Outcomes of salvage therapy for acute severe ulcerative colitis: Cyclosporin versus Infliximab

Abstract

Acute severe ulcerative colitis (ASUC) is a common and serious complication of UC. For those cases refractory to intravenous steroid therapy Cyclosporin or, more recently, Infliximab therapy is the current standard of care. Although there have been no published studies comparing and contrasting these agents, clinical experience has previously indicated their effectiveness to be equable in this clinical context. A prospective study of 72 consecutive presentations of steroid refractory ASUC at the Royal Brisbane and Women's Hospital (RBWH) from 1996-2009 was con-ducted to assess the relative efficacy of Cyclosporin and Infliximab in this clinical setting. All study participants satisfied the Truelove and Witts criteria for acute severe colitis (≥6 bloody stools/day with one or more of the following: temperature >37.8°C; pulse rate >90/min; haemoglobin <10.5g/dl; or erythrocyte sedimentation rate (ESR) >30mm/hr) and were prevalent or incident cases of ulcerative colitis as confirmed by histological analysis. Primary endpoints measured were: outcome at discharge and outcome at 12 months after discharge; specifically whether these cases proceeded to total colectomy or were amenable to continuing medical management. The 72 steroid refractory acute colitis events were generated by 68 UC patients from north Brisbane, Queensland. Salvage therapy was instituted with either Cyclosporin in 44(61%) cases or Infliximab in the remaining 28(39%) patients. Of those patients who received Cyclosporin 52% (23/44) proceeded to total colectomy before discharge while this figure was only 18% (5/28) for those administered Infliximab as a salvage therapy. This finding was found to be statistically significant (p = 0.003). Twelve month follow-up data are currently available for 69/72 cases. At this timepoint 68% (30/44) and 44% (11/25) of cases treated with Cyclosporin and Infliximab, respectively, had required surgery for recurrent severe disease (p = 0.049). This study is of significance because it presents longitudinal outcomes data from a large, prospectively studied series of patients with refractory acute severe UC, selected on the basis of validated severity criteria. While it is clear that Infliximab salvage therapy is more efficacious than Cyclosporin in the short term in avoiding surgical intervention, the significance and duration of this benefit remain to be conclusively evaluated. We recognise that a randomised controlled trial is in progress in the United Kingdom that has been designed to answer this question and we await its findings.