Comparable Long-Term Outcomes of Cyclosporine and Infliximab in Patients With Steroid-Refractory Acute Severe Ulcerative Colitis: A Meta-Analysis

Abstract

Background: In steroid-refractory acute severe ulcerative colitis (ASUC), cyclosporine (CYS) or infliximab (IFX) may be considered as a second-line alternative to avoid colectomy. There are short-term data reported, but until now, there is no meta-analysis regarding long-term outcomes of CYS and IFX in patients with ASUC. Aim: To compare long-term efficacy and safety of CYS and IFX in a meta-analysis. Methods: Three electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials) were searched for studies which compared CYS vs. IFX in adults with ASUC. Long-term colectomy-free rate from 1 to 10 years during CYS or IFX therapy was collected, last updated up to 22nd May 2019. Primary outcome was long-term colectomy-free rate, secondary outcomes were adverse events (AE), serious adverse events (SAE), and mortality. Long-term colectomy-free survival and safety measures were pooled with the random-effect model. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Results: Data from 1,607 patients in 15 trials were extracted. In the first 3 years, pooled OR for colectomy-free survival was higher with IFX than with CYS (OR = 1.59, 95% CI: 1.11-2.29, p = 0.012; OR = 1.57, 95% CI: 1.14-2.18, p = 0.006; and OR = 1.75, 95% CI: 1.08-2.84, p = 0.024; at 1, 2, and 3 years, respectively). However, the significant difference remained undetected from the fourth year of followup and in subgroup of RCTs (OR = 1.35, 95% CI: 0.90-2.01, p = 0.143; OR = 1.41, 95% CI: 0.94-2.12, p = 0.096; and OR = 1.34, 95% CI: 0.89-2.00, p = 0.157; at 1, 2, and 3 years, respectively). No significant difference was detected regarding adverse events, serious adverse events and mortality between the groups. The neutral associations proved to be underpowered with trial sequential analysis. Szemes et al. Steroid-Refractory Acute Severe Ulcerative Colitis Conclusion: However observational studies show IFX as a better choice, according to the RCTs, choosing either CYS or IFX as rescue therapy for ASUC, the long-term outcomes are not different, although further large RCTs are warranted.

Ciclosporin or Infliximab as Rescue Therapy in Acute Glucorticosteroid-Refractory Ulcerative Colitis: Systematic Review and Network Meta-Analysis

“…37 Both the aforementioned meta-analyses found that there were no significant differences between infliximab and ciclosporin in terms of drug-related adverse events, serious adverse events, or mortality. 14,33 Our results also demonstrated no significant differences between the two drugs in terms of serious adverse events.…”

“…Another meta-analysis evaluating long-term outcomes of ciclosporin and infliximab in patients with acute severe UC in observational studies and RCTs reported a significantly higher colectomy-free survival rate with infliximab compared with ciclosporin. 33 This difference was only seen within the first 3 years after rescue therapy and was found in observational studies of infliximab but, importantly, not in RCTs.…”

Integrated Analysis of Multiple Microarray Studies to Identify Novel Gene Signatures in Ulcerative Colitis

“…Notably, there are dozens of ways to perform meta-analyses of different studies, and RRA is only one of them. We reviewed the current studies on ulcerative colitis (Bopanna et al, 2017;Gubatan et al, 2019;Szemes et al, 2019;Chen M. et al, 2020;Li et al, 2020;Sankarasubramanian et al, 2020;Yoon et al, 2020;de Carvalho et al, 2021;Ye et al, 2021). We believe that the advantage of RRA analysis is that more potential biomarkers can be found at one time, which can provide clues for subsequent research.…”

Management of Hospitalized Patient with Ulcerative Colitis Refractory to Corticosteroids

“…In this study, treatment failure was seen in 60% (OR 1.4) of those treated with CyA compared to 54% (OR 1.3) of those treated with IFX, with no significant difference in colectomy or serious adverse event rates [39]. In a very recent meta-analysis comparing long-term outcomes with CyA and IFX in patients with steroid-refractory ASUC, pooled odds ratio for colectomy-free survival was higher with IFX compared to CyA at 1-, 2-, and 3-year follow-up [40]. However, at the fourth year, this difference was no longer detectible.…”