruce</au><au>Li, Shu</au><au>Szapary, Philippe</au><au>Curran, Mark</au><au>Campbell, Kim</au><au>Brodmerkel, Carrie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HLA-C06:02 Allele and Response to IL-12/23 Inhibition: Results from the Ustekinumab Phase 3 Psoriasis Program</atitle><jtitle>Journal of investigative dermatology</jtitle><addtitle>J Invest Dermatol</addtitle><date>2016-12</date><risdate>2016</risdate><volume>136</volume><issue>12</issue><spage>2364</spage><epage>2371</epage><pages>2364-2371</pages><issn>0022-202X</issn><eissn>1523-1747</eissn><abstract>Several small studies suggest that the presence of the human leukocyte antigen (HLA)-Cw6 (C*06:02) allele may be a predictor of improved response to ustekinumab. This study was designed to assess the association of the HLA-C*06:02 allele with response to ustekinumab in large cohorts of patients from the phase 3 studies of ustekinumab in moderate-to-severe psoriasis. In this retrospective study, both HLA-C*06:02-positive and -negative patients demonstrated good responses to ustekinumab (86% vs. 76%, respectively, achieved at least a 75% improvement from baseline in Psoriasis Area and Severity Index [PASI 75] at week 24). A modestly higher proportion of HLA-C*06:02-positive than HLA-C*06:02-negative patients achieved PASI 75/90 responses at weeks 12 and 24. The largest response difference between the positive and negative patients (17.9%) was observed for PASI 75 (week 12), with smaller differences noted at later time points for PASI 90 (11.8% at week 24) and PASI 100 (10.2% at week 28). A differential response to ustekinumab has been confirmed in HLA-C*06:02-positive versus HLA-C*06:02-negative patients; however, this difference is modest, particularly at the higher response rate thresholds (PASI 90/100) and later time points (weeks 24/28).</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27476722</pmid><doi>10.1016/j.jid.2016.06.631</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Age Factors Alleles Analysis of Variance Child Confidence Intervals Dose-Response Relationship, Drug Double-Blind Method Drug Administration Schedule Female HLA-C Antigens - drug effects HLA-C Antigens - genetics Humans Interleukin-23 - antagonists & inhibitors Interleukin-23 - immunology Male Molecular Targeted Therapy - methods Prognosis Psoriasis - drug therapy Psoriasis - genetics Psoriasis - immunology Risk Assessment Sex Factors Treatment Outcome Ustekinumab - therapeutic use Young Adult |
| title | HLA-C06:02 Allele and Response to IL-12/23 Inhibition: Results from the Ustekinumab Phase 3 Psoriasis Program |
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