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2. HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis

Author

Akar, Alaa, Flemming, Cornelius, Felix, Flomm, Flosbach, Markus, Jäger, Julia, Jeromin, Niklas, Jung, Johannes, Ohms, Mareike, Reinshagen, Konrad, Rische, Johann, Sagebiel, Adrian, Sandfort, Deborah, Steinert, Fenja, Tomuschat, Christian, Wesche, Jasmin, Shifteh Abedian, Abraham, Clara, Achkar, Jean-Paul, Ahmad, Tariq, Alberts, Rudi, Alizadeh, Behrooz, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Anderson, Carl A., Andrews, Jane M., Annese, Vito, Aumais, Guy, Baidoo, Leonard, Baldassano, Robert N., Bampton, Peter A., Barclay, Murray, Barrett, Jeffrey C., Bethge, Johannes, Bewshea, Claire, Bis, Joshua C., Bitton, Alain, BK, Thelma, Boucher, Gabrielle, Brain, Oliver, Brand, Stephan, Brant, Steven R., Cheon, Jae Hee, Chew, Angela, Cho, Judy H., Cleynen, Isabelle, Cohain, Ariella, Cooney, Rachel, Croft, Anthony, Daly, Mark J., D'Amato, Mauro, Danese, Silvio, Daryani, Naser Ebrahim, Datta, Lisa Wu, Degenhardt, Frauke, Denapiene, Goda, Denson, Lee A., Devaney, Kathy L., Dewit, Olivier, D'Inca, Renata, Drummond, Hazel E., Dubinsky, Marla, Duerr, Richard H., Edwards, Cathryn, Ellinghaus, David, Ellul, Pierre, Esaki, Motohiro, Essers, Jonah, Ferguson, Lynnette R., Festen, Eleonora A., Fleshner, Philip, Florin, Tim, Franchimont, Denis, Franke, Andre, Fuyuno, Yuta, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Goyette, Philippe, Green, Todd, Griffiths, Anne M., Guthery, Stephen L., Hakonarson, Hakon, Halfvarson, Jonas, Hanigan, Katherine, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hayward, Nicholas K., Hedl, Matija, Henderson, Paul, Hold, Georgina L., Hong, Myhunghee, Hu, Xinli, Huang, Hailiang, Hugot, Jean-Pierre, Hui, Ken Y., Imielinski, Marcin, Jazayeri, Omid, Jonaitis, Laimas, Jostins, Luke, Juyal, Garima, Chandra Juyal, Ramesh, Kalla, Rahul, Karlsen, Tom H., Kennedy, Nicholas A., Khan, Mohammed Azam, Kim, Won Ho, Kitazono, Takanari, Kiudelis, Gediminas, Kubo, Michiaki, Kugathasan, Subra, Kupcinskas, Limas, Lamb, Christopher A., de Lange, Katrina M., Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lee, James C., Lees, Charlie W., Leja, Marcis, Lewis, Nina, Van Limbergen, Johan, Lionetti, Paolo, Liu, Jimmy Z., Louis, Edouard, Luo, Yang, Mahy, Gillian, Malekzadeh, Masoud Mohammad, Malekzadeh, Reza, Mansfield, John, Marriott, Suzie, Massey, Dunecan, Mathew, Christopher G., Matsui, Toshiyuki, McGovern, Dermot P.B., van der Meulen, Andrea, Midha, Vandana, Milgrom, Raquel, Mirzaei, Samaneh, Mitrovic, Mitja, Montgomery, Grant W., Mowat, Craig, Müller, Christoph, Newman, William G., Ng, Aylwin, Ng, Siew C., Evelyn Ng, Sok Meng, Nikolaus, Susanna, Ning, Kaida, Nöthen, Markus, Oikonomou, Ioannis, Okou, David, Orchard, Timothy R., Palmieri, Orazio, Parkes, Miles, Phillips, Anne, Ponsioen, Cyriel Y., Potocnik, Urõs, Poustchi, Hossein, Prescott, Natalie J., Proctor, Deborah D., Radford-Smith, Graham, Rahier, Jean- Francois, Regueiro, Miguel, Reinisch, Walter, Rieder, Florian, Rioux, John D., Roberts, Rebecca, Rogler, Gerhard, Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schadt, Eric E., Scharl, Michael, Schembri, John, Schreiber, Stefan, Schumm, L. Philip, Scott, Regan, Seielstad, Mark, Shah, Tejas, Sharma, Yashoda, Silverberg, Mark S., Simmons, Alison, Simms, Lisa A., Singh, Abhey, Skieceviciene, Jurgita, van Sommeren, Suzanne, Song, Kyuyoung, Sood, Ajit, Spain, Sarah L., Steinhart, A. Hillary, Stempak, Joanne M., Stronati, Laura, Sung, Joseph J.Y., Targan, Stephan R., Taylor, Kirstin M., Theatre, Emilie, Torkvist, Leif, Torres, Esther A., Tremelling, Mark, Uhlig, Holm H., Umeno, Junji, Vahedi, Homayon, Vasiliauskas, Eric, Velde, Anje ter, Ventham, Nicholas T., Vermeire, Severine, Verspaget, Hein W., De Vos, Martine, Walters, Thomas, Wang, Kai, Wang, Ming-Hsi, Weersma, Rinse K., Wei, Zhi, Whiteman, David, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Wong, Sunny H., Xavier, Ramnik J., Yamazaki, Keiko, Yang, Suk-Kyun, Ye, Byong Duk, Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhang, Hu, Zhang, Wei, Zhao, Hongyu, Zhao, Zhen Z., Baumdick, Martin E., Niehrs, Annika, Schwerk, Maria, Hinrichs, Ole, Jordan-Paiz, Ana, Padoan, Benedetta, Wegner, Lucy H.M., Schloer, Sebastian, Zecher, Britta F., Malsy, Jakob, Joshi, Vinita R., Illig, Christin, Schröder-Schwarz, Jennifer, Möller, Kimberly J., Martin, Maureen P., Yuki, Yuko, Ozawa, Mikki, Sauter, Jürgen, Schmidt, Alexander H., Perez, Daniel, Giannou, Anastasios D., Carrington, Mary, Davis, Randall S., Schumacher, Udo, Sauter, Guido, Huber, Samuel, Puelles, Victor G., Melling, Nathaniel, Altfeld, Marcus, and Bunders, Madeleine J.

Published
2023
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4. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Author

Jostins, Luke, Ripke, Stephan, Weersma, Rinse K, Duerr, Richard H, McGovern, Dermot P, Hui, Ken Y, Lee, James C, Philip Schumm, L, Sharma, Yashoda, Anderson, Carl A, Essers, Jonah, Mitrovic, Mitja, Ning, Kaida, Cleynen, Isabelle, Theatre, Emilie, Spain, Sarah L, Raychaudhuri, Soumya, Goyette, Philippe, Wei, Zhi, Abraham, Clara, Achkar, Jean-Paul, Ahmad, Tariq, Amininejad, Leila, Ananthakrishnan, Ashwin N, Andersen, Vibeke, Andrews, Jane M, Baidoo, Leonard, Balschun, Tobias, Bampton, Peter A, Bitton, Alain, Boucher, Gabrielle, Brand, Stephan, Büning, Carsten, Cohain, Ariella, Cichon, Sven, D’Amato, Mauro, De Jong, Dirk, Devaney, Kathy L, Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Ferguson, Lynnette R, Franchimont, Denis, Fransen, Karin, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hedl, Matija, Hu, Xinli, Karlsen, Tom H, Kupcinskas, Limas, Kugathasan, Subra, Latiano, Anna, Laukens, Debby, Lawrance, Ian C, Lees, Charlie W, Louis, Edouard, Mahy, Gillian, Mansfield, John, Morgan, Angharad R, Mowat, Craig, Newman, William, Palmieri, Orazio, Ponsioen, Cyriel Y, Potocnik, Uros, Prescott, Natalie J, Regueiro, Miguel, Rotter, Jerome I, Russell, Richard K, Sanderson, Jeremy D, Sans, Miquel, Satsangi, Jack, Schreiber, Stefan, Simms, Lisa A, Sventoraityte, Jurgita, Targan, Stephan R, Taylor, Kent D, Tremelling, Mark, Verspaget, Hein W, De Vos, Martine, Wijmenga, Cisca, Wilson, David C, Winkelmann, Juliane, Xavier, Ramnik J, Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K, Zhao, Hongyu, Silverberg, Mark S, Annese, Vito, Hakonarson, Hakon, Brant, Steven R, Radford-Smith, Graham, Mathew, Christopher G, Rioux, John D, and Schadt, Eric E

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Digestive Diseases, Human Genome, Inflammatory Bowel Disease, Biotechnology, Autoimmune Disease, Crohn's Disease, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Oral and gastrointestinal, Colitis, Ulcerative, Crohn Disease, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Haplotypes, Host-Pathogen Interactions, Humans, Inflammatory Bowel Diseases, Mycobacterium, Mycobacterium Infections, Mycobacterium tuberculosis, Phenotype, Polymorphism, Single Nucleotide, Reproducibility of Results, International IBD Genetics Consortium, General Science & Technology
Abstract

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

Published
2012

6. Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes

Author

Julsgaard, Mette, Hvas, Christian L, Gearry, Richard B, Gibson, Peter R, Fallingborg, Jan, Sparrow, Miles P, Bibby, Bo M, Connell, William R, Brown, Steven J, Kamm, Michael A, Lawrance, Ian C, Vestergaard, Thea, Svenningsen, Lise, Baekdal, Mille, Kammerlander, Heidi, Walsh, Alissa, Boysen, Trine, Bampton, Peter, Radford-Smith, Graham, Kjeldsen, Jens, Andrews, Jane M, Subramaniam, Kavitha, Moore, Gregory T, Jensen, Nanna M, Connor, Susan J, Wildt, Signe, Wilson, Benedicte, Ellard, Kathrine, Christensen, Lisbet A, and Bell, Sally J

Published
2020
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8. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

Author

Cleynen, Isabelle, Boucher, Gabrielle, Jostins, Luke, Schumm, L Philip, Zeissig, Sebastian, Ahmad, Tariq, Andersen, Vibeke, Andrews, Jane M, Annese, Vito, Brand, Stephan, Brant, Steven R, Cho, Judy H, Daly, Mark J, Dubinsky, Marla, Duerr, Richard H, Ferguson, Lynnette R, Franke, Andre, Gearry, Richard B, Goyette, Philippe, Hakonarson, Hakon, Halfvarson, Jonas, Hov, Johannes R, Huang, Hailang, Kennedy, Nicholas A, Kupcinskas, Limas, Lawrance, Ian C, Lee, James C, Satsangi, Jack, Schreiber, Stephan, Théâtre, Emilie, van der Meulen-de Jong, Andrea E, Weersma, Rinse K, Wilson, David C, Parkes, Miles, Vermeire, Severine, Rioux, John D, Mansfield, John, Silverberg, Mark S, Radford-Smith, Graham, McGovern, Dermot P B, Barrett, Jeffrey C, and Lees, Charlie W

Published
2016
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9. Crohn's disease management after intestinal resection: a randomised trial

Author

De Cruz, Peter, Kamm, Michael A, Hamilton, Amy L, Ritchie, Kathryn J, Krejany, Efrosinia O, Gorelik, Alexandra, Liew, Danny, Prideaux, Lani, Lawrance, Ian C, Andrews, Jane M, Bampton, Peter A, Gibson, Peter R, Sparrow, Miles, Leong, Rupert W, Florin, Timothy H, Gearry, Richard B, Radford-Smith, Graham, Macrae, Finlay A, Debinski, Henry, Selby, Warwick, Kronborg, Ian, Johnston, Michael J, Woods, Rodney, Elliott, P Ross, Bell, Sally J, Brown, Steven J, Connell, William R, and Desmond, Paul V

Published
2015
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10. An Extremes of Phenotype Approach Confirms Significant Genetic Heterogeneity in Patients with Ulcerative Colitis

Author

Mortlock, Sally, primary, Lord, Anton, additional, Montgomery, Grant, additional, Zakrzewski, Martha, additional, Simms, Lisa A, additional, Krishnaprasad, Krupa, additional, Hanigan, Katherine, additional, Doecke, James D, additional, Walsh, Alissa, additional, Lawrance, Ian C, additional, Bampton, Peter A, additional, Andrews, Jane M, additional, Mahy, Gillian, additional, Connor, Susan J, additional, Sparrow, Miles P, additional, Bell, Sally, additional, Florin, Timothy H, additional, Begun, Jakob, additional, Gearry, Richard B, additional, and Radford-Smith, Graham L, additional

Published
2022
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12. Relationship between disease severity and quality of life and assessment of health care utilization and cost for ulcerative colitis in Australia: A cross-sectional, observational study

Author

Gibson, Peter R., Vaizey, Carolynne, Black, Christopher M., Nicholls, Rebecca, Weston, Adèle R., Bampton, Peter, Sparrow, Miles, Lawrance, Ian C., Selby, Warwick S., Andrews, Jane M., Walsh, Alissa J., Hetzel, David J., Macrae, Finlay A., Moore, Gregory T., Weltman, Martin D., Leong, Rupert W., and Fan, Tao

Published
2014
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13. Nonsynonymous Polymorphism in Guanine Monophosphate Synthetase Is a Risk Factor for Unfavorable Thiopurine Metabolite Ratios in Patients With Inflammatory Bowel Disease

Author

Roberts, Rebecca L, Wallace, Mary C, Seinen, Margien L, van Bodegraven, Adriaan A, Krishnaprasad, Krupa, Jones, Gregory T, van Rij, Andre M, Baird, Angela, Lawrance, Ian C, Prosser, Ruth, Bampton, Peter, Grafton, Rachel, Simms, Lisa A, Studd, Corrie, Bell, Sally J, Kennedy, Martin A, Halliwell, Jacob, Gearry, Richard B, Radford-Smith, Graham, Andrews, Jane M, McHugh, Patrick C, and Barclay, Murray L

Published
2018
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19. Inter-observer agreement for Crohn's disease sub-phenotypes using the Montreal Classification: How good are we? A multi-centre Australasian study

Author

Krishnaprasad, Krupa, Andrews, Jane M., Lawrance, Ian C., Florin, Timothy, Gearry, Richard B., Leong, Rupert W.L., Mahy, Gillian, Bampton, Peter, Prosser, Ruth, Leach, Peta, Chitti, Laurie, Cock, Charles, Grafton, Rachel, Croft, Anthony R., Cooke, Sharon, Doecke, James D., and Radford-Smith, Graham L.

Published
2012
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21. Tu1891 THE REAL-WORLD USE OF FIVE-AMINOSALICYLATE (5ASA) TREATMENT FOR ULCERATIVE COLITIS IN AUSTRALIA AND NEW ZEALAND: CROHN'S COLITIS CURE (CCC) DATA INSIGHT'S PROGRAM

Author

Pipicella, Joseph L., McNamara, Jack, Wilson, William E., Lynch, Kate D., Walker, Gareth J., Begun, Jakob, Lawrance, Ian C., Ghaly, Simon, Radford-Smith, Graham L., Williams, Astrid-Jane, Gearry, Richard, Schultz, Michael, Brett, Laurel, Andrews, Jane M., and Connor, Susan J.

Published
2024
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26. An Extremes of Phenotype Approach Confirms Significant Genetic Heterogeneity in Patients with Ulcerative Colitis.

Author

Mortlock, Sally, Lord, Anton, Montgomery, Grant, Zakrzewski, Martha, Simms, Lisa A, Krishnaprasad, Krupa, Hanigan, Katherine, Doecke, James D, Walsh, Alissa, Lawrance, Ian C, Bampton, Peter A, Andrews, Jane M, Mahy, Gillian, Connor, Susan J, Sparrow, Miles P, Bell, Sally, Florin, Timothy H, Begun, Jakob, Gearry, Richard B, and Radford-Smith, Graham L

Abstract

Background and Aims Ulcerative colitis [UC] is a major form of inflammatory bowel disease globally. Phenotypic heterogeneity is defined by several variables including age of onset and disease extent. The genetics of disease severity remains poorly understood. To further investigate this, we performed a genome wide association [GWA] study using an extremes of phenotype strategy. Methods We conducted GWA analyses in 311 patients with medically refractory UC [MRUC], 287 with non-medically refractory UC [non-MRUC] and 583 controls. Odds ratios [ORs] were calculated for known risk variants comparing MRUC and non-MRUC, and controls. Results MRUC–control analysis had the greatest yield of genome-wide significant single nucleotide polymorphisms [SNPs] [2018], including lead SNP = rs111838972 [OR = 1.82, p = 6.28 × 10−9] near MMEL1 and a locus in the human leukocyte antigen [HLA] region [lead SNP = rs144717024, OR = 12.23, p = 1.7 × 10−19]. ORs for the lead SNPs were significantly higher in MRUC compared to non-MRUC [ p < 9.0 × 10−6]. No SNPs reached significance in the non-MRUC–control analysis (top SNP, rs7680780 [OR 2.70, p = 5.56 × 10−8). We replicate findings for rs4151651 in the Complement Factor B [CFB] gene and demonstrate significant changes in CFB gene expression in active UC. Detailed HLA analyses support the strong associations with MHC II genes, particularly HLA-DQA1 , HLA-DQB1 and HLA-DRB1 in MRUC. Conclusions Our MRUC subgroup replicates multiple known UC risk variants in contrast to non-MRUC and demonstrates significant differences in effect sizes compared to those published. Non-MRUC cases demonstrate lower ORs similar to those published. Additional risk and prognostic loci may be identified by targeted recruitment of individuals with severe disease. [ABSTRACT FROM AUTHOR]

Published
2023
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28. An extremes of phenotype approach confirms significant genetic heterogeneity in patients with ulcerative colitis

Author

Mortlock, Sally, primary, Lord, Anton, additional, Montgomery, Grant, additional, Zakrzewski, Martha, additional, Simms, Lisa A., additional, Krishnaprasad, Krupa, additional, Hanigan, Katherine, additional, Doecke, James D., additional, Walsh, Alissa, additional, Lawrance, Ian C, additional, Bampton, Peter A., additional, Andrews, Jane M., additional, Mahy, Gillian, additional, Connor, Susan J., additional, Sparrow, Miles P, additional, Bell, Sally, additional, Florin, Timothy H, additional, Begun, Jakob, additional, Gearry, Richard B, additional, and Radford-Smith, Graham L., additional

Published
2021
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30. Fine-mapping inflammatory bowel disease loci to single-variant resolution

Author

Huang, Hailiang, Fang, Ming, Jostins, Luke, Umievi Mirkov, Maa, Boucher, Gabrielle, Anderson, Carl A., Andersen, Vibeke, Cleynen, Isabelle, Cortes, Adrian, Crins, Franois, DAmato, Mauro, Deffontaine, Valrie, Dmitrieva, Julia, Docampo, Elisa, Elansary, Mahmoud, Farh, Kyle Kai-How, Franke, Andre, Gori, Ann-Stephan, Goyette, Philippe, Halfvarson, Jonas, Haritunians, Talin, Knight, Jo, Lawrance, Ian C., Lees, Charlie W., Louis, Edouard, Mariman, Rob, Meuwissen, Theo, Mni, Myriam, Momozawa, Yukihide, Parkes, Miles, Spain, Sarah L., Thtre, Emilie, Trynka, Gosia, Satsangi, Jack, van Sommeren, Suzanne, Vermeire, Severine, Xavier, Ramnik J., Weersma, Rinse K., Duerr, Richard H., Mathew, Christopher G., Rioux, John D., McGovern, Dermot P. B., Cho, Judy H., Georges, Michel, Daly, Mark J., and Barrett, Jeffrey C.

Subjects
Inflammatory bowel diseases -- Genetic aspects, Quantitative trait loci -- Health aspects, Genetic variation -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Inflammatory bowel diseases are chronic gastrointestinal inflammatory disorders that affect millions of people worldwide. Genome-wide association studies have identified 200 inflammatory bowel disease-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals. We pinpoint 18 associations to a single causal variant with greater than 95% certainty, and an additional 27 associations to a single variant with greater than 50% certainty. These 45 variants are significantly enriched for protein-coding changes (n=13), direct disruption of transcription-factor binding sites (n=3), and tissue-specific epigenetic marks (n=10), with the last category showing enrichment in specific immune cells among associations stronger in Crohns disease and in gut mucosa among associations stronger in ulcerative colitis. The results of this study suggest that high-resolution fine-mapping in large samples can convert many discoveries from genome-wide association studies into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms., Author(s): Hailiang Huang (corresponding author) [1, 2]; Ming Fang [3, 4]; Luke Jostins [5, 6]; Maa Umievi Mirkov [7]; Gabrielle Boucher [8]; Carl A. Anderson [7]; Vibeke Andersen [9, 10]; [...]

Published
2017
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31. Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease:Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes

Author

Julsgaard, Mette, Hvas, Christian L, Gearry, Richard B, Gibson, Peter R, Fallingborg, Jan, Sparrow, Miles P, Bibby, Bo M, Connell, William R, Brown, Steven J, Kamm, Michael A, Lawrance, Ian C, Vestergaard, Thea, Svenningsen, Lise, Baekdal, Mille, Kammerlander, Heidi, Walsh, Alissa, Boysen, Trine, Bampton, Peter, Radford-Smith, Graham, Kjeldsen, Jens, Andrews, Jane M, Subramaniam, Kavitha, Moore, Gregory T, Jensen, Nanna M, Connor, Susan J, Wildt, Signe, Wilson, Benedicte, Ellard, Kathrine, Christensen, Lisbet A, Bell, Sally J, Julsgaard, Mette, Hvas, Christian L, Gearry, Richard B, Gibson, Peter R, Fallingborg, Jan, Sparrow, Miles P, Bibby, Bo M, Connell, William R, Brown, Steven J, Kamm, Michael A, Lawrance, Ian C, Vestergaard, Thea, Svenningsen, Lise, Baekdal, Mille, Kammerlander, Heidi, Walsh, Alissa, Boysen, Trine, Bampton, Peter, Radford-Smith, Graham, Kjeldsen, Jens, Andrews, Jane M, Subramaniam, Kavitha, Moore, Gregory T, Jensen, Nanna M, Connor, Susan J, Wildt, Signe, Wilson, Benedicte, Ellard, Kathrine, Christensen, Lisbet A, and Bell, Sally J

Abstract

BACKGROUND: Active inflammatory bowel disease (IBD) adversely affects pregnancy outcomes. Little is known about the risk of relapse after stopping anti-tumor necrosis factor (anti-TNF) treatment during pregnancy. We assessed the risk of relapse before delivery in women who discontinued anti-TNF treatment before gestational week (GW) 30, predictors of reduced infant birth weight, a marker associated with long-term adverse outcomes, and rates and satisfaction with counseling.METHODS: Pregnant women with IBD receiving anti-TNF treatment were prospectively invited to participate in an electronic questionnaire carried out in 22 hospitals in Denmark, Australia, and New Zealand from 2011 to 2015. Risk estimates were calculated, and birth weight was investigated using t tests and linear regression.RESULTS: Of 175 women invited, 153 (87%) responded. In women in remission, the relapse rate did not differ significantly between those who discontinued anti-TNF before GW 30 (1/46, 2%) compared with those who continued treatment (8/74, 11%; relative risk, 0.20; 95% confidence interval [CI], 0.02 to 1.56; P = 0.08). Relapse (P = 0.001) and continuation of anti-TNF therapy after GW 30 (P = 0.007) were independently associated with reduced mean birth weight by 367 g (95% CI, 145 to 589 g; relapse) and 274 g (95% CI, 77 to 471 g; anti-TNF exposure after GW 30). Of 134 (88%) women who received counseling, 116 (87%) were satisfied with the information provided.CONCLUSIONS: To minimize fetal exposure in women in remission, discontinuation of anti-TNF before GW 30 seems safe. Relapse and continuation of anti-TNF therapy after GW 30 were each independently associated with lower birth weight, although without an increased risk for birth weight <2500 g. Most women received and were satisfied with counseling.

Published
2020

33. Natalizumab induction and maintenance therapy for Crohn's disease

Author

Sandborn, William J., Colombel, Jean Frederic, Enns, Roberts, Feagan, Brian G., Hanauer, Stephen B., Lawrance, Ian C., Panaccione, Remo, Sanders, Martin, Schreiber, Stefan, Targan, Stephen, van Deventer, Sander, Goldblum, Ronald, Despain, Darrin, Hogge, Gary S., and Rutgeerts, Paul

Subjects
Crohn's disease -- Research
Abstract

Two controlled experiments are carried out to examine natalizumab as induction and maintenance treatments in patients suffering from active Crohn's disease. Findings indicate that for Crohn's disease, induction therapy with natalizumab produced small insignificant improvements in response and remission rates.

Published
2005

36. Clinical risk stratification accurately predicts development of endoscopic recurrence after Crohnʼs disease surgery: early results from the prospective POCER study

Author

DE CRUZ, PETER, KAMM, MICHAEL A, HAMILTON, AMY, RITCHIE, KATHRYN, KREJANY, SOULA, GORELIK, ALEXANDRA, LIEW, DANNY, LAWRANCE, IAN C, ANDREWS, JANE, BAMPTON, PETER, SPARROW, MILES, JAKOBOVITS, SIMON, FLORIN, TIMOTHY, GIBSON, PETER, DEBINSKI, HENRY, GEARRY, RICHARD, MACRAE, FINLAY, LEONG, RUPERT W, KRONBORG, IAN, RADFORD-SMITH, GRAHAM, CONNELL, WILLIAM, BROWN, STEVEN, BELL, SALLY, ELLIOTT, ROSS, and DESMOND, PAUL

Published
2012

37. Adalimumab prevents post-operative Crohnʼs disease recurrence, and is superior to thiopurines: early results from the POCER study

Author

DE CRUZ, PETER, KAMM, MICHAEL A, HAMILTON, AMY, RITCHIE, KATHRYN, KREJANY, SOULA, GORELIK, ALEXANDRA, LIEW, DANNY, LAWRANCE, IAN C, ANDREWS, JANE, BAMPTON, PETER, SPARROW, MILES, JAKOBOVITS, SIMON, FLORIN, TIMOTHY, GIBSON, PETER, DEBINSKI, HENRY, GEARRY, RICHARD, MACRAE, FINLAY, LEONG, RUPERT W, KRONBORG, IAN, RADFORD-SMITH, GRAHAM, CONNELL, WILLIAM, BROWN, STEVEN, BELL, SALLY, ELLIOTT, ROSS, and DESMOND, PAUL

Published
2012

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