Early aggressive therapy for severe extensive ulcerative colitis

Abstract

The current ulcerative colitis (UC) treatment algorithm involves a step-up therapeutic strategy, mainly aiming at inducing and maintaining its clinical remission. Although this therapeutic strategy may seem to be cost-efficient and reduce the risk of side effects, recent trials and case reports have shown that top-down therapy using infliximab induces a rapid clinical response, enhances patient quality of life, promotes mucosal healing, reduces surgeries and indirect cost of treatment for patients with severe UC. Moreover, since long-term treatment with infliximab is safe and well tolerated, early aggressive top-down therapeutic strategy may be a more effective approach, at least in a subgroup of severe extensive UC patients.

Key Words: Infliximab; Ulcerative colitis; Top-down therapy

INTRODUCTION

Since ulcerative colitis (UC) cannot be cured by medication,therapeutic strategy is very important for patients with UC. The UC treatment algorithm includes a early aggressive or top-down therapeutic strategy and a sequential or step-up regimen. Recently, the emergency of effective biological therapy in the treatment of UC has led to a clinical debate about “top-down vs step-up strategy”which describes two opposite approaches. Since one approach is not suitable for all patients with UC, therapeutic strategy ought to be tailored to the individual patient so as to maximize efficacy while balancing risk.and cost. In this letter the benefits, safety and costs of alternative strategies will be critically appraised.

TO THE EDITOR

I read with great interest the case report recently published in the World Journal of Gastroenterology by Cury et al[1]. The authors reported a case in which infliximab was safely and effectively administered to a patient with severe and extensive UC. Upon reading this interesting case report, two questions arose in my mind.

First, the white blood cell (WBC) count of 161 000/mm³ or 161 × 10⁹/L reported in the case, which is markedly elevated because the normal WBC concentration is 4000-10 000/mm³, remains to be elucidated. Although a high WBC count can occur in infections, toxins, acute hemolysis, trauma and malignancies, the leukocytosis described in the case report might be due to leukemoid reaction, leukemia and other myeloproliferative disorders since WBC concentration is over 30 000/mm³. However, the leukocytosis reported in the case report was not permanent and progressive, and infectious precipitants were ruled out[1]. Moreover, since no endoscopic evidence is available to support toxic megacolon, there might be an error in the WBC count or in a leukemoid reaction in the case report, the cause for which is not clear.

Second, whether top-down therapeutic strategy should be implemented in patients with severe and extensive UC which extends beyond the splenic flexure but not to the cecum. In a recently published consensus, a sequential or step-up therapy, mainly aiming at inducing and maintaining its clinical remission, has been advocated for patients with severe extensive UC which is best defined by Truelove and Witts criteria[2]. The step-up therapeutic strategy may seem to be cost-efficient for the vast majority of UC patients and reduce the risk of side effects. However, this sequential strategy did not induce mucosal healing and could not achieve the best attainable quality of life until infliximab was administered to the reported patient. In addition, early aggressive therapy with infliximab and azathioprine may reduce the indirect cost of treatment for patients. More recent studies have shown that top-down therapy using infliximab induces a rapid clinical response, has a steroid-sparing effect, enhances patient quality of life, promotes mucosal healing, and reduces hospital stay time and surgeries[3-6]. The reasons why the step-up strategy is advantageous over the top-down are concerned with its side effects and costs of biological agents. However, it was reported that long-term treatment with infliximab is safe and well tolerated and not associated with excess mortality or malignancies[5,7]. Moreover, an 8-wk maintenance treatment schedule with infliximab appears to be a cost-effective treatment option for adult patients suffering from moderate to severe UC[8]. Therefore, the top-down approach is appealing and can result in a modification in the natural course of UC, at least in a subgroup of patients with severe and extensive UC.

Since the top down approach is not suitable for all patients with UC, the future challenge is to identify a subgroup of patients who will develop complicated diseases or are therapy refractory at a later time point and for whom infliximab treatment in the early phase may change the natural history of UC.