Yun Qiu1, Bai-Li Chen1, Ren Mao1, Sheng-Hong Zhang1, Yao He1, Zhi-Rong Zeng1, Shomron Ben-Horin1,2, Min-Hu Chen3. 1. Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China. 2. IBD Service, Department of Gastroenterology, Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, 52621, Tel Hashomer, Israel. 3. Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China. chenminhu@vip.163.com.
Abstract
BACKGROUND: To review the frequency with which anti-TNF-α loses its effect and dose "intensification" is required for Crohn's disease (CD) treatment. METHODS: Electronic databases were searched for eligible studies. Raw data from studies meeting inclusion criteria were pooled for effect estimates. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes. RESULTS: Eighty-six eligible studies were included. Estimates of loss of response (LOR) incidence ranged from 8 to 71%. The random effects pooled incidence of LOR with a median follow-up of 1-year was 33% (95% CI 29-38, 55 studies, n = 6135). The effect estimate based on data from patients with infliximab was 33% (95% CI 27-40), 30% (95% CI 22-39) for adalimumab, and 41% (95% CI 30-53) for certolizumabpegol. Overall, the mean percentage of patients' LOR to anti-TNFs was 38.5%. The annual risk for LOR was 20.9% per patient-year. The random-effects pooled rate of need for dose intensification with a median follow-up of 1 year was 34% (95% CI 28-41, 38 studies, n = 10,690). The effect estimate for infliximab was 38% (95% CI 28-50), 36% (95% CI 30-43) for adalimumab, and 2% (95% CI 2-3) for certolizumab-pegol. The mean percentage of patients who needed an anti-TNF dose escalation was 23% with an annual risk of 18.5% per patient-year. There was no evidence of publication bias for incidence of LOR but not for the dose intensification (p = 0.001). CONCLUSIONS: Overall, around one-third of CD patients experience a LOR and required dose intensification in primary anti-TNF-α responders.
BACKGROUND: To review the frequency with which anti-TNF-α loses its effect and dose "intensification" is required for Crohn's disease (CD) treatment. METHODS: Electronic databases were searched for eligible studies. Raw data from studies meeting inclusion criteria were pooled for effect estimates. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes. RESULTS: Eighty-six eligible studies were included. Estimates of loss of response (LOR) incidence ranged from 8 to 71%. The random effects pooled incidence of LOR with a median follow-up of 1-year was 33% (95% CI 29-38, 55 studies, n = 6135). The effect estimate based on data from patients with infliximab was 33% (95% CI 27-40), 30% (95% CI 22-39) for adalimumab, and 41% (95% CI 30-53) for certolizumabpegol. Overall, the mean percentage of patients' LOR to anti-TNFs was 38.5%. The annual risk for LOR was 20.9% per patient-year. The random-effects pooled rate of need for dose intensification with a median follow-up of 1 year was 34% (95% CI 28-41, 38 studies, n = 10,690). The effect estimate for infliximab was 38% (95% CI 28-50), 36% (95% CI 30-43) for adalimumab, and 2% (95% CI 2-3) for certolizumab-pegol. The mean percentage of patients who needed an anti-TNF dose escalation was 23% with an annual risk of 18.5% per patient-year. There was no evidence of publication bias for incidence of LOR but not for the dose intensification (p = 0.001). CONCLUSIONS: Overall, around one-third of CDpatients experience a LOR and required dose intensification in primary anti-TNF-α responders.
Entities:
Keywords:
Anti-TNFα; Crohn’s disease; Dose intensification; Loss of response
Authors: Richard J Farrell; Mazen Alsahli; Yoon-Tae Jeen; Kenneth R Falchuk; Mark A Peppercorn; Pierre Michetti Journal: Gastroenterology Date: 2003-04 Impact factor: 22.682
Authors: Uri Kopylov; Talal Al-Taweel; Mohammad Yaghoobi; Benedicte Nauche; Alain Bitton; Peter L Lakatos; Shomron Ben-Horin; Waqqas Afif; Ernest G Seidman Journal: J Crohns Colitis Date: 2014-07-25 Impact factor: 9.071
Authors: Stephen B Hanauer; Brian G Feagan; Gary R Lichtenstein; Lloyd F Mayer; S Schreiber; Jean Frederic Colombel; Daniel Rachmilewitz; Douglas C Wolf; Allan Olson; Weihang Bao; Paul Rutgeerts Journal: Lancet Date: 2002-05-04 Impact factor: 79.321
Authors: Daan W Hommes; Brenda H van de Heisteeg; Mirjam van der Spek; Joep F W M Bartelsman; Sander J H van Deventer Journal: Inflamm Bowel Dis Date: 2002-03 Impact factor: 5.325
Authors: Johannan F Brandse; Charlotte P Peters; Krisztina B Gecse; Emma J Eshuis; Jeroen M Jansen; Hans A Tuynman; Mark Löwenberg; Cyriel Y Ponsioen; Gijs R van den Brink; Geert R DʼHaens Journal: Inflamm Bowel Dis Date: 2014-02 Impact factor: 5.325
Authors: R Panaccione; J-F Colombel; W J Sandborn; G D'Haens; Q Zhou; P F Pollack; R B Thakkar; A M Robinson Journal: Aliment Pharmacol Ther Date: 2013-09-22 Impact factor: 8.171
Authors: Gerard E Kaiko; Feidi Chen; Chin-Wen Lai; I-Ling Chiang; Jacqueline Perrigoue; Aleksandar Stojmirović; Katherine Li; Brian D Muegge; Umang Jain; Kelli L VanDussen; Bridie J Goggins; Simon Keely; Jessica Weaver; Paul S Foster; Daniel A Lawrence; Ta-Chiang Liu; Thaddeus S Stappenbeck Journal: Sci Transl Med Date: 2019-03-06 Impact factor: 17.956
Authors: Eugenia Shmidt; Gursimran Kochhar; Justin Hartke; Prianka Chilukuri; Joseph Meserve; Khadija Chaudrey; Jenna L Koliani-Pace; Robert Hirten; David Faleck; Morris Barocas; Michelle Luo; Karen Lasch; Brigid S Boland; Siddharth Singh; Niels Vande Casteele; Sashidhar Varma Sagi; Monika Fischer; Shannon Chang; Matthew Bohm; Dana Lukin; Keith Sultan; Arun Swaminath; David Hudesman; Nitin Gupta; Sunanda Kane; Edward V Loftus; William J Sandborn; Corey A Siegel; Bruce E Sands; Jean-Frederic Colombel; Bo Shen; Parambir S Dulai Journal: Inflamm Bowel Dis Date: 2018-10-12 Impact factor: 5.325
Authors: Jacob E Ollech; Inessa Normatov; Noam Peleg; Jingzhou Wang; Shivani A Patel; Victoria Rai; Yangtian Yi; Jorie Singer; Sushila R Dalal; Atsushi Sakuraba; Russell D Cohen; David T Rubin; Joel Pekow Journal: Clin Gastroenterol Hepatol Date: 2020-02-26 Impact factor: 11.382
Authors: James K Stone; Leigh Anne Shafer; Lesley A Graff; Lisa Lix; Kelcie Witges; Laura E Targownik; Clove Haviva; Kathryn Sexton; Charles N Bernstein Journal: Inflamm Bowel Dis Date: 2021-02-16 Impact factor: 5.325