Mucosal healing was seen in 51% of patients in this setting treated

with infliximab. In the recent UC SUCCESS trial enrolling patients who had failed steroids and were not on azathioprine; mucosal healing and steroid free remission was more likely among patients treated with infliximab based therapies than azathioprine.35 There is a suggestion that male gender,36 initial response to steroids37 and a shorter extent of disease38 are predictors of response. Some recent evidence suggests adalimumab is also effective in the induction and maintenance of clinical remission in this setting.39,40 While anti-TNF therapy is available in Europe and North America check details for this indication, it is not yet available in the Asia-Pacific region.6 Cost-effectiveness of maintenance biological agent versus proctocolectomy in UC remains a consideration but this should take into account indirect costs and the risk of peri- and postoperative complications including pouchitis associated with surgical management. Acute severe ulcerative colitis.  Infliximab has been studied as an alternative to surgery or cyclosporine in one prospective randomized trial of patients with acute severe colitis. Following the failure of conventional therapy, 45 patients randomized to infliximab or placebo demonstrated a reduced colectomy rate at 3 months of 29% and 67%, respectively.11 The durability

of this effect is unknown and the subject of further investigation. Recent retrospective local data suggest using infliximab in acute severe colitis results in a lower colectomy rate (21 vs 63% at 3 months) with some durability of this response at 12 months.41 This study also indicates longer Opaganib hospital stays in patients administered cyclosporine. These data conflict with the multicenter European CYSIF

study, which suggested equivalence between infliximab and cyclosporine for acute severe colitis, with a more rapid onset of improvement in the cyclosporine group.42 Top-down versus step-up.  Inversion of the conventional model of use of biological agents (their use when non-biologic therapies have failed) is termed the “top-down” approach. When used earlier in the course of disease, biological agents may reduce the need for corticosteroids, improve mucosal healing and change the natural history of the disease, avoiding development of strictures and fistulae.43,44 A recent trial comparing a Dichloromethane dehalogenase “top-down approach” of azathioprine combined with infliximab (3-dose induction, then episodic infusions for further flares), against conventional “step-up therapy” (corticosteroids, then azathioprine and then infliximab as required for further flares) has yielded promising results.45 Rates of remission were higher and rates of corticosteroid use and relapse were improved over a year when using a top-down approach. The top-down approach also improved mucosal healing (73% vs 30%); those who achieved mucosal healing from this cohort had increased rates of steroid-free remission.