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

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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.

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Author contributions

Acquisition of data, analysis and interpretation of data, and wrote the manuscript: Yun Qiu, Bai-li Chen; critical revision of the manuscript for important intellectual content: Ren Mao, Sheng-hong Zhang, Yao He, Zhi-rong Zeng, and Shomron Ben-Horin; study concept and design, critical revision of the manuscript for important intellectual content, statistical analysis, and study supervision: Min-hu Chen. All authors discussed the results and implications and commented on the manuscript at all stages.

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    Authors and Affiliations

    1. Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, People’s Republic of China

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

    2. IBD Service, Department of Gastroenterology, Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, 52621, Tel Hashomer, Israel

      Shomron Ben-Horin

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    1. Yun Qiu
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    2. Bai-li Chen
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    8. Min-hu Chen
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    Correspondence to Min-hu Chen.

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    The authors declare that they have no conflicts of interest.

    Financial support

    This study was financially supported in part by National Key Clinical Department in Ministry of Public Health, China (No. 303004269002) and Scientific Project of Guangzhou, China (No. 2011YZ-00004).

    Additional information

    Yun Qiu and Bai-li Chen contributed equally to this paper.

    Electronic supplementary material

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    535_2017_1324_MOESM1_ESM.tif

    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

    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

    Supplementary Table 2. Summary of subgroup analysis of anti-TNFs dose intensification among primary responders (DOCX 17 kb)

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    Cite this article

    Qiu, Y., Chen, Bl., Mao, R. et al. Systematic review with meta-analysis: loss of response and requirement of anti-TNFα dose intensification in Crohn’s disease. J Gastroenterol 52, 535–554 (2017). https://doi.org/10.1007/s00535-017-1324-3

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    • DOI: https://doi.org/10.1007/s00535-017-1324-3

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