Guselkumab (an IL-23–specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis
Background IL-23 expression is increased in psoriatic lesions and might regulate TH 17 T-cell counts in patients with psoriasis. Objectives We sought to test a novel IL-23–specific therapeutic agent for the treatment of psoriasis. Methods In this randomized, double-blind, placebo-controlled study th...
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| Veröffentlicht in: | Journal of allergy and clinical immunology 2014-04, Vol.133 (4), p.1032-1040 |
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| creator | Sofen, Howard, MD Smith, Stacy, MD Matheson, Robert T., MD Leonardi, Craig L., MD Calderon, Cesar, PhD Brodmerkel, Carrie, PhD Li, Katherine, MS Campbell, Kim, PhD Marciniak, Stanley J., MBA Wasfi, Yasmine, MD, PhD Wang, Yuhua, PhD Szapary, Philippe, MD Krueger, James G., MD, PhD |
| description | Background IL-23 expression is increased in psoriatic lesions and might regulate TH 17 T-cell counts in patients with psoriasis. Objectives We sought to test a novel IL-23–specific therapeutic agent for the treatment of psoriasis. Methods In this randomized, double-blind, placebo-controlled study the safety, tolerability, and clinical response of guselkumab, an anti–IL-23–specific mAb, were evaluated in patients with moderate-to-severe plaque psoriasis. A total of 24 patients were randomized to receive a single dose of placebo or 10, 30, 100, or 300 mg of guselkumab. Clinical response was assessed by using the Psoriasis Area and Severity Index (PASI). Additionally, histologic analysis and gene expression in skin biopsy specimens from guselkumab-treated patients were compared with those from placebo-treated patients. Results At week 12, 50% (10 mg), 60% (30 and 100 mg), and 100% (300 mg) of guselkumab-treated patients, respectively, achieved a 75% improvement in PASI scores from baseline compared with 0% of placebo-treated patients. Improvements in PASI scores were generally maintained through week 24 in all guselkumab-treated patients. The proportion of patients experiencing an adverse event was comparable between the combined guselkumab (13/20 [65.0%]) and placebo (2/4 [50.0%]) groups through week 24. Analysis of lesional and nonlesional skin biopsy specimens demonstrated decreases in epidermal thickness and T-cell and dendritic cell expression in guselkumab-treated patients compared with values seen in placebo-treated patients. At week 12, significant reductions in psoriasis gene expression and serum IL-17A levels were observed in guselkumab-treated patients. Conclusion IL-23 inhibition with a single dose of guselkumab results in clinical responses in patients with moderate-to-severe psoriasis, suggesting that neutralization of IL-23 alone is a promising therapy for psoriasis. |
| doi_str_mv | 10.1016/j.jaci.2014.01.025 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1566840076</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S009167491400181X</els_id><sourcerecordid>3556008911</sourcerecordid><originalsourceid>FETCH-LOGICAL-c546t-7c4fdab7dd3a49eadb5df542f093ec3800aef93166d3e5ba31e8ace5a5aa96983</originalsourceid><addsrcrecordid>eNqNkt-K1TAQh4so7nH1BbyQgAjrRWvSpmkDIiyLrgsHvFDBuzBNppiz_WemXdkrfQff0Ccx5Zx1YS_EqxD4fjOZ-ZIkTwXPBBfq1S7bgfVZzoXMuMh4Xt5LNoLrKlV1Xt5PNpxrkapK6qPkEdGOx3tR64fJUS5VpaXSm-TH-ULYXS49NOwEBnaxTfPi989fNKH1rbesP21eMof9ONAcYEZitvODt9AxGBzrxw7t0kFgAWmKEDI_sAlmj8NM7Lufv0bG4RpN5zElvMKAbKIxeCBPj5MHLXSETw7ncfL53dtPZ-_T7Yfzi7PTbWpLqea0srJ10FTOFSA1gmtK15Yyb-NEaIuac8BWF0IpV2DZQCGwBosllABa6bo4Tk72dacwfluQZtN7sth1MOC4kBGlUrXkvFL_gQpR53leyIg-v4PuxiUMcRAjlJRVVWm-9s73lA0jUcDWTMH3EK6N4GY1aXZmNWlWk4YLE03G0LND6aXp0f2N3KiLwIsDABRttAEG6-mWq2N_LnnkXu85jOu98hgM2SjHovMB7Wzc6P_9jjd34jf-L_Ea6XZeQ7nh5uP659YvJ-IyRS2-FH8Az6PS_Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1644777908</pqid></control><display><type>article</type><title>Guselkumab (an IL-23–specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Sofen, Howard, MD ; Smith, Stacy, MD ; Matheson, Robert T., MD ; Leonardi, Craig L., MD ; Calderon, Cesar, PhD ; Brodmerkel, Carrie, PhD ; Li, Katherine, MS ; Campbell, Kim, PhD ; Marciniak, Stanley J., MBA ; Wasfi, Yasmine, MD, PhD ; Wang, Yuhua, PhD ; Szapary, Philippe, MD ; Krueger, James G., MD, PhD</creator><creatorcontrib>Sofen, Howard, MD ; Smith, Stacy, MD ; Matheson, Robert T., MD ; Leonardi, Craig L., MD ; Calderon, Cesar, PhD ; Brodmerkel, Carrie, PhD ; Li, Katherine, MS ; Campbell, Kim, PhD ; Marciniak, Stanley J., MBA ; Wasfi, Yasmine, MD, PhD ; Wang, Yuhua, PhD ; Szapary, Philippe, MD ; Krueger, James G., MD, PhD</creatorcontrib><description>Background IL-23 expression is increased in psoriatic lesions and might regulate TH 17 T-cell counts in patients with psoriasis. Objectives We sought to test a novel IL-23–specific therapeutic agent for the treatment of psoriasis. Methods In this randomized, double-blind, placebo-controlled study the safety, tolerability, and clinical response of guselkumab, an anti–IL-23–specific mAb, were evaluated in patients with moderate-to-severe plaque psoriasis. A total of 24 patients were randomized to receive a single dose of placebo or 10, 30, 100, or 300 mg of guselkumab. Clinical response was assessed by using the Psoriasis Area and Severity Index (PASI). Additionally, histologic analysis and gene expression in skin biopsy specimens from guselkumab-treated patients were compared with those from placebo-treated patients. Results At week 12, 50% (10 mg), 60% (30 and 100 mg), and 100% (300 mg) of guselkumab-treated patients, respectively, achieved a 75% improvement in PASI scores from baseline compared with 0% of placebo-treated patients. Improvements in PASI scores were generally maintained through week 24 in all guselkumab-treated patients. The proportion of patients experiencing an adverse event was comparable between the combined guselkumab (13/20 [65.0%]) and placebo (2/4 [50.0%]) groups through week 24. Analysis of lesional and nonlesional skin biopsy specimens demonstrated decreases in epidermal thickness and T-cell and dendritic cell expression in guselkumab-treated patients compared with values seen in placebo-treated patients. At week 12, significant reductions in psoriasis gene expression and serum IL-17A levels were observed in guselkumab-treated patients. Conclusion IL-23 inhibition with a single dose of guselkumab results in clinical responses in patients with moderate-to-severe psoriasis, suggesting that neutralization of IL-23 alone is a promising therapy for psoriasis.</description><identifier>ISSN: 0091-6749</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1016/j.jaci.2014.01.025</identifier><identifier>PMID: 24679469</identifier><identifier>CODEN: JACIBY</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Allergy and Immunology ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Neutralizing - administration & dosage ; Antibodies, Neutralizing - adverse effects ; Antibodies, Neutralizing - therapeutic use ; Biological and medical sciences ; Biomarkers ; Biopsy ; Cluster Analysis ; Cytokines ; Cytokines - blood ; Cytokines - metabolism ; Dermatology ; Disease ; Drug therapy ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gene expression ; Gene Expression Profiling ; guselkumab ; Histology ; Humans ; Hypothesis testing ; IL-23 ; Immunopathology ; Inflammation Mediators - blood ; Inflammation Mediators - metabolism ; Interleukin-17 - blood ; Interleukin-23 - antagonists & inhibitors ; Lymphocytes ; Medical sciences ; Patients ; Proteins ; Psoriasis ; Psoriasis - drug therapy ; Psoriasis - genetics ; Psoriasis - immunology ; Psoriasis - metabolism ; Psoriasis - pathology ; Psoriasis Area and Severity Index ; Psoriasis. Parapsoriasis. Lichen ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ; serum ; skin ; Skin - immunology ; Skin - pathology ; Statistical methods ; Studies ; T cell ; TH17 ; Th17 Cells - immunology ; Th17 Cells - metabolism ; Treatment Outcome</subject><ispartof>Journal of allergy and clinical immunology, 2014-04, Vol.133 (4), p.1032-1040</ispartof><rights>The Authors</rights><rights>2014 The Authors</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Apr 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c546t-7c4fdab7dd3a49eadb5df542f093ec3800aef93166d3e5ba31e8ace5a5aa96983</citedby><cites>FETCH-LOGICAL-c546t-7c4fdab7dd3a49eadb5df542f093ec3800aef93166d3e5ba31e8ace5a5aa96983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S009167491400181X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28447040$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24679469$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sofen, Howard, MD</creatorcontrib><creatorcontrib>Smith, Stacy, MD</creatorcontrib><creatorcontrib>Matheson, Robert T., MD</creatorcontrib><creatorcontrib>Leonardi, Craig L., MD</creatorcontrib><creatorcontrib>Calderon, Cesar, PhD</creatorcontrib><creatorcontrib>Brodmerkel, Carrie, PhD</creatorcontrib><creatorcontrib>Li, Katherine, MS</creatorcontrib><creatorcontrib>Campbell, Kim, PhD</creatorcontrib><creatorcontrib>Marciniak, Stanley J., MBA</creatorcontrib><creatorcontrib>Wasfi, Yasmine, MD, PhD</creatorcontrib><creatorcontrib>Wang, Yuhua, PhD</creatorcontrib><creatorcontrib>Szapary, Philippe, MD</creatorcontrib><creatorcontrib>Krueger, James G., MD, PhD</creatorcontrib><title>Guselkumab (an IL-23–specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis</title><title>Journal of allergy and clinical immunology</title><addtitle>J Allergy Clin Immunol</addtitle><description>Background IL-23 expression is increased in psoriatic lesions and might regulate TH 17 T-cell counts in patients with psoriasis. Objectives We sought to test a novel IL-23–specific therapeutic agent for the treatment of psoriasis. Methods In this randomized, double-blind, placebo-controlled study the safety, tolerability, and clinical response of guselkumab, an anti–IL-23–specific mAb, were evaluated in patients with moderate-to-severe plaque psoriasis. A total of 24 patients were randomized to receive a single dose of placebo or 10, 30, 100, or 300 mg of guselkumab. Clinical response was assessed by using the Psoriasis Area and Severity Index (PASI). Additionally, histologic analysis and gene expression in skin biopsy specimens from guselkumab-treated patients were compared with those from placebo-treated patients. Results At week 12, 50% (10 mg), 60% (30 and 100 mg), and 100% (300 mg) of guselkumab-treated patients, respectively, achieved a 75% improvement in PASI scores from baseline compared with 0% of placebo-treated patients. Improvements in PASI scores were generally maintained through week 24 in all guselkumab-treated patients. The proportion of patients experiencing an adverse event was comparable between the combined guselkumab (13/20 [65.0%]) and placebo (2/4 [50.0%]) groups through week 24. Analysis of lesional and nonlesional skin biopsy specimens demonstrated decreases in epidermal thickness and T-cell and dendritic cell expression in guselkumab-treated patients compared with values seen in placebo-treated patients. At week 12, significant reductions in psoriasis gene expression and serum IL-17A levels were observed in guselkumab-treated patients. Conclusion IL-23 inhibition with a single dose of guselkumab results in clinical responses in patients with moderate-to-severe psoriasis, suggesting that neutralization of IL-23 alone is a promising therapy for psoriasis.</description><subject>Allergy and Immunology</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antibodies, Neutralizing - administration & dosage</subject><subject>Antibodies, Neutralizing - adverse effects</subject><subject>Antibodies, Neutralizing - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Biopsy</subject><subject>Cluster Analysis</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Cytokines - metabolism</subject><subject>Dermatology</subject><subject>Disease</subject><subject>Drug therapy</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>guselkumab</subject><subject>Histology</subject><subject>Humans</subject><subject>Hypothesis testing</subject><subject>IL-23</subject><subject>Immunopathology</subject><subject>Inflammation Mediators - blood</subject><subject>Inflammation Mediators - metabolism</subject><subject>Interleukin-17 - blood</subject><subject>Interleukin-23 - antagonists & inhibitors</subject><subject>Lymphocytes</subject><subject>Medical sciences</subject><subject>Patients</subject><subject>Proteins</subject><subject>Psoriasis</subject><subject>Psoriasis - drug therapy</subject><subject>Psoriasis - genetics</subject><subject>Psoriasis - immunology</subject><subject>Psoriasis - metabolism</subject><subject>Psoriasis - pathology</subject><subject>Psoriasis Area and Severity Index</subject><subject>Psoriasis. Parapsoriasis. Lichen</subject><subject>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><subject>serum</subject><subject>skin</subject><subject>Skin - immunology</subject><subject>Skin - pathology</subject><subject>Statistical methods</subject><subject>Studies</subject><subject>T cell</subject><subject>TH17</subject><subject>Th17 Cells - immunology</subject><subject>Th17 Cells - metabolism</subject><subject>Treatment Outcome</subject><issn>0091-6749</issn><issn>1097-6825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkt-K1TAQh4so7nH1BbyQgAjrRWvSpmkDIiyLrgsHvFDBuzBNppiz_WemXdkrfQff0Ccx5Zx1YS_EqxD4fjOZ-ZIkTwXPBBfq1S7bgfVZzoXMuMh4Xt5LNoLrKlV1Xt5PNpxrkapK6qPkEdGOx3tR64fJUS5VpaXSm-TH-ULYXS49NOwEBnaxTfPi989fNKH1rbesP21eMof9ONAcYEZitvODt9AxGBzrxw7t0kFgAWmKEDI_sAlmj8NM7Lufv0bG4RpN5zElvMKAbKIxeCBPj5MHLXSETw7ncfL53dtPZ-_T7Yfzi7PTbWpLqea0srJ10FTOFSA1gmtK15Yyb-NEaIuac8BWF0IpV2DZQCGwBosllABa6bo4Tk72dacwfluQZtN7sth1MOC4kBGlUrXkvFL_gQpR53leyIg-v4PuxiUMcRAjlJRVVWm-9s73lA0jUcDWTMH3EK6N4GY1aXZmNWlWk4YLE03G0LND6aXp0f2N3KiLwIsDABRttAEG6-mWq2N_LnnkXu85jOu98hgM2SjHovMB7Wzc6P_9jjd34jf-L_Ea6XZeQ7nh5uP659YvJ-IyRS2-FH8Az6PS_Q</recordid><startdate>20140401</startdate><enddate>20140401</enddate><creator>Sofen, Howard, MD</creator><creator>Smith, Stacy, MD</creator><creator>Matheson, Robert T., MD</creator><creator>Leonardi, Craig L., MD</creator><creator>Calderon, Cesar, PhD</creator><creator>Brodmerkel, Carrie, PhD</creator><creator>Li, Katherine, MS</creator><creator>Campbell, Kim, PhD</creator><creator>Marciniak, Stanley J., MBA</creator><creator>Wasfi, Yasmine, MD, PhD</creator><creator>Wang, Yuhua, PhD</creator><creator>Szapary, Philippe, MD</creator><creator>Krueger, James G., MD, PhD</creator><general>Elsevier Inc</general><general>Elsevier</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</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>7SS</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20140401</creationdate><title>Guselkumab (an IL-23–specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis</title><author>Sofen, Howard, MD ; Smith, Stacy, MD ; Matheson, Robert T., MD ; Leonardi, Craig L., MD ; Calderon, Cesar, PhD ; Brodmerkel, Carrie, PhD ; Li, Katherine, MS ; Campbell, Kim, PhD ; Marciniak, Stanley J., MBA ; Wasfi, Yasmine, MD, PhD ; Wang, Yuhua, PhD ; Szapary, Philippe, MD ; Krueger, James G., MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c546t-7c4fdab7dd3a49eadb5df542f093ec3800aef93166d3e5ba31e8ace5a5aa96983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Allergy and Immunology</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antibodies, Neutralizing - administration & dosage</topic><topic>Antibodies, Neutralizing - adverse effects</topic><topic>Antibodies, Neutralizing - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Biopsy</topic><topic>Cluster Analysis</topic><topic>Cytokines</topic><topic>Cytokines - blood</topic><topic>Cytokines - metabolism</topic><topic>Dermatology</topic><topic>Disease</topic><topic>Drug therapy</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>guselkumab</topic><topic>Histology</topic><topic>Humans</topic><topic>Hypothesis testing</topic><topic>IL-23</topic><topic>Immunopathology</topic><topic>Inflammation Mediators - blood</topic><topic>Inflammation Mediators - metabolism</topic><topic>Interleukin-17 - blood</topic><topic>Interleukin-23 - antagonists & inhibitors</topic><topic>Lymphocytes</topic><topic>Medical sciences</topic><topic>Patients</topic><topic>Proteins</topic><topic>Psoriasis</topic><topic>Psoriasis - drug therapy</topic><topic>Psoriasis - genetics</topic><topic>Psoriasis - immunology</topic><topic>Psoriasis - metabolism</topic><topic>Psoriasis - pathology</topic><topic>Psoriasis Area and Severity Index</topic><topic>Psoriasis. Parapsoriasis. Lichen</topic><topic>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</topic><topic>serum</topic><topic>skin</topic><topic>Skin - immunology</topic><topic>Skin - pathology</topic><topic>Statistical methods</topic><topic>Studies</topic><topic>T cell</topic><topic>TH17</topic><topic>Th17 Cells - immunology</topic><topic>Th17 Cells - metabolism</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sofen, Howard, MD</creatorcontrib><creatorcontrib>Smith, Stacy, MD</creatorcontrib><creatorcontrib>Matheson, Robert T., MD</creatorcontrib><creatorcontrib>Leonardi, Craig L., MD</creatorcontrib><creatorcontrib>Calderon, Cesar, PhD</creatorcontrib><creatorcontrib>Brodmerkel, Carrie, PhD</creatorcontrib><creatorcontrib>Li, Katherine, MS</creatorcontrib><creatorcontrib>Campbell, Kim, PhD</creatorcontrib><creatorcontrib>Marciniak, Stanley J., MBA</creatorcontrib><creatorcontrib>Wasfi, Yasmine, MD, PhD</creatorcontrib><creatorcontrib>Wang, Yuhua, PhD</creatorcontrib><creatorcontrib>Szapary, Philippe, MD</creatorcontrib><creatorcontrib>Krueger, James G., MD, PhD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of allergy and clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sofen, Howard, MD</au><au>Smith, Stacy, MD</au><au>Matheson, Robert T., MD</au><au>Leonardi, Craig L., MD</au><au>Calderon, Cesar, PhD</au><au>Brodmerkel, Carrie, PhD</au><au>Li, Katherine, MS</au><au>Campbell, Kim, PhD</au><au>Marciniak, Stanley J., MBA</au><au>Wasfi, Yasmine, MD, PhD</au><au>Wang, Yuhua, PhD</au><au>Szapary, Philippe, MD</au><au>Krueger, James G., MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Guselkumab (an IL-23–specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis</atitle><jtitle>Journal of allergy and clinical immunology</jtitle><addtitle>J Allergy Clin Immunol</addtitle><date>2014-04-01</date><risdate>2014</risdate><volume>133</volume><issue>4</issue><spage>1032</spage><epage>1040</epage><pages>1032-1040</pages><issn>0091-6749</issn><eissn>1097-6825</eissn><coden>JACIBY</coden><abstract>Background IL-23 expression is increased in psoriatic lesions and might regulate TH 17 T-cell counts in patients with psoriasis. Objectives We sought to test a novel IL-23–specific therapeutic agent for the treatment of psoriasis. Methods In this randomized, double-blind, placebo-controlled study the safety, tolerability, and clinical response of guselkumab, an anti–IL-23–specific mAb, were evaluated in patients with moderate-to-severe plaque psoriasis. A total of 24 patients were randomized to receive a single dose of placebo or 10, 30, 100, or 300 mg of guselkumab. Clinical response was assessed by using the Psoriasis Area and Severity Index (PASI). Additionally, histologic analysis and gene expression in skin biopsy specimens from guselkumab-treated patients were compared with those from placebo-treated patients. Results At week 12, 50% (10 mg), 60% (30 and 100 mg), and 100% (300 mg) of guselkumab-treated patients, respectively, achieved a 75% improvement in PASI scores from baseline compared with 0% of placebo-treated patients. Improvements in PASI scores were generally maintained through week 24 in all guselkumab-treated patients. The proportion of patients experiencing an adverse event was comparable between the combined guselkumab (13/20 [65.0%]) and placebo (2/4 [50.0%]) groups through week 24. Analysis of lesional and nonlesional skin biopsy specimens demonstrated decreases in epidermal thickness and T-cell and dendritic cell expression in guselkumab-treated patients compared with values seen in placebo-treated patients. At week 12, significant reductions in psoriasis gene expression and serum IL-17A levels were observed in guselkumab-treated patients. Conclusion IL-23 inhibition with a single dose of guselkumab results in clinical responses in patients with moderate-to-severe psoriasis, suggesting that neutralization of IL-23 alone is a promising therapy for psoriasis.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>24679469</pmid><doi>10.1016/j.jaci.2014.01.025</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Allergy and Immunology Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - therapeutic use Antibodies, Neutralizing - administration & dosage Antibodies, Neutralizing - adverse effects Antibodies, Neutralizing - therapeutic use Biological and medical sciences Biomarkers Biopsy Cluster Analysis Cytokines Cytokines - blood Cytokines - metabolism Dermatology Disease Drug therapy Fundamental and applied biological sciences. Psychology Fundamental immunology Gene expression Gene Expression Profiling guselkumab Histology Humans Hypothesis testing IL-23 Immunopathology Inflammation Mediators - blood Inflammation Mediators - metabolism Interleukin-17 - blood Interleukin-23 - antagonists & inhibitors Lymphocytes Medical sciences Patients Proteins Psoriasis Psoriasis - drug therapy Psoriasis - genetics Psoriasis - immunology Psoriasis - metabolism Psoriasis - pathology Psoriasis Area and Severity Index Psoriasis. Parapsoriasis. Lichen Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis serum skin Skin - immunology Skin - pathology Statistical methods Studies T cell TH17 Th17 Cells - immunology Th17 Cells - metabolism Treatment Outcome |
| title | Guselkumab (an IL-23–specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T23%3A19%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Guselkumab%20(an%20IL-23%E2%80%93specific%20mAb)%20demonstrates%20clinical%20and%20molecular%20response%20in%20patients%20with%20moderate-to-severe%20psoriasis&rft.jtitle=Journal%20of%20allergy%20and%20clinical%20immunology&rft.au=Sofen,%20Howard,%20MD&rft.date=2014-04-01&rft.volume=133&rft.issue=4&rft.spage=1032&rft.epage=1040&rft.pages=1032-1040&rft.issn=0091-6749&rft.eissn=1097-6825&rft.coden=JACIBY&rft_id=info:doi/10.1016/j.jaci.2014.01.025&rft_dat=%3Cproquest_cross%3E3556008911%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1644777908&rft_id=info:pmid/24679469&rft_els_id=S009167491400181X&rfr_iscdi=true |