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Meta-Analysis
, 9 (1), e86692
eCollection

Tumor Necrosis Factor Alpha Blocking Agents as Treatment for Ulcerative Colitis Intolerant or Refractory to Conventional Medical Therapy: A Meta-Analysis

Affiliations
Meta-Analysis

Tumor Necrosis Factor Alpha Blocking Agents as Treatment for Ulcerative Colitis Intolerant or Refractory to Conventional Medical Therapy: A Meta-Analysis

Ruxi Lv et al. PLoS One.

Abstract

Background: Efficacy of tumor necrosis factor alpha (TNF-α) blockers for treatment of ulcerative colitis that is unresponsive to conventional therapy is unclear due to recent studies yielding conflicting results.

Aim: To assess the efficacy and safety of anti-TNF-α agents for treatment of ulcerative colitis patients who were intolerant or refractory to conventional medical therapy.

Methods: Pubmed, Embase, and the Cochrane database were searched. Analysis was performed on randomized controlled trials that assessed anti-TNF-α therapy on ulcerative colitis patients that had previously failed therapy with corticosteroids and/or immunosuppressants. The primary outcome focused on was the frequency of patients that achieved clinical remission. Further trial outcomes of interest included rates of remission without patient use of corticosteroids during the trial, extent of mucosal healing, and the number of cases that resulted in colectomy and serious side effects.

Results: Eight trials from seven studies (n = 2122) met the inclusion criteria and were thus included during analysis. TNF-α blockers demonstrated clinical benefit as compared to placebo control as evidenced by an increased frequency of clinical remission (p<0.00001), steroid-free remission (p = 0.01), endoscopic remission (p<0.00001) and a decrease in frequency of colectomy (p = 0.03). No difference was found concerning serious side effects (p = 0.05). Three small trials (n = 57) comparing infliximab to corticosteroid treatment, showed no difference in frequency of clinical remission (p = 0.93), mucosal healing (p = 0.80), and requirement for a colectomy (p = 0.49). One trial compared infliximab to cyclosporine (n = 115), wherein no difference was found in terms of mucosal healing (p = 0.85), colectomy frequency (p = 0.60) and serious side effects (p = 0.23).

Conclusion: TNF-α blockers are effective and safe therapies for the induction and maintenance of long-term remission and prevention of treatment by colectomy for patients with refractory ulcerative colitis where conventional treatment was previously ineffective. Furthermore, infliximab and cyclosporine were found to be comparable for treating acute severe steroid-refractory ulcerative colitis.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Study flow diagram.
Figure 2
Figure 2. Risk of bias summary: review of authors' judgements about each risk of bias item for included studies.
Figure 3
Figure 3. Risk of bias graph: review of authors' judgements about each risk of bias item presented as percentages across all included studies.
Figure 4
Figure 4. Pooled outcome for clinical remission in patients exposed to TNF-α blocker vs. controls.
Figure 5
Figure 5. Pooled outcome for mucosal healing in patients exposed to TNF-α blocker vs. controls.
Figure 6
Figure 6. Pooled outcome for steroid-free remission in patients exposed to TNF-α blocker vs. controls.
Figure 7
Figure 7. Pooled outcome for colectomy rate in patients exposed to TNF-α blocker vs. controls.
Figure 8
Figure 8. Pooled outcome for serious side effects in patients exposed to TNF-α blocker vs. controls.

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Grant support

This study was funded by National Natural Science Foundation of China, grant number [No. 81173240]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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