2e98ad666fafdab78ebd42a85afa9255 pmc_34209880.pdf 8f92973c744bb569e48d8865767ff936a960d5b9 pmc_34209880.pdf d4d9375f1af2d61d112402f49a5cd8dbe5adf917c4cc56e26f7a32d369894f2a pmc_34209880.pdf Title: Effectiveness of Third-Class Biologic Treatment in Crohn’s Disease: A Multi-Center Retrospective Cohort Study Subject: Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent. Keywords: Crohn’s disease; anti-TNF failure; treatment response; treatment failure; ustekinumab; vedolizumab Author: Ahmad Albshesh, Joshua Taylor, Edoardo V. Savarino, Marie Truyens, Alessandro Armuzzi, Davide G. Ribaldone, Ariella Bar-Gil Shitrit, Morine Fibelman, Pauliina Molander, Claire Liefferinckx, Stephane Nancey, Mohamed Korani, Mariann Rutka, Manuel Barreiro-de Acosta, Viktor Domislovic, Gerard Suris, Carl Eriksson, Catarina Alves, Afroditi Mpitouli, Caroline di Jiang, Katja Tepeš, Marina Coletta, Kalliopi Foteinogiannopoulou, Javier P. Gisbert, Hadar Amir-Barak, Mohamed Attauabi, Jakob Seidelin, Waqqas Afif, Carla Marinelli, Triana Lobaton, Daniela Pugliese, Nitsan Maharshak, Anneline Cremer, Jimmy K. Limdi, Tamás Molnár, Borja Otero-Alvarin, Zeljko Krznaric, Fernando Magro, Konstantinos Karmiris, Tim Raine, David Drobne, Ioannis Koutroubakis, Maria Chaparro, Henit Yanai, Johan Burisch and Uri Kopylov Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Jul 7 11:26:34 2021 CEST ModDate: Wed Jul 7 11:30:19 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1185744 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- UWUJQC+VnURWPalladioL Type 1 Custom yes yes no 10 0 DVNGCC+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 RLMFLY+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 RKSDRW+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 AIQCCL+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 39 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 61 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 65 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 69 0 IKKWKP+CMSY10 Type 1 Builtin yes yes no 84 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 91 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 95 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:11:51 CEST RepresentationInformation: pmc_34209880.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:14:24 CEST Size: 1185744 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 295 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Patient Population Destination: subsection.2.1 Item: Title: Clinical Scores and Outcomes Destination: subsection.2.2 Item: Title: Statistical Methods Destination: subsection.2.3 Item: Title: Results Destination: section.3 Children: Item: Title: Baseline Characteristics Destination: subsection.3.1 Item: Title: Treatment Outcomes Destination: subsection.3.2 Children: Item: Title: Induction Period (Weeks 16 22) Destination: subsubsection.3.2.1 Item: Title: Maintenance (Week 52) Destination: subsubsection.3.2.2 Item: Title: Treatment Discontinuation Destination: subsubsection.3.2.3 Item: Title: Safety Destination: subsubsection.3.2.4 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: section.4 Info: Title: Effectiveness of Third-Class Biologic Treatment in Crohn’s Disease: A Multi-Center Retrospective Cohort Study Author: Ahmad Albshesh, Joshua Taylor, Edoardo V. Savarino, Marie Truyens, Alessandro Armuzzi, Davide G. Ribaldone, Ariella Bar-Gil Shitrit, Morine Fibelman, Pauliina Molander, Claire Liefferinckx, Stephane Nancey, Mohamed Korani, Mariann Rutka, Manuel Barreiro-de Acosta, Viktor Domislovic, Gerard Suris, Carl Eriksson, Catarina Alves, Afroditi Mpitouli, Caroline di Jiang, Katja Tepeš, Marina Coletta, Kalliopi Foteinogiannopoulou, Javier P. Gisbert, Hadar Amir-Barak, Mohamed Attauabi, Jakob Seidelin, Waqqas Afif, Carla Marinelli, Triana Lobaton, Daniela Pugliese, Nitsan Maharshak, Anneline Cremer, Jimmy K. Limdi, Tamás Molnár, Borja Otero-Alvarin, Zeljko Krznaric, Fernando Magro, Konstantinos Karmiris, Tim Raine, David Drobne, Ioannis Koutroubakis, Maria Chaparro, Henit Yanai, Johan Burisch and Uri Kopylov Subject: Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16 22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent. Keywords: Crohn’s disease; anti-TNF failure; treatment response; treatment failure; ustekinumab; vedolizumab Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Jul 07 11:26:34 CEST 2021 ModDate: Wed Jul 07 11:30:19 CEST 2021 ID: 0x129fcb2af04dfc1c0f276cb989810e63, 0x129fcb2af04dfc1c0f276cb989810e63 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: RLMFLY+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 154 FontDescriptor: FontName: RLMFLY+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: IKKWKP+CMSY10 FontSubset: true FirstChar: 20 LastChar: 21 FontDescriptor: FontName: IKKWKP+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: RKSDRW+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 246 FontDescriptor: FontName: RKSDRW+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: UWUJQC+VnURWPalladioL FontSubset: true FirstChar: 160 LastChar: 226 FontDescriptor: FontName: UWUJQC+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: OVNEXW+EURM10 FontSubset: true FirstChar: 22 LastChar: 22 FontDescriptor: FontName: OVNEXW+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: AIQCCL+VnURWPalladioL-Bold FontSubset: true FirstChar: 161 LastChar: 161 FontDescriptor: FontName: AIQCCL+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: DVNGCC+URWPalladioL-Ital FontSubset: true FirstChar: 3 LastChar: 119 FontDescriptor: FontName: DVNGCC+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: WBVKDJ+URWPalladioL-BoldItal FontSubset: true FirstChar: 112 LastChar: 112 FontDescriptor: FontName: WBVKDJ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 35, 759, 176, 795 Annotation: Subtype: Link Rect: 515, 759, 560, 795 Annotation: Subtype: Link Rect: 127, 659, 138, 673 Annotation: Subtype: Link Rect: 138, 648, 149, 661 Annotation: Subtype: Link Rect: 464, 634, 475, 648 Annotation: Subtype: Link Rect: 280, 622, 291, 635 Annotation: Subtype: Link Rect: 429, 609, 440, 623 Annotation: Subtype: Link Rect: 527, 609, 538, 623 Annotation: Subtype: Link Rect: 234, 597, 245, 610 Annotation: Subtype: Link Rect: 393, 597, 404, 610 Annotation: Subtype: Link Rect: 110, 584, 121, 598 Annotation: Subtype: Link Rect: 304, 572, 315, 585 Annotation: Subtype: Link Rect: 376, 559, 387, 573 Annotation: Subtype: Link Rect: 534, 559, 545, 573 Annotation: Subtype: Link Rect: 99, 346, 154, 355 Annotation: Subtype: Link Rect: 35, 334, 102, 343 Annotation: Subtype: Link Rect: 35, 162, 97, 184 Annotation: Subtype: Link Rect: 153, 89, 154, 98 Annotation: Subtype: Link Rect: 35, 77, 147, 86 Annotation: Subtype: Link Rect: 131, 17, 268, 28 Annotation: Subtype: Link Rect: 422, 17, 558, 28 Annotation: Subtype: Link Rect: 35, 458, 87, 477 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 380, 212, 387, 221 ActionDest: 126 Annotation: Subtype: Link Rect: 388, 212, 395, 221 ActionDest: 126 Annotation: Subtype: Link Rect: 209, 174, 216, 183 ActionDest: 126 Annotation: Subtype: Link Rect: 216, 174, 223, 183 ActionDest: 126 Annotation: Subtype: Link Rect: 311, 149, 318, 158 ActionDest: 126 Annotation: Subtype: Link Rect: 321, 149, 333, 158 ActionDest: 130 Annotation: Subtype: Link Rect: 483, 136, 490, 145 ActionDest: 126 Annotation: Subtype: Link Rect: 379, 99, 391, 108 ActionDest: 130 Annotation: Subtype: Link Rect: 392, 98, 403, 108 ActionDest: 130 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 358, 735, 370, 744 ActionDest: 130 Annotation: Subtype: Link Rect: 544, 722, 556, 731 ActionDest: 130 Annotation: Subtype: Link Rect: 552, 217, 559, 226 ActionDest: 88 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 462, 223, 469, 235 ActionDest: 99 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 465, 376, 472, 388 ActionDest: 99 Annotation: Subtype: Link Rect: 331, 351, 338, 363 ActionDest: 99 Annotation: Subtype: Link Rect: 200, 313, 207, 325 ActionDest: 99 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 391, 707, 398, 719 ActionDest: 108 Annotation: Subtype: Link Rect: 390, 325, 397, 337 ActionDest: 99 Annotation: Subtype: Link Rect: 200, 287, 207, 299 ActionDest: 99 Annotation: Subtype: Link Rect: 435, 275, 442, 287 ActionDest: 99 Annotation: Subtype: Link Rect: 425, 237, 432, 249 ActionDest: 99 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 520, 641, 527, 653 ActionDest: 111 Annotation: Subtype: Link Rect: 253, 200, 260, 211 ActionDest: 108 Annotation: Subtype: Link Rect: 203, 136, 210, 148 ActionDest: 117 Annotation: Subtype: Link Rect: 241, 126, 248, 136 ActionDest: 117 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 393, 301, 405, 310 ActionDest: 130 Annotation: Subtype: Link Rect: 405, 301, 417, 310 ActionDest: 130 Annotation: Subtype: Link Rect: 418, 301, 430, 310 ActionDest: 130 Annotation: Subtype: Link Rect: 269, 276, 281, 285 ActionDest: 126 Annotation: Subtype: Link Rect: 281, 276, 293, 285 ActionDest: 130 Annotation: Subtype: Link Rect: 296, 276, 308, 285 ActionDest: 133 Annotation: Subtype: Link Rect: 269, 213, 281, 222 ActionDest: 130 Annotation: Subtype: Link Rect: 281, 213, 293, 222 ActionDest: 130 Annotation: Subtype: Link Rect: 294, 213, 306, 222 ActionDest: 130 Annotation: Subtype: Link Rect: 306, 213, 318, 222 ActionDest: 133 Annotation: Subtype: Link Rect: 502, 201, 514, 210 ActionDest: 126 Annotation: Subtype: Link Rect: 515, 201, 527, 210 ActionDest: 133 Annotation: Subtype: Link Rect: 527, 201, 539, 210 ActionDest: 133 Annotation: Subtype: Link Rect: 317, 163, 329, 172 ActionDest: 130 Annotation: Subtype: Link Rect: 329, 163, 341, 172 ActionDest: 133 Annotation: Subtype: Link Rect: 344, 163, 356, 172 ActionDest: 133 Annotation: Subtype: Link Rect: 516, 88, 528, 97 ActionDest: 126 Annotation: Subtype: Link Rect: 529, 88, 541, 97 ActionDest: 133 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 328, 722, 340, 731 ActionDest: 130 Annotation: Subtype: Link Rect: 340, 722, 352, 731 ActionDest: 130 Annotation: Subtype: Link Rect: 474, 685, 486, 694 ActionDest: 133 Annotation: Subtype: Link Rect: 486, 685, 498, 694 ActionDest: 133 Annotation: Subtype: Link Rect: 233, 634, 245, 643 ActionDest: 133 Annotation: Subtype: Link Rect: 485, 634, 497, 643 ActionDest: 133 Annotation: Subtype: Link Rect: 497, 634, 509, 643 ActionDest: 133 Page: Sequence: 10 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 339, 567, 376, 578 Annotation: Subtype: Link Rect: 256, 545, 293, 555 Annotation: Subtype: Link Rect: 131, 522, 169, 532 Annotation: Subtype: Link Rect: 99, 499, 137, 509 Annotation: Subtype: Link Rect: 352, 463, 389, 474 Annotation: Subtype: Link Rect: 131, 430, 169, 440 Annotation: Subtype: Link Rect: 291, 407, 329, 417 Annotation: Subtype: Link Rect: 335, 407, 371, 417 Annotation: Subtype: Link Rect: 195, 372, 233, 382 Annotation: Subtype: Link Rect: 239, 372, 275, 382 Annotation: Subtype: Link Rect: 251, 337, 289, 348 Annotation: Subtype: Link Rect: 238, 302, 276, 313 Annotation: Subtype: Link Rect: 282, 302, 318, 313 Annotation: Subtype: Link Rect: 59, 269, 97, 279 Annotation: Subtype: Link Rect: 103, 269, 139, 279 Annotation: Subtype: Link Rect: 494, 245, 531, 256 Annotation: Subtype: Link Rect: 435, 210, 472, 221 Annotation: Subtype: Link Rect: 478, 210, 514, 221 Annotation: Subtype: Link Rect: 95, 188, 133, 198 Annotation: Subtype: Link Rect: 139, 188, 175, 198 Annotation: Subtype: Link Rect: 104, 154, 141, 164 Annotation: Subtype: Link Rect: 148, 154, 184, 164 Annotation: Subtype: Link Rect: 297, 119, 334, 129 Annotation: Subtype: Link Rect: 391, 84, 429, 95 Annotation: Subtype: Link Rect: 435, 84, 471, 95 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 258, 709, 295, 720 Annotation: Subtype: Link Rect: 270, 675, 307, 686 Annotation: Subtype: Link Rect: 73, 641, 110, 651 Annotation: Subtype: Link Rect: 194, 607, 231, 617 Annotation: Subtype: Link Rect: 238, 607, 274, 617 Annotation: Subtype: Link Rect: 338, 571, 376, 582 Annotation: Subtype: Link Rect: 193, 537, 230, 548 Annotation: Subtype: Link Rect: 428, 502, 465, 513 Annotation: Subtype: Link Rect: 95, 469, 133, 479 Annotation: Subtype: Link Rect: 205, 434, 242, 444 Annotation: Subtype: Link Rect: 249, 434, 285, 444 Annotation: Subtype: Link Rect: 502, 399, 540, 410 Annotation: Subtype: Link Rect: 196, 365, 233, 375 Annotation: Subtype: Link Rect: 240, 365, 276, 375 Annotation: Subtype: Link Rect: 249, 330, 287, 341 Annotation: Subtype: Link Rect: 59, 296, 97, 306 Annotation: Subtype: Link Rect: 95, 262, 133, 272 Annotation: Subtype: Link Rect: 309, 238, 347, 249 Annotation: Subtype: Link Rect: 272, 192, 309, 203 Annotation: Subtype: Link Rect: 326, 157, 364, 168 Annotation: Subtype: Link Rect: 168, 123, 205, 134 Annotation: Subtype: Link Rect: 212, 123, 248, 134 Annotation: Subtype: Link Rect: 59, 89, 97, 99 Annotation: Subtype: Link Rect: 103, 89, 139, 99 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 205, 709, 242, 720 Annotation: Subtype: Link Rect: 323, 675, 360, 686 Annotation: Subtype: Link Rect: 152, 641, 190, 651 Annotation: Subtype: Link Rect: 319, 606, 357, 617 Annotation: Subtype: Link Rect: 363, 606, 399, 617 Annotation: Subtype: Link Rect: 391, 571, 429, 582 Annotation: Subtype: Link Rect: 456, 548, 494, 559 Annotation: Subtype: Link Rect: 500, 548, 536, 559 Annotation: Subtype: Link Rect: 216, 514, 254, 525 Annotation: Subtype: Link Rect: 260, 514, 296, 525 Annotation: Subtype: Link Rect: 368, 491, 405, 502 Annotation: Subtype: Link Rect: 389, 456, 426, 467 Annotation: Subtype: Link Rect: 432, 456, 468, 467 Annotation: Subtype: Link Rect: 366, 422, 404, 433 Annotation: Subtype: Link Rect: 440, 387, 478, 398 Annotation: Subtype: Link Rect: 484, 387, 520, 398 Annotation: Subtype: Link Rect: 59, 354, 97, 364 Annotation: Subtype: Link Rect: 103, 354, 139, 364 Annotation: Subtype: Link Rect: 158, 319, 195, 329 Checksum: 1d217bfb Type: CRC32 Checksum: 2e98ad666fafdab78ebd42a85afa9255 Type: MD5 Checksum: 8f92973c744bb569e48d8865767ff936a960d5b9 Type: SHA-1 Checksum: d4d9375f1af2d61d112402f49a5cd8dbe5adf917c4cc56e26f7a32d369894f2a Type: SHA-256