Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double‐blind, phase III NAVIGATE trial

Summary Background Guselkumab, an anti‐interleukin‐23 monoclonal antibody, has demonstrated significant efficacy in phase III psoriasis trials. Objectives To evaluate the efficacy and safety of guselkumab in patients with moderate‐to‐severe plaque psoriasis who had an inadequate response to ustekinu...

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Veröffentlicht in:British journal of dermatology (1951) 2018-01, Vol.178 (1), p.114-123
Hauptverfasser: Langley, R.G., Tsai, T.‐F., Flavin, S., Song, M., Randazzo, B., Wasfi, Y., Jiang, J., Li, S., Puig, L.
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container_issue 1
container_start_page 114
container_title British journal of dermatology (1951)
container_volume 178
creator Langley, R.G.
Tsai, T.‐F.
Flavin, S.
Song, M.
Randazzo, B.
Wasfi, Y.
Jiang, J.
Li, S.
Puig, L.
description Summary Background Guselkumab, an anti‐interleukin‐23 monoclonal antibody, has demonstrated significant efficacy in phase III psoriasis trials. Objectives To evaluate the efficacy and safety of guselkumab in patients with moderate‐to‐severe plaque psoriasis who had an inadequate response to ustekinumab. Methods In this phase III, randomized, double‐blind study, 871 patients received open‐label ustekinumab (45 mg or 90 mg) at weeks 0 and 4. At week 16, 268 patients with an inadequate response to ustekinumab [Investigator's Global Assessment (IGA) ≥ 2] were randomized (double‐blind) to guselkumab 100 mg or to continue ustekinumab; 585 of 871 patients (67%) with IGA 0/1 at week 16 continued open‐label ustekinumab. The primary end point was the number of visits at which randomized patients achieved IGA 0/1 and at least a two‐grade improvement (from week 16) from week 28 to week 40. Improvement ≥ 90% or 100% in Psoriasis Area and Severity Index (PASI 90/100) and Dermatology Life Quality Index (DLQI) of 0/1 were also assessed. Results The mean number of visits at which patients achieved IGA 0/1 and at least a two‐grade improvemen (week 28–40) was significantly greater in the guselkumab group vs. the randomized ustekinumab group (1·5 vs. 0·7; P 
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Objectives To evaluate the efficacy and safety of guselkumab in patients with moderate‐to‐severe plaque psoriasis who had an inadequate response to ustekinumab. Methods In this phase III, randomized, double‐blind study, 871 patients received open‐label ustekinumab (45 mg or 90 mg) at weeks 0 and 4. At week 16, 268 patients with an inadequate response to ustekinumab [Investigator's Global Assessment (IGA) ≥ 2] were randomized (double‐blind) to guselkumab 100 mg or to continue ustekinumab; 585 of 871 patients (67%) with IGA 0/1 at week 16 continued open‐label ustekinumab. The primary end point was the number of visits at which randomized patients achieved IGA 0/1 and at least a two‐grade improvement (from week 16) from week 28 to week 40. Improvement ≥ 90% or 100% in Psoriasis Area and Severity Index (PASI 90/100) and Dermatology Life Quality Index (DLQI) of 0/1 were also assessed. Results The mean number of visits at which patients achieved IGA 0/1 and at least a two‐grade improvemen (week 28–40) was significantly greater in the guselkumab group vs. the randomized ustekinumab group (1·5 vs. 0·7; P &lt; 0·001); greater proportions of patients in the guselkumab group achieved IGA 0/1 and at least a two‐grade improvement at week 28 (31·1% vs. 14·3%; P = 0·001) and week 52 (36·3% vs. 17·3%; P &lt; 0·001). Greater proportions of patients treated with guselkumab achieved PASI 90, PASI 100 and DLQI 0/1 at week 52. After week 16, 64·4% of patients in the guselkumab group and 55·6% in the ustekinumab group had at least one adverse event (AE); infections were the most frequent AE type. Overall, 6·7% (n = 9) of patients in the guselkumab group had at least one serious AE compared with 4·5% (n = 6) for the ustekinumab group. Conclusions Patients treated with ustekinumab who did not achieve an IGA of 0/1 by week 16 derived significant benefit from switching to guselkumab. What's already known about this topic? Interleukin (IL)‐23/IL‐17 is the major pathway that drives the chronic inflammation underlying the pathophysiology of psoriasis. Ustekinumab is a monoclonal antibody targeting IL‐12 and IL‐23 and is currently approved for patients with plaque psoriasis. Guselkumab is a novel anti‐IL‐23 monoclonal antibody and has demonstrated high efficacy in patients with plaque psoriasis in two recent phase III trials. What does this study add? Guselkumab demonstrated greater efficacy compared with ustekinumab among patients who failed to achieve an Investigator's Global Assessment score of 0 or 1 with ustekinumab therapy. The types of adverse events (AEs) with guselkumab and ustekinumab were similar, with infections being the most common. A slightly higher incidence of AEs was reported in the guselkumab group, primarily driven by AEs of back pain, psoriatic arthropathy and mild injection site reactions. Linked Comment: Albrecht and Gerdes. Br J Dermatol 2018; 178:20. Plain language summary available online</description><identifier>ISSN: 0007-0963</identifier><identifier>EISSN: 1365-2133</identifier><identifier>DOI: 10.1111/bjd.15750</identifier><identifier>PMID: 28635018</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adult ; Antibodies, Monoclonal - administration &amp; dosage ; Antibodies, Monoclonal - adverse effects ; Biological Products - administration &amp; dosage ; Biological Products - adverse effects ; Clinical trials ; Cytokines ; Dermatologic Agents - administration &amp; dosage ; Dermatologic Agents - adverse effects ; Double-Blind Method ; Double-blind studies ; Drug therapy ; Female ; Humans ; Immunoglobulin A ; Immunotherapy ; Interleukin 12 ; Interleukin 17 ; Interleukin 23 ; Male ; Monoclonal antibodies ; Pain ; Patient Reported Outcome Measures ; Psoriasis ; Psoriasis - drug therapy ; Side effects ; Treatment Outcome ; Ustekinumab - administration &amp; dosage ; Ustekinumab - adverse effects</subject><ispartof>British journal of dermatology (1951), 2018-01, Vol.178 (1), p.114-123</ispartof><rights>2017 British Association of Dermatologists</rights><rights>2017 British Association of Dermatologists.</rights><rights>Copyright © 2018 British Association of Dermatologists</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3880-c29dca482c736837ceffa8e217777ba030e6624f3cc0d67e76fd18cc9f865d863</citedby><cites>FETCH-LOGICAL-c3880-c29dca482c736837ceffa8e217777ba030e6624f3cc0d67e76fd18cc9f865d863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbjd.15750$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbjd.15750$$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/28635018$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Langley, R.G.</creatorcontrib><creatorcontrib>Tsai, T.‐F.</creatorcontrib><creatorcontrib>Flavin, S.</creatorcontrib><creatorcontrib>Song, M.</creatorcontrib><creatorcontrib>Randazzo, B.</creatorcontrib><creatorcontrib>Wasfi, Y.</creatorcontrib><creatorcontrib>Jiang, J.</creatorcontrib><creatorcontrib>Li, S.</creatorcontrib><creatorcontrib>Puig, L.</creatorcontrib><title>Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double‐blind, phase III NAVIGATE trial</title><title>British journal of dermatology (1951)</title><addtitle>Br J Dermatol</addtitle><description>Summary Background Guselkumab, an anti‐interleukin‐23 monoclonal antibody, has demonstrated significant efficacy in phase III psoriasis trials. Objectives To evaluate the efficacy and safety of guselkumab in patients with moderate‐to‐severe plaque psoriasis who had an inadequate response to ustekinumab. Methods In this phase III, randomized, double‐blind study, 871 patients received open‐label ustekinumab (45 mg or 90 mg) at weeks 0 and 4. At week 16, 268 patients with an inadequate response to ustekinumab [Investigator's Global Assessment (IGA) ≥ 2] were randomized (double‐blind) to guselkumab 100 mg or to continue ustekinumab; 585 of 871 patients (67%) with IGA 0/1 at week 16 continued open‐label ustekinumab. The primary end point was the number of visits at which randomized patients achieved IGA 0/1 and at least a two‐grade improvement (from week 16) from week 28 to week 40. Improvement ≥ 90% or 100% in Psoriasis Area and Severity Index (PASI 90/100) and Dermatology Life Quality Index (DLQI) of 0/1 were also assessed. Results The mean number of visits at which patients achieved IGA 0/1 and at least a two‐grade improvemen (week 28–40) was significantly greater in the guselkumab group vs. the randomized ustekinumab group (1·5 vs. 0·7; P &lt; 0·001); greater proportions of patients in the guselkumab group achieved IGA 0/1 and at least a two‐grade improvement at week 28 (31·1% vs. 14·3%; P = 0·001) and week 52 (36·3% vs. 17·3%; P &lt; 0·001). Greater proportions of patients treated with guselkumab achieved PASI 90, PASI 100 and DLQI 0/1 at week 52. After week 16, 64·4% of patients in the guselkumab group and 55·6% in the ustekinumab group had at least one adverse event (AE); infections were the most frequent AE type. Overall, 6·7% (n = 9) of patients in the guselkumab group had at least one serious AE compared with 4·5% (n = 6) for the ustekinumab group. Conclusions Patients treated with ustekinumab who did not achieve an IGA of 0/1 by week 16 derived significant benefit from switching to guselkumab. What's already known about this topic? Interleukin (IL)‐23/IL‐17 is the major pathway that drives the chronic inflammation underlying the pathophysiology of psoriasis. Ustekinumab is a monoclonal antibody targeting IL‐12 and IL‐23 and is currently approved for patients with plaque psoriasis. Guselkumab is a novel anti‐IL‐23 monoclonal antibody and has demonstrated high efficacy in patients with plaque psoriasis in two recent phase III trials. What does this study add? Guselkumab demonstrated greater efficacy compared with ustekinumab among patients who failed to achieve an Investigator's Global Assessment score of 0 or 1 with ustekinumab therapy. The types of adverse events (AEs) with guselkumab and ustekinumab were similar, with infections being the most common. A slightly higher incidence of AEs was reported in the guselkumab group, primarily driven by AEs of back pain, psoriatic arthropathy and mild injection site reactions. Linked Comment: Albrecht and Gerdes. Br J Dermatol 2018; 178:20. Plain language summary available online</description><subject>Adult</subject><subject>Antibodies, Monoclonal - administration &amp; dosage</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Biological Products - administration &amp; dosage</subject><subject>Biological Products - adverse effects</subject><subject>Clinical trials</subject><subject>Cytokines</subject><subject>Dermatologic Agents - administration &amp; dosage</subject><subject>Dermatologic Agents - adverse effects</subject><subject>Double-Blind Method</subject><subject>Double-blind studies</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin A</subject><subject>Immunotherapy</subject><subject>Interleukin 12</subject><subject>Interleukin 17</subject><subject>Interleukin 23</subject><subject>Male</subject><subject>Monoclonal antibodies</subject><subject>Pain</subject><subject>Patient Reported Outcome Measures</subject><subject>Psoriasis</subject><subject>Psoriasis - drug therapy</subject><subject>Side effects</subject><subject>Treatment Outcome</subject><subject>Ustekinumab - administration &amp; 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dosage</topic><topic>Ustekinumab - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Langley, R.G.</creatorcontrib><creatorcontrib>Tsai, T.‐F.</creatorcontrib><creatorcontrib>Flavin, S.</creatorcontrib><creatorcontrib>Song, M.</creatorcontrib><creatorcontrib>Randazzo, B.</creatorcontrib><creatorcontrib>Wasfi, Y.</creatorcontrib><creatorcontrib>Jiang, J.</creatorcontrib><creatorcontrib>Li, S.</creatorcontrib><creatorcontrib>Puig, L.</creatorcontrib><collection>Wiley Online Library 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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of dermatology (1951)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Langley, R.G.</au><au>Tsai, T.‐F.</au><au>Flavin, S.</au><au>Song, M.</au><au>Randazzo, B.</au><au>Wasfi, Y.</au><au>Jiang, J.</au><au>Li, S.</au><au>Puig, L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double‐blind, phase III NAVIGATE trial</atitle><jtitle>British journal of dermatology (1951)</jtitle><addtitle>Br J Dermatol</addtitle><date>2018-01</date><risdate>2018</risdate><volume>178</volume><issue>1</issue><spage>114</spage><epage>123</epage><pages>114-123</pages><issn>0007-0963</issn><eissn>1365-2133</eissn><abstract>Summary Background Guselkumab, an anti‐interleukin‐23 monoclonal antibody, has demonstrated significant efficacy in phase III psoriasis trials. Objectives To evaluate the efficacy and safety of guselkumab in patients with moderate‐to‐severe plaque psoriasis who had an inadequate response to ustekinumab. Methods In this phase III, randomized, double‐blind study, 871 patients received open‐label ustekinumab (45 mg or 90 mg) at weeks 0 and 4. At week 16, 268 patients with an inadequate response to ustekinumab [Investigator's Global Assessment (IGA) ≥ 2] were randomized (double‐blind) to guselkumab 100 mg or to continue ustekinumab; 585 of 871 patients (67%) with IGA 0/1 at week 16 continued open‐label ustekinumab. The primary end point was the number of visits at which randomized patients achieved IGA 0/1 and at least a two‐grade improvement (from week 16) from week 28 to week 40. Improvement ≥ 90% or 100% in Psoriasis Area and Severity Index (PASI 90/100) and Dermatology Life Quality Index (DLQI) of 0/1 were also assessed. Results The mean number of visits at which patients achieved IGA 0/1 and at least a two‐grade improvemen (week 28–40) was significantly greater in the guselkumab group vs. the randomized ustekinumab group (1·5 vs. 0·7; P &lt; 0·001); greater proportions of patients in the guselkumab group achieved IGA 0/1 and at least a two‐grade improvement at week 28 (31·1% vs. 14·3%; P = 0·001) and week 52 (36·3% vs. 17·3%; P &lt; 0·001). Greater proportions of patients treated with guselkumab achieved PASI 90, PASI 100 and DLQI 0/1 at week 52. After week 16, 64·4% of patients in the guselkumab group and 55·6% in the ustekinumab group had at least one adverse event (AE); infections were the most frequent AE type. Overall, 6·7% (n = 9) of patients in the guselkumab group had at least one serious AE compared with 4·5% (n = 6) for the ustekinumab group. Conclusions Patients treated with ustekinumab who did not achieve an IGA of 0/1 by week 16 derived significant benefit from switching to guselkumab. What's already known about this topic? Interleukin (IL)‐23/IL‐17 is the major pathway that drives the chronic inflammation underlying the pathophysiology of psoriasis. Ustekinumab is a monoclonal antibody targeting IL‐12 and IL‐23 and is currently approved for patients with plaque psoriasis. Guselkumab is a novel anti‐IL‐23 monoclonal antibody and has demonstrated high efficacy in patients with plaque psoriasis in two recent phase III trials. What does this study add? Guselkumab demonstrated greater efficacy compared with ustekinumab among patients who failed to achieve an Investigator's Global Assessment score of 0 or 1 with ustekinumab therapy. The types of adverse events (AEs) with guselkumab and ustekinumab were similar, with infections being the most common. A slightly higher incidence of AEs was reported in the guselkumab group, primarily driven by AEs of back pain, psoriatic arthropathy and mild injection site reactions. Linked Comment: Albrecht and Gerdes. Br J Dermatol 2018; 178:20. Plain language summary available online</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>28635018</pmid><doi>10.1111/bjd.15750</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Adult
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal - adverse effects
Biological Products - administration & dosage
Biological Products - adverse effects
Clinical trials
Cytokines
Dermatologic Agents - administration & dosage
Dermatologic Agents - adverse effects
Double-Blind Method
Double-blind studies
Drug therapy
Female
Humans
Immunoglobulin A
Immunotherapy
Interleukin 12
Interleukin 17
Interleukin 23
Male
Monoclonal antibodies
Pain
Patient Reported Outcome Measures
Psoriasis
Psoriasis - drug therapy
Side effects
Treatment Outcome
Ustekinumab - administration & dosage
Ustekinumab - adverse effects
title Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double‐blind, phase III NAVIGATE trial
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