Systematic review with meta-analysis: loss of response and requirement of anti-TNFα dose intensification in Crohn’s disease

  • Yun Qiu
  • Bai-li Chen
  • Ren Mao
  • Sheng-hong Zhang
  • Yao He
  • Zhi-rong Zeng
  • Shomron Ben-Horin
  • Min-hu Chen
Review

DOI: 10.1007/s00535-017-1324-3

Cite this article as:
Qiu, Y., Chen, B., Mao, R. et al. J Gastroenterol (2017). doi:10.1007/s00535-017-1324-3
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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.

Keywords

Loss of response Anti-TNFα Dose intensification Crohn’s disease 

Supplementary material

535_2017_1324_MOESM1_ESM.tif (591 kb)
Supplementary Fig. 1. Assessment of quality of randomized controlled trials using Cochrane risk of bias tool (TIFF 591 kb)
535_2017_1324_MOESM2_ESM.docx (20 kb)
Supplementary Table 1. Assessment of quality of observational studies using Newcastle Ottawa Quality Assessment Scale (NOS) (DOCX 19 kb)
535_2017_1324_MOESM3_ESM.docx (18 kb)
Supplementary Table 2. Summary of subgroup analysis of anti-TNFs dose intensification among primary responders (DOCX 17 kb)

Copyright information

© Japanese Society of Gastroenterology 2017

Authors and Affiliations

  • Yun Qiu
    • 1
  • Bai-li Chen
    • 1
  • Ren Mao
    • 1
  • Sheng-hong Zhang
    • 1
  • Yao He
    • 1
  • Zhi-rong Zeng
    • 1
  • Shomron Ben-Horin
    • 1
    • 2
  • Min-hu Chen
    • 1
  1. 1.Department of GastroenterologyThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouPeople’s Republic of China
  2. 2.IBD Service, Department of Gastroenterology, Sheba Medical Center and Sackler School of MedicineTel-Aviv UniversityTel HashomerIsrael