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

Maintenance Therapy

Clinical and endoscopic steroid-free remission is the goal of therapy in UC. It is important to note that following salvage therapy, there are no controlled trials to demonstrate the effectiveness of drug therapy as a strategy to maintain remission. Aminosalicylates have been established as first-line maintenance therapy with proven efficacy in reducing relapse risk; however, in cases of persistent symptom flares, a second-line maintenance drug is required. This role traditionally has been fulfilled by thiopurines; however, infliximab has now become a viable option for maintenance therapy.[72,110] In addition, patients who receive intravenous ciclosporin salvage therapy are typically transitioned onto oral ciclosporin maintenance. However, the risk of nephrotoxicity limits the use of ciclosporin as a long-term maintenance agent, hence its use is usually limited to a 3-month duration.

Scheduled Infliximab

Although scheduled maintenance therapy with infliximab has not been evaluated following infliximab salvage therapy, it has been demonstrated to be an effective strategy in patients with chronic active moderate to severe UC despite conventional therapy (5-aminosalicylates, corticosteroids and immunosuppressants).[72] While the data on a maintenance strategy for ASUC cannot be directly extrapolated from these data, given the high rates of relapse following induction of remission with infliximab, a maintenance strategy with infliximab may be considered in some patients, particularly those who are thiopurine-experienced; however, such an approach remains to be proven.

A retrospective audit conducted across six centres in the UK found that of 38 steroid-refractory patients who received induction with infliximab, 28 (73.6%) exhibited a sustained response with 8-weekly infusions (5 mg/kg) for a mean duration of 16.8 months (range: 4–59), with 21 (55.3%) maintaining remission. Secondary loss of response after a mean duration of 10 months was seen in three patients (7.9%), while 7/38 (18.4%) patients did not respond to infliximab. Seven cases progressed to colectomy (7/38 – 18.4%) – five nonresponders and two who experienced secondary loss of response.[110] While these results are encouraging, their relevance in the ASUC setting may be limited, as only 19/38 (50%) patients satisfied Truelove and Witts' criteria for severe disease.

The UC SUCCESS out-patient trial conducted in patients with steroid-refractory UC demonstrated improved efficacy with concomitant use of infliximab and azathioprine compared to either drug in isolation.[111] Steroid-free remission rates achieved by patients who had received combination therapy at 4-month follow-up were approximately twofold greater than either monotherapy [combination: 40% (31/78), infliximab: 22% (17/77) (P = 0.017), AZA: 24% (18/76) (P = 0.032)]. Combination therapy with these two agents may be considered once patients have moved beyond the acute setting. Prospective studies evaluating the efficacy of combination therapy in ASUC is required before any definitive conclusions can be made.

Methotrexate

The success of methotrexate in induction and maintenance of remission in Crohn's disease has sparked interest in its potential use in ulcerative colitis.[112–115] A recent Cochrane review concluded that induction of remission with methotrexate is not supported by currently published literature, predominantly owing to insufficient data.[116] Retrospective data evaluating methotrexate maintenance therapy has yielded conflicting results.[117,118] More prospective trials are required to further evaluate the utility of methotrexate in maintenance of remission. Results from the METEOR trial, currently available only as an abstract, have supported the use of methotrexate as a bridge to oral therapies in steroid-dependent UC.[106] This approach awaits further evaluation.

Maintenance therapy for thiopurine-naïve patients should consist of a thiopurine; however, methotrexate may be considered in those who are thiopurine-intolerant. If there is evidence of ongoing disease activity at 3-month follow-up after salvage therapy, maintenance infliximab should be considered. Other options at this juncture include novel biological therapies, including vedolizumab and anti-MAdCAM1.[119,120] Early escalation to an intensive maintenance strategy for thiopurine-experienced patients may be necessary and scheduled infliximab may be required to maintain remission in these patients.

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