Review Article

The Practical Management of Acute Severe Ulcerative Colitis

D. Seah; P. De Cruz

Disclosures

Aliment Pharmacol Ther. 2016;43(4):482-513. 

In This Article

Summary and Introduction

Summary

Background Acute severe ulcerative colitis (ASUC) is a life-threatening condition for which optimal management strategies remain ill-defined.

Aim To review the evidence regarding the natural history, diagnosis, monitoring and treatment of ASUC to inform an evidence-based approach to management.

Methods Relevant articles addressing the management of ASUC were identified from a search of MEDLINE, the Cochrane Library and conference proceedings.

Results Of ASUC, 31–35% is steroid-refractory. Infliximab and ciclosporin salvage therapies have improved patient outcomes in randomised controlled trials. Short-term response rates (within 3 months) have ranged from 40% – 54% for ciclosporin and 46–83% for infliximab. Long-term clinical response rates (≥1 year) have ranged from 42%–50% for ciclosporin and 50–65% for infliximab. Short-term and long-term colectomy rates have been respectively: 26–47% and 36–58% for ciclosporin, and 0–50% and 35–50% for infliximab. Mortality rates for ciclosporin and infliximab-treated patients have been: 0–5% and 0–2%, respectively. At present, management challenges include the selection, timing and assessment of response to salvage therapy, utilisation of therapeutic drug monitoring and long-term maintenance of remission.

Conclusions Optimal management of acute severe ulcerative colitis should be guided by risk stratification using predictive indices of corticosteroid response. Timely commencement and assessment of response to salvage therapy is critical to reducing morbidity and mortality. Emerging pharmacokinetic models and therapeutic drug monitoring may assist clinical decision-making and facilitate a shift towards individualised acute severe ulcerative colitis therapies.

Introduction

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition. The lifetime risk of a severe exacerbation requiring hospitalisation is between 15% and 25%.[1,2] Severe flares of UC are associated with considerable morbidity and a mortality rate of approximately 1%.[3] Following one or more episodes of severe flares, there is a 40% colectomy rate and one in five patients are predicted to undergo colectomy during their first hospital admission.[1,4] Long-term colectomy rates remain high, despite salvage therapies, and are thought to range from 50% to 62% at 3 years.[5,6] ASUC is diagnosed according to Truelove and Witts' criteria, which consists of bloody stool frequency ≥6 per day and at least one of the following: pulse rate >90 bpm, temperature >37.8 °C, haemoglobin <10.5 g/dL and ESR >30 mm/h (Table 1).[7] ASUC may occur in the context of varying baseline disease extent or activity. Three modes of presentation are recognised in clinical practice: (i) new-onset colitis – representing roughly one-third of the ASUC population; (ii) acute-on-chronic colitis, and (iii) relapsing and remitting patterns of disease.[1] Sixty-five to 69% of ASUC will respond adequately to intravenous corticosteroid therapy alone.[8] Salvage or rescue medical therapy may be initiated for steroid-refractory ASUC as defined by recognised clinical indices such as the Oxford criteria[7,9] (Table 2). Up to 56% of patients who fail steroid therapy require second-line salvage therapy with either infliximab or ciclosporin.[3] Although a recent multicentre randomised controlled trial showed no significant differences in the relative effectiveness of ciclosporin compared with infliximab, there is no clear consensus at this stage as to the most appropriate strategy for treating steroid-refractory ASUC.[10]

This review summarises the current evidence regarding: (i) the natural history of ASUC; (ii) diagnosis and monitoring in the ASUC setting; (iii) published studies evaluating available salvage therapy agents; (iv) predictors of nonresponse to salvage therapy; and (v) management of common precipitants and complications of ASUC. Our aim was to synthesise and integrate these data to develop a comprehensive and practical approach to ASUC management.

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