Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials
IMPORTANCE: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. OBJECTIVE: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy f...
Gespeichert in:
| Veröffentlicht in: | JAMA : the journal of the American Medical Association 2024-09, Vol.332 (11), p.881-897 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 897 |
|---|---|
| container_issue | 11 |
| container_start_page | 881 |
| container_title | JAMA : the journal of the American Medical Association |
| container_volume | 332 |
| creator | Louis, Edouard Schreiber, Stefan Panaccione, Remo Bossuyt, Peter Biedermann, Luc Colombel, Jean-Frederic Parkes, Gareth Peyrin-Biroulet, Laurent D’Haens, Geert Hisamatsu, Tadakazu Siegmund, Britta Wu, Kaichun Boland, Brigid S Melmed, Gil Y Armuzzi, Alessandro Levine, Phillip Kalabic, Jasmina Chen, Su Cheng, Ling Shu, Lei Duan, W. Rachel Pivorunas, Valerie Sanchez Gonzalez, Yuri D’Cunha, Ronilda Neimark, Ezequiel Wallace, Kori Atreya, Raja Ferrante, Marc Loftus, Edward V |
| description | IMPORTANCE: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. OBJECTIVE: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. DESIGN, SETTING, AND PARTICIPANTS: Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. INTERVENTIONS: For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. RESULTS: Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P |
| doi_str_mv | 10.1001/jama.2024.12414 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11264075</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><ama_id>2821291</ama_id><sourcerecordid>3112578317</sourcerecordid><originalsourceid>FETCH-LOGICAL-a284t-8036061641c1fab16be8bd170bfd0dddf728d6ed1a9cfcd2b9abb71d97ea220c3</originalsourceid><addsrcrecordid>eNpdkU1r3DAQhkVpaDYf50IPwdBLLt7MSF5L7qUU07SBQCBszkJfbrWxrVSyU5pfX202CW3mMod55mWGh5D3CEsEwLONGtSSAq2WSCus3pAFrpgo2aoRb8kCoBElr0S1Tw5S2kAuZPwd2WcNMC4AFqS99kmNt_5hHpQuuhCLm964qCZ_74o29H7y6VOx_h2KazXaMPgHZ4u296M3qi_W0as-HZG9Ljd3_NQPyc3513X7vby8-nbRfrksFRXVVApgNdRYV2iwUxpr7YS2yEF3Fqy1HafC1s6iakxnLNWN0pqjbbhTlIJhh-TzLvdu1oOzxo1TVL28i35Q8Y8Mysv_J6P_KX-Ee4lI6wr4KiecPiXE8Gt2aZKDT8b1vRpdmJNkIFjNgVPM6MdX6CbMccz_SZbzVlww5Jk621EmhpSi616uQZBbQ3JrSG4NyUdDeePk3yde-GclGfiwA7aLz1MqKNIG2V-cyZXl</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3112578317</pqid></control><display><type>article</type><title>Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials</title><source>MEDLINE</source><source>American Medical Association Journals (including JAMA)</source><creator>Louis, Edouard ; Schreiber, Stefan ; Panaccione, Remo ; Bossuyt, Peter ; Biedermann, Luc ; Colombel, Jean-Frederic ; Parkes, Gareth ; Peyrin-Biroulet, Laurent ; D’Haens, Geert ; Hisamatsu, Tadakazu ; Siegmund, Britta ; Wu, Kaichun ; Boland, Brigid S ; Melmed, Gil Y ; Armuzzi, Alessandro ; Levine, Phillip ; Kalabic, Jasmina ; Chen, Su ; Cheng, Ling ; Shu, Lei ; Duan, W. Rachel ; Pivorunas, Valerie ; Sanchez Gonzalez, Yuri ; D’Cunha, Ronilda ; Neimark, Ezequiel ; Wallace, Kori ; Atreya, Raja ; Ferrante, Marc ; Loftus, Edward V</creator><creatorcontrib>Louis, Edouard ; Schreiber, Stefan ; Panaccione, Remo ; Bossuyt, Peter ; Biedermann, Luc ; Colombel, Jean-Frederic ; Parkes, Gareth ; Peyrin-Biroulet, Laurent ; D’Haens, Geert ; Hisamatsu, Tadakazu ; Siegmund, Britta ; Wu, Kaichun ; Boland, Brigid S ; Melmed, Gil Y ; Armuzzi, Alessandro ; Levine, Phillip ; Kalabic, Jasmina ; Chen, Su ; Cheng, Ling ; Shu, Lei ; Duan, W. Rachel ; Pivorunas, Valerie ; Sanchez Gonzalez, Yuri ; D’Cunha, Ronilda ; Neimark, Ezequiel ; Wallace, Kori ; Atreya, Raja ; Ferrante, Marc ; Loftus, Edward V ; INSPIRE and COMMAND Study Group</creatorcontrib><description>IMPORTANCE: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. OBJECTIVE: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. DESIGN, SETTING, AND PARTICIPANTS: Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. INTERVENTIONS: For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. RESULTS: Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. CONCLUSION AND RELEVANCE: Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135</description><identifier>ISSN: 0098-7484</identifier><identifier>ISSN: 1538-3598</identifier><identifier>EISSN: 1538-3598</identifier><identifier>DOI: 10.1001/jama.2024.12414</identifier><identifier>PMID: 39037800</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Adult ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - adverse effects ; Clinical trials ; Colitis, Ulcerative - diagnosis ; Colitis, Ulcerative - drug therapy ; Colon - diagnostic imaging ; Colon - drug effects ; Colonoscopy ; Double-Blind Method ; Female ; Friability ; Humans ; Induction Chemotherapy - adverse effects ; Induction Chemotherapy - methods ; Inflammatory bowel disease ; Interleukin-23 Subunit p19 - antagonists & inhibitors ; Intestinal Mucosa - diagnostic imaging ; Intestinal Mucosa - drug effects ; Maintenance ; Maintenance Chemotherapy - adverse effects ; Maintenance Chemotherapy - methods ; Male ; Males ; Middle Aged ; Monoclonal antibodies ; Online First ; Original Investigation ; Patients ; Placebos ; Remission ; Remission (Medicine) ; Severity of Illness Index ; Ulcerative colitis</subject><ispartof>JAMA : the journal of the American Medical Association, 2024-09, Vol.332 (11), p.881-897</ispartof><rights>Copyright American Medical Association Sep 17, 2024</rights><rights>Copyright 2024 American Medical Association. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a284t-8036061641c1fab16be8bd170bfd0dddf728d6ed1a9cfcd2b9abb71d97ea220c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jama/articlepdf/10.1001/jama.2024.12414$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2024.12414$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,230,314,776,780,881,3327,27901,27902,76231,76234</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39037800$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Louis, Edouard</creatorcontrib><creatorcontrib>Schreiber, Stefan</creatorcontrib><creatorcontrib>Panaccione, Remo</creatorcontrib><creatorcontrib>Bossuyt, Peter</creatorcontrib><creatorcontrib>Biedermann, Luc</creatorcontrib><creatorcontrib>Colombel, Jean-Frederic</creatorcontrib><creatorcontrib>Parkes, Gareth</creatorcontrib><creatorcontrib>Peyrin-Biroulet, Laurent</creatorcontrib><creatorcontrib>D’Haens, Geert</creatorcontrib><creatorcontrib>Hisamatsu, Tadakazu</creatorcontrib><creatorcontrib>Siegmund, Britta</creatorcontrib><creatorcontrib>Wu, Kaichun</creatorcontrib><creatorcontrib>Boland, Brigid S</creatorcontrib><creatorcontrib>Melmed, Gil Y</creatorcontrib><creatorcontrib>Armuzzi, Alessandro</creatorcontrib><creatorcontrib>Levine, Phillip</creatorcontrib><creatorcontrib>Kalabic, Jasmina</creatorcontrib><creatorcontrib>Chen, Su</creatorcontrib><creatorcontrib>Cheng, Ling</creatorcontrib><creatorcontrib>Shu, Lei</creatorcontrib><creatorcontrib>Duan, W. Rachel</creatorcontrib><creatorcontrib>Pivorunas, Valerie</creatorcontrib><creatorcontrib>Sanchez Gonzalez, Yuri</creatorcontrib><creatorcontrib>D’Cunha, Ronilda</creatorcontrib><creatorcontrib>Neimark, Ezequiel</creatorcontrib><creatorcontrib>Wallace, Kori</creatorcontrib><creatorcontrib>Atreya, Raja</creatorcontrib><creatorcontrib>Ferrante, Marc</creatorcontrib><creatorcontrib>Loftus, Edward V</creatorcontrib><creatorcontrib>INSPIRE and COMMAND Study Group</creatorcontrib><title>Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials</title><title>JAMA : the journal of the American Medical Association</title><addtitle>JAMA</addtitle><description>IMPORTANCE: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. OBJECTIVE: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. DESIGN, SETTING, AND PARTICIPANTS: Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. INTERVENTIONS: For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. RESULTS: Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. CONCLUSION AND RELEVANCE: Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135</description><subject>Adult</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Clinical trials</subject><subject>Colitis, Ulcerative - diagnosis</subject><subject>Colitis, Ulcerative - drug therapy</subject><subject>Colon - diagnostic imaging</subject><subject>Colon - drug effects</subject><subject>Colonoscopy</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Friability</subject><subject>Humans</subject><subject>Induction Chemotherapy - adverse effects</subject><subject>Induction Chemotherapy - methods</subject><subject>Inflammatory bowel disease</subject><subject>Interleukin-23 Subunit p19 - antagonists & inhibitors</subject><subject>Intestinal Mucosa - diagnostic imaging</subject><subject>Intestinal Mucosa - drug effects</subject><subject>Maintenance</subject><subject>Maintenance Chemotherapy - adverse effects</subject><subject>Maintenance Chemotherapy - methods</subject><subject>Male</subject><subject>Males</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Online First</subject><subject>Original Investigation</subject><subject>Patients</subject><subject>Placebos</subject><subject>Remission</subject><subject>Remission (Medicine)</subject><subject>Severity of Illness Index</subject><subject>Ulcerative colitis</subject><issn>0098-7484</issn><issn>1538-3598</issn><issn>1538-3598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1r3DAQhkVpaDYf50IPwdBLLt7MSF5L7qUU07SBQCBszkJfbrWxrVSyU5pfX202CW3mMod55mWGh5D3CEsEwLONGtSSAq2WSCus3pAFrpgo2aoRb8kCoBElr0S1Tw5S2kAuZPwd2WcNMC4AFqS99kmNt_5hHpQuuhCLm964qCZ_74o29H7y6VOx_h2KazXaMPgHZ4u296M3qi_W0as-HZG9Ljd3_NQPyc3513X7vby8-nbRfrksFRXVVApgNdRYV2iwUxpr7YS2yEF3Fqy1HafC1s6iakxnLNWN0pqjbbhTlIJhh-TzLvdu1oOzxo1TVL28i35Q8Y8Mysv_J6P_KX-Ee4lI6wr4KiecPiXE8Gt2aZKDT8b1vRpdmJNkIFjNgVPM6MdX6CbMccz_SZbzVlww5Jk621EmhpSi616uQZBbQ3JrSG4NyUdDeePk3yde-GclGfiwA7aLz1MqKNIG2V-cyZXl</recordid><startdate>20240917</startdate><enddate>20240917</enddate><creator>Louis, Edouard</creator><creator>Schreiber, Stefan</creator><creator>Panaccione, Remo</creator><creator>Bossuyt, Peter</creator><creator>Biedermann, Luc</creator><creator>Colombel, Jean-Frederic</creator><creator>Parkes, Gareth</creator><creator>Peyrin-Biroulet, Laurent</creator><creator>D’Haens, Geert</creator><creator>Hisamatsu, Tadakazu</creator><creator>Siegmund, Britta</creator><creator>Wu, Kaichun</creator><creator>Boland, Brigid S</creator><creator>Melmed, Gil Y</creator><creator>Armuzzi, Alessandro</creator><creator>Levine, Phillip</creator><creator>Kalabic, Jasmina</creator><creator>Chen, Su</creator><creator>Cheng, Ling</creator><creator>Shu, Lei</creator><creator>Duan, W. Rachel</creator><creator>Pivorunas, Valerie</creator><creator>Sanchez Gonzalez, Yuri</creator><creator>D’Cunha, Ronilda</creator><creator>Neimark, Ezequiel</creator><creator>Wallace, Kori</creator><creator>Atreya, Raja</creator><creator>Ferrante, Marc</creator><creator>Loftus, Edward V</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>7QL</scope><scope>7QP</scope><scope>7TK</scope><scope>7TS</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20240917</creationdate><title>Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials</title><author>Louis, Edouard ; Schreiber, Stefan ; Panaccione, Remo ; Bossuyt, Peter ; Biedermann, Luc ; Colombel, Jean-Frederic ; Parkes, Gareth ; Peyrin-Biroulet, Laurent ; D’Haens, Geert ; Hisamatsu, Tadakazu ; Siegmund, Britta ; Wu, Kaichun ; Boland, Brigid S ; Melmed, Gil Y ; Armuzzi, Alessandro ; Levine, Phillip ; Kalabic, Jasmina ; Chen, Su ; Cheng, Ling ; Shu, Lei ; Duan, W. Rachel ; Pivorunas, Valerie ; Sanchez Gonzalez, Yuri ; D’Cunha, Ronilda ; Neimark, Ezequiel ; Wallace, Kori ; Atreya, Raja ; Ferrante, Marc ; Loftus, Edward V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a284t-8036061641c1fab16be8bd170bfd0dddf728d6ed1a9cfcd2b9abb71d97ea220c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Clinical trials</topic><topic>Colitis, Ulcerative - diagnosis</topic><topic>Colitis, Ulcerative - drug therapy</topic><topic>Colon - diagnostic imaging</topic><topic>Colon - drug effects</topic><topic>Colonoscopy</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Friability</topic><topic>Humans</topic><topic>Induction Chemotherapy - adverse effects</topic><topic>Induction Chemotherapy - methods</topic><topic>Inflammatory bowel disease</topic><topic>Interleukin-23 Subunit p19 - antagonists & inhibitors</topic><topic>Intestinal Mucosa - diagnostic imaging</topic><topic>Intestinal Mucosa - drug effects</topic><topic>Maintenance</topic><topic>Maintenance Chemotherapy - adverse effects</topic><topic>Maintenance Chemotherapy - methods</topic><topic>Male</topic><topic>Males</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Online First</topic><topic>Original Investigation</topic><topic>Patients</topic><topic>Placebos</topic><topic>Remission</topic><topic>Remission (Medicine)</topic><topic>Severity of Illness Index</topic><topic>Ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Louis, Edouard</creatorcontrib><creatorcontrib>Schreiber, Stefan</creatorcontrib><creatorcontrib>Panaccione, Remo</creatorcontrib><creatorcontrib>Bossuyt, Peter</creatorcontrib><creatorcontrib>Biedermann, Luc</creatorcontrib><creatorcontrib>Colombel, Jean-Frederic</creatorcontrib><creatorcontrib>Parkes, Gareth</creatorcontrib><creatorcontrib>Peyrin-Biroulet, Laurent</creatorcontrib><creatorcontrib>D’Haens, Geert</creatorcontrib><creatorcontrib>Hisamatsu, Tadakazu</creatorcontrib><creatorcontrib>Siegmund, Britta</creatorcontrib><creatorcontrib>Wu, Kaichun</creatorcontrib><creatorcontrib>Boland, Brigid S</creatorcontrib><creatorcontrib>Melmed, Gil Y</creatorcontrib><creatorcontrib>Armuzzi, Alessandro</creatorcontrib><creatorcontrib>Levine, Phillip</creatorcontrib><creatorcontrib>Kalabic, Jasmina</creatorcontrib><creatorcontrib>Chen, Su</creatorcontrib><creatorcontrib>Cheng, Ling</creatorcontrib><creatorcontrib>Shu, Lei</creatorcontrib><creatorcontrib>Duan, W. Rachel</creatorcontrib><creatorcontrib>Pivorunas, Valerie</creatorcontrib><creatorcontrib>Sanchez Gonzalez, Yuri</creatorcontrib><creatorcontrib>D’Cunha, Ronilda</creatorcontrib><creatorcontrib>Neimark, Ezequiel</creatorcontrib><creatorcontrib>Wallace, Kori</creatorcontrib><creatorcontrib>Atreya, Raja</creatorcontrib><creatorcontrib>Ferrante, Marc</creatorcontrib><creatorcontrib>Loftus, Edward V</creatorcontrib><creatorcontrib>INSPIRE and COMMAND Study Group</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JAMA : the journal of the American Medical Association</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Louis, Edouard</au><au>Schreiber, Stefan</au><au>Panaccione, Remo</au><au>Bossuyt, Peter</au><au>Biedermann, Luc</au><au>Colombel, Jean-Frederic</au><au>Parkes, Gareth</au><au>Peyrin-Biroulet, Laurent</au><au>D’Haens, Geert</au><au>Hisamatsu, Tadakazu</au><au>Siegmund, Britta</au><au>Wu, Kaichun</au><au>Boland, Brigid S</au><au>Melmed, Gil Y</au><au>Armuzzi, Alessandro</au><au>Levine, Phillip</au><au>Kalabic, Jasmina</au><au>Chen, Su</au><au>Cheng, Ling</au><au>Shu, Lei</au><au>Duan, W. Rachel</au><au>Pivorunas, Valerie</au><au>Sanchez Gonzalez, Yuri</au><au>D’Cunha, Ronilda</au><au>Neimark, Ezequiel</au><au>Wallace, Kori</au><au>Atreya, Raja</au><au>Ferrante, Marc</au><au>Loftus, Edward V</au><aucorp>INSPIRE and COMMAND Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials</atitle><jtitle>JAMA : the journal of the American Medical Association</jtitle><addtitle>JAMA</addtitle><date>2024-09-17</date><risdate>2024</risdate><volume>332</volume><issue>11</issue><spage>881</spage><epage>897</epage><pages>881-897</pages><issn>0098-7484</issn><issn>1538-3598</issn><eissn>1538-3598</eissn><abstract>IMPORTANCE: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. OBJECTIVE: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. DESIGN, SETTING, AND PARTICIPANTS: Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. INTERVENTIONS: For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. RESULTS: Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. CONCLUSION AND RELEVANCE: Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>39037800</pmid><doi>10.1001/jama.2024.12414</doi><tpages>17</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0098-7484 |
| ispartof | JAMA : the journal of the American Medical Association, 2024-09, Vol.332 (11), p.881-897 |
| issn | 0098-7484 1538-3598 1538-3598 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11264075 |
| source | MEDLINE; American Medical Association Journals (including JAMA) |
| subjects | Adult Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - adverse effects Clinical trials Colitis, Ulcerative - diagnosis Colitis, Ulcerative - drug therapy Colon - diagnostic imaging Colon - drug effects Colonoscopy Double-Blind Method Female Friability Humans Induction Chemotherapy - adverse effects Induction Chemotherapy - methods Inflammatory bowel disease Interleukin-23 Subunit p19 - antagonists & inhibitors Intestinal Mucosa - diagnostic imaging Intestinal Mucosa - drug effects Maintenance Maintenance Chemotherapy - adverse effects Maintenance Chemotherapy - methods Male Males Middle Aged Monoclonal antibodies Online First Original Investigation Patients Placebos Remission Remission (Medicine) Severity of Illness Index Ulcerative colitis |
| title | Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T17%3A02%3A11IST&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=Risankizumab%20for%20Ulcerative%20Colitis:%20Two%20Randomized%20Clinical%20Trials&rft.jtitle=JAMA%20:%20the%20journal%20of%20the%20American%20Medical%20Association&rft.au=Louis,%20Edouard&rft.aucorp=INSPIRE%20and%20COMMAND%20Study%20Group&rft.date=2024-09-17&rft.volume=332&rft.issue=11&rft.spage=881&rft.epage=897&rft.pages=881-897&rft.issn=0098-7484&rft.eissn=1538-3598&rft_id=info:doi/10.1001/jama.2024.12414&rft_dat=%3Cproquest_pubme%3E3112578317%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=3112578317&rft_id=info:pmid/39037800&rft_ama_id=2821291&rfr_iscdi=true |