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

Abstract

BackgroundEfficacy 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.AimTo 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.MethodsPubmed, 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.ResultsEight 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).ConclusionTNF-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.

Ursolic acid protects against ulcerative colitis via anti-inflammatory and antioxidant effects in mice

“…Treatment of ulcerative colitis commonly reduces inflammatory cell infiltration and the levels of serum TNF-α and IL-1β (31,32). In particular, treatment with TNF-α neutralizing antibody or TNF-α inhibitory agents significantly improveds colitis (33,34). Therefore, suppression of these cytokines can offer an alternative therapy for ulcerative colitis.…”

Efficacy of tumour necrosis factor antagonists on remission, colectomy and hospitalisations in ulcerative colitis: Meta-analysis of placebo-controlled trials

“…Eight systematic reviews and meta-analyses had examined the efficacy of TNF antagonists in UC [10,11,[27][28][29][30][31][32]. However, the majority of them only evaluated infliximab [27][28][29][30], and only two evaluated both infliximab and adalimumab [31,32].…”

“…However, the majority of them only evaluated infliximab [27][28][29][30], and only two evaluated both infliximab and adalimumab [31,32]. The most recently evaluated in addition golimumab, more or less vedolizumab [10,11].…”

Initial experience with golimumab in clinical practice for ulcerative colitis

“…Its treatment depends on the course or behavior of the disease, and although therapy with corticosteroids, 5-aminosalicylates, and immunomodulators is effective in most cases, biological agents as anti-tumor necrosis factors (TNF) are necessary in cases where the disease is refractory or intolerant to therapeutic agents (1). The consequence of treatment failure in UC patients is a greater number of colectomies, and a possible alternative therapy in UC patients is a TNF-blocking agent, which has been shown to be effective, inducing clinical response and remission, and reducing the need for colectomy (2,3).…”