Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2018 May 25;12(6):635-643.
doi: 10.1093/ecco-jcc/jjy004.

Primary Non-Response to Tumor Necrosis Factor Antagonists is Associated with Inferior Response to Second-line Biologics in Patients with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis

Siddharth Singh  1   2 , John George  3 , Brigid S Boland  1 , Niels Vande Casteele  1 , William J Sandborn  1
Affiliations
Meta-Analysis

Primary Non-Response to Tumor Necrosis Factor Antagonists is Associated with Inferior Response to Second-line Biologics in Patients with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis

Siddharth Singh et al. J Crohns Colitis. .

Abstract

Background and aims: We sought to analyze whether response to a second-line biologic varies depending on the reason for discontinuation of the primary anti-TNF agent (primary non-response [PNR], secondary loss of response [LOR] after initial response, or intolerance), through a systematic review and meta-analysis.

Methods: Through a systematic search through May 31, 2017, we identified eight randomized controlled trials [RCTs] of biologics in patients with IBD with prior exposure to anti-TNF agents, that stratified response to second-line therapy by reason for discontinuing primary anti-TNF therapy [PNR vs. LOR vs. intolerance]. We estimated relative risk [RR] (and 95% confidence interval [CI]) of achieving clinical remission in patients with PNR as compared with patients with LOR, and intolerance, through random effects meta-analysis.

Results: As compared with patients who discontinued prior anti-TNF due to intolerance, patients with prior PNR were 24% less likely to achieve remission with second-line biologics (RR,0.76 [0.61-0.96]). As compared with patients who discontinued prior anti-TNF due to LOR, patients with prior PNR were 27% less likely to achieve remission with induction therapy with second-line biologics (RR,0.73 [0.56-0.97]), particularly to ustekinumab (RR,0.64 [0.52-0.80]). There was no difference in response to vedolizumab in patients with prior PNR or LOR to anti-TNF agents (RR,1.16 [0.85-1.58]).

Conclusion: Patients with PNR to anti-TNF agents are less likely to respond to second-line non-TNF biologics, as compared with patients who discontinued therapy due to secondary LOR or intolerance. This may be attributed to underlying pharmacokinetics and pharmacodynamics of anti-TNF agents in patients with PNR.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Study selection flowsheet.
Figure 2.
Figure 2.
Response to second-line biologic in patients who discontinued prior anti-TNF therapy due to [A] primary non-response vs. intolerance, [B] primary non-response vs. secondary loss of response and [C] secondary loss of response vs. intolerance. GEMINI 2 and 3, UNITI 1, CERTIFI, GAIN and WELCOME were conducted in patients with Crohn’s disease, and GEMINI 1 was conducted in patients with ulcerative colitis.
See this image and copyright information in PMC

Comment in

References

    1. Nielsen OH, Ainsworth MA. Tumor necrosis factor inhibitors for inflammatory bowel disease. N Engl J Med 2013;369:754–62. - PubMed
    1. Singh S, Pardi DS. Update on anti-tumor necrosis factor agents in Crohn disease. Gastroenterol Clin North Am 2014;43:457–78. - PubMed
    1. Sandborn WJ, Rutgeerts P, Feagan BG et al. . Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology 2009;137:1250–60; quiz 1520. - PubMed
    1. Papamichael K, Gils A, Rutgeerts P et al. . Role for therapeutic drug monitoring during induction therapy with TNF antagonists in IBD: evolution in the definition and management of primary nonresponse. Inflamm Bowel Dis 2015;21:182–97. - PubMed
    1. Gisbert JP, Marín AC, McNicholl AG, Chaparro M. Systematic review with meta-analysis: the efficacy of a second anti-TNF in patients with inflammatory bowel disease whose previous anti-TNF treatment has failed. Aliment Pharmacol Ther 2015;41:613–23. - PubMed

MeSH terms