Infliximab for patients with moderate to severely active ulcerative colitis: an updated meta-analysis of randomized controlled trials

Abstract

Background and aims: Ulcerative colitis (UC) is a serious inflammatory bowel disease with significant morbidity and mortality. Infliximab (IFX), a TNF-alpha antagonist, is recommended by the American Gastroenterological Association, but its clinical effectiveness and safety are based on limited studies. This meta-analysis of randomized controlled trials (RCTs) evaluates the efficacy and safety of IFX in moderate-to-severe active UC, providing evidence for its clinical application.

Methods: A systematic search of major English (PubMed, MEDLINE, Web of Science, Embase, Cochrane Library) and Chinese databases (CNKI, SinoMed, Wanfang, VIP) was conducted up to September 25, 2023, to identify RCTs comparing IFX against placebo, aminosalicylates, corticosteroids, or immunosuppressants for moderate-to-severe UC. Pooled analyses assessed short- and long-term clinical response, clinical remission, endoscopic remission (mucosal healing), safety outcomes, and corresponding 95% confidence intervals. Subgroup analyses, heterogeneity assessment, sensitivity analyses, publication bias evaluation (funnel plots), and meta-regression were performed.

Results: Twenty RCTs involving 2,350 patients (IFX: n = 1,300; controls: n = 1,050) were included. IFX demonstrated significant superior efficacy versus controls across all primary endpoints: short-term (RR = 1.38, P < 0.001) and long-term clinical response (RR = 1.52, P = 0.007); short-term (RR = 1.38, P < 0.001) and long-term clinical remission (RR = 1.52, P = 0.022); short-term (RR = 1.58, P = 0.001) and long-term endoscopic remission (RR = 1.39, P = 0.010). Adverse event rates did not differ significant between groups (RR = 1.00, P = 0.933). Meta-regression suggested geographical region as a potential source of heterogeneity for short-term clinical response.

Conclusions: IFX has a more positive effect on active UC than placebos, aminosalicylic acid preparations, steroids, or immunosuppressive drugs, but shows no superiority in terms of adverse responses.

Keywords: Evidence-based practice; Infliximab; Meta-analysis; TNF-alpha antagonists; Ulcerative colitis.

Fig. 1

PRISMA flowchart of the study selection process

Fig. 2

Quality assessment of included studies

Fig. 3

Forest plots of the RR of short-term clinical response, long-term clinical response, short-term clinical remission, and long-term clinical remission show the following: A short-term clinical response; B long-term clinical response; C short-term clinical remission; and D long-term clinical remission. All meta-analyses used random effects models

Fig. 4

Forest plot and RR for short/long-term endoscopic (mucosal) remission. A: Forest plot of short-term endoscopic remission. B: Long-term endoscopic remission

Fig. 5

Subgroup analysis of IFX dose. A: short-term clinical response; B: short-term clinical remission; C: long-term clinical response; D: long-term clinical remission. E: short-term endoscopic remission

Fig. 6

Forest plot of the meta-analysis of adverse events in the two groups

Fig. 7

Contour-enhanced funnel plot, and sensitivity analysis using the one-by-one elimination method. A: Sensitivity analysis of short-term clinical responses. B: Sensitivity analysis of short-term clinical remission. C: Contour-enhanced funnel plot of short-term clinical response. D: Contour-enhanced funnel plot of short-term clinical remission

Fig. 8

Outcome indicators evidence quality evaluation