title: Systematic review with meta-analysis: loss of response and requirement of anti-TNFα dose intensification in Crohn's disease.
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.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China.
authors.forename: Bai-Li
authors.initials: BL
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China.
authors.forename: Ren
authors.initials: R
authors.lastname: Mao
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China.
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zeng
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China.|IBD Service, Department of Gastroenterology, Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, 52621, Tel Hashomer, Israel.
authors.forename: Shomron
authors.initials: S
authors.lastname: Ben-Horin
authors.affiliation: 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.
authors.forename: Min-Hu
authors.initials: MH
authors.lastname: Chen
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D012074:Remission Induction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha
keywords: Anti-TNFα; Crohn’s disease; Dose intensification; Loss of response