Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis: A Randomized Clinical Trial
IMPORTANCE: The dupilumab regimen of 300 mg every 2 weeks is approved for uncontrolled, moderate to severe atopic dermatitis (AD). OBJECTIVE: To assess the efficacy and safety of different dupilumab regimens in maintaining response after 16 weeks of initial treatment. DESIGN, SETTING, AND PARTICIPAN...
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| creator | Worm, Margitta Simpson, Eric L Thaçi, Diamant Bissonnette, Robert Lacour, Jean-Philippe Beissert, Stefan Kawashima, Makoto Ferrándiz, Carlos Smith, Catherine H Beck, Lisa A Chan, Kuo-Chen Chen, Zhen Akinlade, Bolanle Hultsch, Thomas Staudinger, Heribert Gadkari, Abhijit Eckert, Laurent Davis, John D Rajadhyaksha, Manoj Graham, Neil M. H Pirozzi, Gianluca Stahl, Neil Yancopoulos, George D Ardeleanu, Marius |
| description | IMPORTANCE: The dupilumab regimen of 300 mg every 2 weeks is approved for uncontrolled, moderate to severe atopic dermatitis (AD). OBJECTIVE: To assess the efficacy and safety of different dupilumab regimens in maintaining response after 16 weeks of initial treatment. DESIGN, SETTING, AND PARTICIPANTS: The Study to Confirm the Efficacy and Safety of Different Dupilumab Dose Regimens in Adults With Atopic Dermatitis (LIBERTY AD SOLO-CONTINUE) was a randomized, double-blind, phase 3 clinical trial conducted from March 25, 2015, to October 18, 2016, at 185 sites in North America, Europe, Asia, and Japan. Patients with moderate to severe AD who received dupilumab treatment and achieved an Investigator’s Global Assessment score of 0 or 1 or 75% improvement in Eczema Area and Severity Index scores (EASI-75) at week 16 in 2 previous dupilumab monotherapy trials (LIBERTY AD SOLO 1 and 2) were rerandomized in SOLO-CONTINUE. After completing SOLO-CONTINUE, patients were followed up for up to 12 weeks or enrolled in an open-label extension. Data were analyzed from December 5 to 12, 2016. INTERVENTIONS: High-responding patients treated with dupilumab in SOLO were rerandomized 2:1:1:1 to continue their original regimen of dupilumab, 300 mg, weekly or every 2 weeks or to receive dupilumab, 300 mg, every 4 or 8 weeks or placebo for 36 weeks. MAIN OUTCOMES AND MEASURES: Percentage change in EASI score from baseline during the SOLO-CONTINUE trial, percentage of patients with EASI-75 at week 36, and safety. RESULTS: Among the 422 patients (mean [SD] age, 38.2 [14.5] years; 227 [53.8%] male), continuing dupilumab treatment once weekly or every 2 weeks maintained optimal efficacy, with negligible change in percent EASI improvement from SOLO 1 and 2 baseline during the SOLO-CONTINUE trial (−0.06%; P |
| doi_str_mv | 10.1001/jamadermatol.2019.3617 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6990756</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><ama_id>2757721</ama_id><sourcerecordid>2358481000</sourcerecordid><originalsourceid>FETCH-LOGICAL-a360t-92de1d32ecf77f7d2f62096c7f1b8e3c2750aeb41ac3022ae95a3b94b02b5dbf3</originalsourceid><addsrcrecordid>eNpVkV9rFDEUxQdRbKn9Aj6UCz7vmj8zyYwPwrJbtVBR2oqP4U4mabPMTMYkI6wfxU9r1q1LzUsC95xzT_gVxQUlS0oIfbvFATsTBky-XzJCmyUXVD4rThkV9UKQunx-fIv6pDiPcUvyqQkpOX1ZnHBaS9EQclr8vrTWadQ7wLGDW7Qm7cBb-Dz3yU29gc08uX4esIWNjwZuzL0bzBhhZZMJcDW65LCH21lrE6Ode7gLBlOWJHAjfMXk8jPCd5ceYJX85DRs_lbPxvgOVnCTF_vB_TIdrHs35jL7jBz6qnhhsY_m_PE-K759uLxbf1pcf_l4tV5dL5ALkhYN6wztODPaSmllx6xgpBFaWtrWhmsmK4KmLSlqThhD01TI26ZsCWurrrX8rHh_yJ3mdjCdzn0D9moKbsCwUx6d-n8yugd1738q0TREViIHvHkMCP7HbGJSWz-HMXdWjFd1WWdoJKvEQaWDjzEYe9xAidpjVU-xqj1WtceajRdP-x1t_yBmweuDIPuP0_xtKRnlfwAIfa3x</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2358481000</pqid></control><display><type>article</type><title>Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis: A Randomized Clinical Trial</title><source>MEDLINE</source><source>American Medical Association Journals (including JAMA)</source><creator>Worm, Margitta ; Simpson, Eric L ; Thaçi, Diamant ; Bissonnette, Robert ; Lacour, Jean-Philippe ; Beissert, Stefan ; Kawashima, Makoto ; Ferrándiz, Carlos ; Smith, Catherine H ; Beck, Lisa A ; Chan, Kuo-Chen ; Chen, Zhen ; Akinlade, Bolanle ; Hultsch, Thomas ; Staudinger, Heribert ; Gadkari, Abhijit ; Eckert, Laurent ; Davis, John D ; Rajadhyaksha, Manoj ; Graham, Neil M. H ; Pirozzi, Gianluca ; Stahl, Neil ; Yancopoulos, George D ; Ardeleanu, Marius</creator><creatorcontrib>Worm, Margitta ; Simpson, Eric L ; Thaçi, Diamant ; Bissonnette, Robert ; Lacour, Jean-Philippe ; Beissert, Stefan ; Kawashima, Makoto ; Ferrándiz, Carlos ; Smith, Catherine H ; Beck, Lisa A ; Chan, Kuo-Chen ; Chen, Zhen ; Akinlade, Bolanle ; Hultsch, Thomas ; Staudinger, Heribert ; Gadkari, Abhijit ; Eckert, Laurent ; Davis, John D ; Rajadhyaksha, Manoj ; Graham, Neil M. H ; Pirozzi, Gianluca ; Stahl, Neil ; Yancopoulos, George D ; Ardeleanu, Marius</creatorcontrib><description>IMPORTANCE: The dupilumab regimen of 300 mg every 2 weeks is approved for uncontrolled, moderate to severe atopic dermatitis (AD). OBJECTIVE: To assess the efficacy and safety of different dupilumab regimens in maintaining response after 16 weeks of initial treatment. DESIGN, SETTING, AND PARTICIPANTS: The Study to Confirm the Efficacy and Safety of Different Dupilumab Dose Regimens in Adults With Atopic Dermatitis (LIBERTY AD SOLO-CONTINUE) was a randomized, double-blind, phase 3 clinical trial conducted from March 25, 2015, to October 18, 2016, at 185 sites in North America, Europe, Asia, and Japan. Patients with moderate to severe AD who received dupilumab treatment and achieved an Investigator’s Global Assessment score of 0 or 1 or 75% improvement in Eczema Area and Severity Index scores (EASI-75) at week 16 in 2 previous dupilumab monotherapy trials (LIBERTY AD SOLO 1 and 2) were rerandomized in SOLO-CONTINUE. After completing SOLO-CONTINUE, patients were followed up for up to 12 weeks or enrolled in an open-label extension. Data were analyzed from December 5 to 12, 2016. INTERVENTIONS: High-responding patients treated with dupilumab in SOLO were rerandomized 2:1:1:1 to continue their original regimen of dupilumab, 300 mg, weekly or every 2 weeks or to receive dupilumab, 300 mg, every 4 or 8 weeks or placebo for 36 weeks. MAIN OUTCOMES AND MEASURES: Percentage change in EASI score from baseline during the SOLO-CONTINUE trial, percentage of patients with EASI-75 at week 36, and safety. RESULTS: Among the 422 patients (mean [SD] age, 38.2 [14.5] years; 227 [53.8%] male), continuing dupilumab treatment once weekly or every 2 weeks maintained optimal efficacy, with negligible change in percent EASI improvement from SOLO 1 and 2 baseline during the SOLO-CONTINUE trial (−0.06%; P < .001 vs placebo); percent change with the other regimens dose-dependently worsened (dupilumab every 4 weeks, −3.84%; dupilumab every 8 weeks, −6.84%; placebo, −21.67%). More patients taking dupilumab weekly or every 2 weeks (116 of 162 [71.6%]; P < .001 vs placebo) maintained EASI-75 response than those taking dupilumab every 4 weeks (49 of 84 [58.3%]) or every 8 weeks (45 of 82 [54.9%]) or those taking placebo (24 of 79 [30.4%]). Overall adverse event incidences were 70.7% in the weekly or every 2 weeks group, 73.6% in the every 4 weeks group, 75.0% in the every 8 weeks group, and 81.7% in the placebo group. Treatment groups had similar conjunctivitis rates. Treatment-emergent antidrug antibody incidence was lower with more frequent dupilumab dose regimens (11.3% in the placebo group and 11.7%, 6.0%, 4.3%, and 1.2% in the dupilumab every 8 weeks, every 4 weeks, every 2 weeks, and weekly groups, respectively). CONCLUSIONS AND RELEVANCE: In this trial, continued response over time was most consistently maintained with dupilumab administered weekly or every 2 weeks. Longer dosage intervals and placebo resulted in a diminution of response for both continuous and categorical end points. No new safety signals were observed. The approved regimen of 300 mg of dupilumab every 2 weeks is recommended for long-term treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02395133</description><identifier>ISSN: 2168-6068</identifier><identifier>EISSN: 2168-6084</identifier><identifier>DOI: 10.1001/jamadermatol.2019.3617</identifier><identifier>PMID: 31876900</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Adult ; Antibodies, Monoclonal, Humanized - administration & dosage ; Antibodies, Monoclonal, Humanized - adverse effects ; Clinical outcomes ; Clinical trials ; Comments ; Dermatitis ; Dermatitis, Atopic - drug therapy ; Dermatitis, Atopic - pathology ; Dermatologic Agents - administration & dosage ; Dermatologic Agents - adverse effects ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug therapy ; Eczema ; Female ; Humans ; Immunotherapy ; Male ; Middle Aged ; Monoclonal antibodies ; Online First ; Original Investigation ; Severity of Illness Index ; Treatment Outcome ; Young Adult</subject><ispartof>Archives of dermatology (1960), 2020-02, Vol.156 (2), p.131-143</ispartof><rights>Copyright American Medical Association Feb 2020</rights><rights>Copyright 2019 Worm M et al. .</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a360t-92de1d32ecf77f7d2f62096c7f1b8e3c2750aeb41ac3022ae95a3b94b02b5dbf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jamadermatology/articlepdf/10.1001/jamadermatol.2019.3617$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jamadermatology/fullarticle/10.1001/jamadermatol.2019.3617$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,230,314,780,784,885,3331,27915,27916,76250,76253</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31876900$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Worm, Margitta</creatorcontrib><creatorcontrib>Simpson, Eric L</creatorcontrib><creatorcontrib>Thaçi, Diamant</creatorcontrib><creatorcontrib>Bissonnette, Robert</creatorcontrib><creatorcontrib>Lacour, Jean-Philippe</creatorcontrib><creatorcontrib>Beissert, Stefan</creatorcontrib><creatorcontrib>Kawashima, Makoto</creatorcontrib><creatorcontrib>Ferrándiz, Carlos</creatorcontrib><creatorcontrib>Smith, Catherine H</creatorcontrib><creatorcontrib>Beck, Lisa A</creatorcontrib><creatorcontrib>Chan, Kuo-Chen</creatorcontrib><creatorcontrib>Chen, Zhen</creatorcontrib><creatorcontrib>Akinlade, Bolanle</creatorcontrib><creatorcontrib>Hultsch, Thomas</creatorcontrib><creatorcontrib>Staudinger, Heribert</creatorcontrib><creatorcontrib>Gadkari, Abhijit</creatorcontrib><creatorcontrib>Eckert, Laurent</creatorcontrib><creatorcontrib>Davis, John D</creatorcontrib><creatorcontrib>Rajadhyaksha, Manoj</creatorcontrib><creatorcontrib>Graham, Neil M. H</creatorcontrib><creatorcontrib>Pirozzi, Gianluca</creatorcontrib><creatorcontrib>Stahl, Neil</creatorcontrib><creatorcontrib>Yancopoulos, George D</creatorcontrib><creatorcontrib>Ardeleanu, Marius</creatorcontrib><title>Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis: A Randomized Clinical Trial</title><title>Archives of dermatology (1960)</title><addtitle>JAMA Dermatol</addtitle><description>IMPORTANCE: The dupilumab regimen of 300 mg every 2 weeks is approved for uncontrolled, moderate to severe atopic dermatitis (AD). OBJECTIVE: To assess the efficacy and safety of different dupilumab regimens in maintaining response after 16 weeks of initial treatment. DESIGN, SETTING, AND PARTICIPANTS: The Study to Confirm the Efficacy and Safety of Different Dupilumab Dose Regimens in Adults With Atopic Dermatitis (LIBERTY AD SOLO-CONTINUE) was a randomized, double-blind, phase 3 clinical trial conducted from March 25, 2015, to October 18, 2016, at 185 sites in North America, Europe, Asia, and Japan. Patients with moderate to severe AD who received dupilumab treatment and achieved an Investigator’s Global Assessment score of 0 or 1 or 75% improvement in Eczema Area and Severity Index scores (EASI-75) at week 16 in 2 previous dupilumab monotherapy trials (LIBERTY AD SOLO 1 and 2) were rerandomized in SOLO-CONTINUE. After completing SOLO-CONTINUE, patients were followed up for up to 12 weeks or enrolled in an open-label extension. Data were analyzed from December 5 to 12, 2016. INTERVENTIONS: High-responding patients treated with dupilumab in SOLO were rerandomized 2:1:1:1 to continue their original regimen of dupilumab, 300 mg, weekly or every 2 weeks or to receive dupilumab, 300 mg, every 4 or 8 weeks or placebo for 36 weeks. MAIN OUTCOMES AND MEASURES: Percentage change in EASI score from baseline during the SOLO-CONTINUE trial, percentage of patients with EASI-75 at week 36, and safety. RESULTS: Among the 422 patients (mean [SD] age, 38.2 [14.5] years; 227 [53.8%] male), continuing dupilumab treatment once weekly or every 2 weeks maintained optimal efficacy, with negligible change in percent EASI improvement from SOLO 1 and 2 baseline during the SOLO-CONTINUE trial (−0.06%; P < .001 vs placebo); percent change with the other regimens dose-dependently worsened (dupilumab every 4 weeks, −3.84%; dupilumab every 8 weeks, −6.84%; placebo, −21.67%). More patients taking dupilumab weekly or every 2 weeks (116 of 162 [71.6%]; P < .001 vs placebo) maintained EASI-75 response than those taking dupilumab every 4 weeks (49 of 84 [58.3%]) or every 8 weeks (45 of 82 [54.9%]) or those taking placebo (24 of 79 [30.4%]). Overall adverse event incidences were 70.7% in the weekly or every 2 weeks group, 73.6% in the every 4 weeks group, 75.0% in the every 8 weeks group, and 81.7% in the placebo group. Treatment groups had similar conjunctivitis rates. Treatment-emergent antidrug antibody incidence was lower with more frequent dupilumab dose regimens (11.3% in the placebo group and 11.7%, 6.0%, 4.3%, and 1.2% in the dupilumab every 8 weeks, every 4 weeks, every 2 weeks, and weekly groups, respectively). CONCLUSIONS AND RELEVANCE: In this trial, continued response over time was most consistently maintained with dupilumab administered weekly or every 2 weeks. Longer dosage intervals and placebo resulted in a diminution of response for both continuous and categorical end points. No new safety signals were observed. The approved regimen of 300 mg of dupilumab every 2 weeks is recommended for long-term treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02395133</description><subject>Adult</subject><subject>Antibodies, Monoclonal, Humanized - administration & dosage</subject><subject>Antibodies, Monoclonal, Humanized - adverse effects</subject><subject>Clinical outcomes</subject><subject>Clinical trials</subject><subject>Comments</subject><subject>Dermatitis</subject><subject>Dermatitis, Atopic - drug therapy</subject><subject>Dermatitis, Atopic - pathology</subject><subject>Dermatologic Agents - administration & dosage</subject><subject>Dermatologic Agents - adverse effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Drug therapy</subject><subject>Eczema</subject><subject>Female</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Online First</subject><subject>Original Investigation</subject><subject>Severity of Illness Index</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>2168-6068</issn><issn>2168-6084</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkV9rFDEUxQdRbKn9Aj6UCz7vmj8zyYwPwrJbtVBR2oqP4U4mabPMTMYkI6wfxU9r1q1LzUsC95xzT_gVxQUlS0oIfbvFATsTBky-XzJCmyUXVD4rThkV9UKQunx-fIv6pDiPcUvyqQkpOX1ZnHBaS9EQclr8vrTWadQ7wLGDW7Qm7cBb-Dz3yU29gc08uX4esIWNjwZuzL0bzBhhZZMJcDW65LCH21lrE6Ode7gLBlOWJHAjfMXk8jPCd5ceYJX85DRs_lbPxvgOVnCTF_vB_TIdrHs35jL7jBz6qnhhsY_m_PE-K759uLxbf1pcf_l4tV5dL5ALkhYN6wztODPaSmllx6xgpBFaWtrWhmsmK4KmLSlqThhD01TI26ZsCWurrrX8rHh_yJ3mdjCdzn0D9moKbsCwUx6d-n8yugd1738q0TREViIHvHkMCP7HbGJSWz-HMXdWjFd1WWdoJKvEQaWDjzEYe9xAidpjVU-xqj1WtceajRdP-x1t_yBmweuDIPuP0_xtKRnlfwAIfa3x</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>Worm, Margitta</creator><creator>Simpson, Eric L</creator><creator>Thaçi, Diamant</creator><creator>Bissonnette, Robert</creator><creator>Lacour, Jean-Philippe</creator><creator>Beissert, Stefan</creator><creator>Kawashima, Makoto</creator><creator>Ferrándiz, Carlos</creator><creator>Smith, Catherine H</creator><creator>Beck, Lisa A</creator><creator>Chan, Kuo-Chen</creator><creator>Chen, Zhen</creator><creator>Akinlade, Bolanle</creator><creator>Hultsch, Thomas</creator><creator>Staudinger, Heribert</creator><creator>Gadkari, Abhijit</creator><creator>Eckert, Laurent</creator><creator>Davis, John D</creator><creator>Rajadhyaksha, Manoj</creator><creator>Graham, Neil M. H</creator><creator>Pirozzi, Gianluca</creator><creator>Stahl, Neil</creator><creator>Yancopoulos, George D</creator><creator>Ardeleanu, Marius</creator><general>American Medical Association</general><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>K9.</scope><scope>NAPCQ</scope><scope>5PM</scope></search><sort><creationdate>20200201</creationdate><title>Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis: A Randomized Clinical Trial</title><author>Worm, Margitta ; Simpson, Eric L ; Thaçi, Diamant ; Bissonnette, Robert ; Lacour, Jean-Philippe ; Beissert, Stefan ; Kawashima, Makoto ; Ferrándiz, Carlos ; Smith, Catherine H ; Beck, Lisa A ; Chan, Kuo-Chen ; Chen, Zhen ; Akinlade, Bolanle ; Hultsch, Thomas ; Staudinger, Heribert ; Gadkari, Abhijit ; Eckert, Laurent ; Davis, John D ; Rajadhyaksha, Manoj ; Graham, Neil M. H ; Pirozzi, Gianluca ; Stahl, Neil ; Yancopoulos, George D ; Ardeleanu, Marius</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a360t-92de1d32ecf77f7d2f62096c7f1b8e3c2750aeb41ac3022ae95a3b94b02b5dbf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Antibodies, Monoclonal, Humanized - administration & dosage</topic><topic>Antibodies, Monoclonal, Humanized - adverse effects</topic><topic>Clinical outcomes</topic><topic>Clinical trials</topic><topic>Comments</topic><topic>Dermatitis</topic><topic>Dermatitis, Atopic - drug therapy</topic><topic>Dermatitis, Atopic - pathology</topic><topic>Dermatologic Agents - administration & dosage</topic><topic>Dermatologic Agents - adverse effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Double-Blind Method</topic><topic>Drug therapy</topic><topic>Eczema</topic><topic>Female</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Online First</topic><topic>Original Investigation</topic><topic>Severity of Illness Index</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Worm, Margitta</creatorcontrib><creatorcontrib>Simpson, Eric L</creatorcontrib><creatorcontrib>Thaçi, Diamant</creatorcontrib><creatorcontrib>Bissonnette, Robert</creatorcontrib><creatorcontrib>Lacour, Jean-Philippe</creatorcontrib><creatorcontrib>Beissert, Stefan</creatorcontrib><creatorcontrib>Kawashima, Makoto</creatorcontrib><creatorcontrib>Ferrándiz, Carlos</creatorcontrib><creatorcontrib>Smith, Catherine H</creatorcontrib><creatorcontrib>Beck, Lisa A</creatorcontrib><creatorcontrib>Chan, Kuo-Chen</creatorcontrib><creatorcontrib>Chen, Zhen</creatorcontrib><creatorcontrib>Akinlade, Bolanle</creatorcontrib><creatorcontrib>Hultsch, Thomas</creatorcontrib><creatorcontrib>Staudinger, Heribert</creatorcontrib><creatorcontrib>Gadkari, Abhijit</creatorcontrib><creatorcontrib>Eckert, Laurent</creatorcontrib><creatorcontrib>Davis, John D</creatorcontrib><creatorcontrib>Rajadhyaksha, Manoj</creatorcontrib><creatorcontrib>Graham, Neil M. H</creatorcontrib><creatorcontrib>Pirozzi, Gianluca</creatorcontrib><creatorcontrib>Stahl, Neil</creatorcontrib><creatorcontrib>Yancopoulos, George D</creatorcontrib><creatorcontrib>Ardeleanu, Marius</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Archives of dermatology (1960)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Worm, Margitta</au><au>Simpson, Eric L</au><au>Thaçi, Diamant</au><au>Bissonnette, Robert</au><au>Lacour, Jean-Philippe</au><au>Beissert, Stefan</au><au>Kawashima, Makoto</au><au>Ferrándiz, Carlos</au><au>Smith, Catherine H</au><au>Beck, Lisa A</au><au>Chan, Kuo-Chen</au><au>Chen, Zhen</au><au>Akinlade, Bolanle</au><au>Hultsch, Thomas</au><au>Staudinger, Heribert</au><au>Gadkari, Abhijit</au><au>Eckert, Laurent</au><au>Davis, John D</au><au>Rajadhyaksha, Manoj</au><au>Graham, Neil M. H</au><au>Pirozzi, Gianluca</au><au>Stahl, Neil</au><au>Yancopoulos, George D</au><au>Ardeleanu, Marius</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis: A Randomized Clinical Trial</atitle><jtitle>Archives of dermatology (1960)</jtitle><addtitle>JAMA Dermatol</addtitle><date>2020-02-01</date><risdate>2020</risdate><volume>156</volume><issue>2</issue><spage>131</spage><epage>143</epage><pages>131-143</pages><issn>2168-6068</issn><eissn>2168-6084</eissn><abstract>IMPORTANCE: The dupilumab regimen of 300 mg every 2 weeks is approved for uncontrolled, moderate to severe atopic dermatitis (AD). OBJECTIVE: To assess the efficacy and safety of different dupilumab regimens in maintaining response after 16 weeks of initial treatment. DESIGN, SETTING, AND PARTICIPANTS: The Study to Confirm the Efficacy and Safety of Different Dupilumab Dose Regimens in Adults With Atopic Dermatitis (LIBERTY AD SOLO-CONTINUE) was a randomized, double-blind, phase 3 clinical trial conducted from March 25, 2015, to October 18, 2016, at 185 sites in North America, Europe, Asia, and Japan. Patients with moderate to severe AD who received dupilumab treatment and achieved an Investigator’s Global Assessment score of 0 or 1 or 75% improvement in Eczema Area and Severity Index scores (EASI-75) at week 16 in 2 previous dupilumab monotherapy trials (LIBERTY AD SOLO 1 and 2) were rerandomized in SOLO-CONTINUE. After completing SOLO-CONTINUE, patients were followed up for up to 12 weeks or enrolled in an open-label extension. Data were analyzed from December 5 to 12, 2016. INTERVENTIONS: High-responding patients treated with dupilumab in SOLO were rerandomized 2:1:1:1 to continue their original regimen of dupilumab, 300 mg, weekly or every 2 weeks or to receive dupilumab, 300 mg, every 4 or 8 weeks or placebo for 36 weeks. MAIN OUTCOMES AND MEASURES: Percentage change in EASI score from baseline during the SOLO-CONTINUE trial, percentage of patients with EASI-75 at week 36, and safety. RESULTS: Among the 422 patients (mean [SD] age, 38.2 [14.5] years; 227 [53.8%] male), continuing dupilumab treatment once weekly or every 2 weeks maintained optimal efficacy, with negligible change in percent EASI improvement from SOLO 1 and 2 baseline during the SOLO-CONTINUE trial (−0.06%; P < .001 vs placebo); percent change with the other regimens dose-dependently worsened (dupilumab every 4 weeks, −3.84%; dupilumab every 8 weeks, −6.84%; placebo, −21.67%). More patients taking dupilumab weekly or every 2 weeks (116 of 162 [71.6%]; P < .001 vs placebo) maintained EASI-75 response than those taking dupilumab every 4 weeks (49 of 84 [58.3%]) or every 8 weeks (45 of 82 [54.9%]) or those taking placebo (24 of 79 [30.4%]). Overall adverse event incidences were 70.7% in the weekly or every 2 weeks group, 73.6% in the every 4 weeks group, 75.0% in the every 8 weeks group, and 81.7% in the placebo group. Treatment groups had similar conjunctivitis rates. Treatment-emergent antidrug antibody incidence was lower with more frequent dupilumab dose regimens (11.3% in the placebo group and 11.7%, 6.0%, 4.3%, and 1.2% in the dupilumab every 8 weeks, every 4 weeks, every 2 weeks, and weekly groups, respectively). CONCLUSIONS AND RELEVANCE: In this trial, continued response over time was most consistently maintained with dupilumab administered weekly or every 2 weeks. Longer dosage intervals and placebo resulted in a diminution of response for both continuous and categorical end points. No new safety signals were observed. The approved regimen of 300 mg of dupilumab every 2 weeks is recommended for long-term treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02395133</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>31876900</pmid><doi>10.1001/jamadermatol.2019.3617</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2168-6068 |
| ispartof | Archives of dermatology (1960), 2020-02, Vol.156 (2), p.131-143 |
| issn | 2168-6068 2168-6084 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6990756 |
| source | MEDLINE; American Medical Association Journals (including JAMA) |
| subjects | Adult Antibodies, Monoclonal, Humanized - administration & dosage Antibodies, Monoclonal, Humanized - adverse effects Clinical outcomes Clinical trials Comments Dermatitis Dermatitis, Atopic - drug therapy Dermatitis, Atopic - pathology Dermatologic Agents - administration & dosage Dermatologic Agents - adverse effects Dose-Response Relationship, Drug Double-Blind Method Drug therapy Eczema Female Humans Immunotherapy Male Middle Aged Monoclonal antibodies Online First Original Investigation Severity of Illness Index Treatment Outcome Young Adult |
| title | Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis: A Randomized Clinical Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T19%3A20%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Efficacy%20and%20Safety%20of%20Multiple%20Dupilumab%20Dose%20Regimens%20After%20Initial%20Successful%20Treatment%20in%20Patients%20With%20Atopic%20Dermatitis:%20A%20Randomized%20Clinical%20Trial&rft.jtitle=Archives%20of%20dermatology%20(1960)&rft.au=Worm,%20Margitta&rft.date=2020-02-01&rft.volume=156&rft.issue=2&rft.spage=131&rft.epage=143&rft.pages=131-143&rft.issn=2168-6068&rft.eissn=2168-6084&rft_id=info:doi/10.1001/jamadermatol.2019.3617&rft_dat=%3Cproquest_pubme%3E2358481000%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2358481000&rft_id=info:pmid/31876900&rft_ama_id=2757721&rfr_iscdi=true |