Rescue Therapies for Steroid-refractory Acute Severe Ulcerative Colitis: A Review

J Crohns Colitis. 2023 Jun 16;17(6):972-994. doi: 10.1093/ecco-jcc/jjad004.


Background: One-third of patients with acute severe ulcerative colitis [ASUC] are steroid-refractory. We aimed to review the different options for the management of steroid-refractory ASUC, including not only the standard treatment [cyclosporine and infliximab], but also most recently developed agents [such as vedolizumab, ustekinumab, and tofacitinib].

Methods: We performed a bibliographical search to identify studies focusing on the treatment of steroid-refractory ASUC.

Results: Cyclosporine and infliximab currently represent the mainstays of salvage therapy and they are generally considered comparable. However, long-term persistence is higher in infliximab therapy, and many clinicians prefer to use infliximab given its ease of use. However, cost of cyclosporine is lower. Sequential rescue therapy after cyclosporine or infliximab failure [with infliximab and cyclosporine, respectively] could be considered in referral centres for highly selected cases. Tofacitinib, due to its rapid effect, represents an attractive rescue option mainly in biologic-experienced patients. The good safety profile of vedolizumab and ustekinumab makes them ideal candidates for use as maintenance therapy in combination with cyclosporine as induction therapy, especially for patients previously exposed to anti-TNFs or thiopurines.

Conclusions: Although cyclosporine and infliximab still represent the mainstays of salvage therapy for steroid-refractory ASUC, new therapeutic agents may also play a role. Tofacitinib, due to its rapid effect, is an attractive therapeutic rescue option. Vedolizumab and ustekinumab, as maintenance therapy in combination with the fast-acting cyclosporine as induction therapy, may represent a promising bridging strategy, especially in patients with previous failure to thiopurines and/or anti-TNF agents.

Keywords: Acute severe ulcerative colitis; anti-TNF; cyclosporine; inflammatory bowel disease; infliximab; tofacitinib; ulcerative colitis; ustekinumab; vedolizumab.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Colitis, Ulcerative* / drug therapy
  • Cyclosporine / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Infliximab / therapeutic use
  • Steroids / therapeutic use
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / therapeutic use
  • Ustekinumab / therapeutic use


  • Infliximab
  • Immunosuppressive Agents
  • Antibodies, Monoclonal
  • Ustekinumab
  • Tumor Necrosis Factor Inhibitors
  • Cyclosporine
  • Steroids