Letter: should colectomy be the end‐point to evaluate the effectiveness of drug therapies in severe ulcerative colitis?

Abstract

SIRS, We read with interest the study of Saito et al. in which predictors of response to i.v. ciclosporin in steroid-refractory, severe, ulcerative colitis (UC) were evaluated. The study provides additional data strengthening the idea that the more severe is disease activity at baseline or soon after starting ciclosporin therapy (as reflected by a persistently high Lichtiger score or a decrease in total serum protein concentration) the poorer is the outcome. 3 However, some methodological issues might limit the application of their proposed score and decision tree. First, the study deals with a highly selected population with severe disease activity, despite i.v. corticosteroids (Lichtiger score >9), which is not the usual clinical scenario when rescue therapies, such as ciclosporin or infliximab, are used in UC patients. In addition, an outstanding proportion of patients in the study presented additional factors for unresponsive disease, such as cytomegalovirus reactivation, Clostridium difficile disease or unsuccessful attempts with other rescue therapies (infliximab or leukocytoapheresis) prior to ciclosporin therapy. Second, all patients were treated with i.v corticosteroids for at least 5 days; despite they all had persistent severe activity. Finally, the authors chose to define response to ciclosporin as the avoidance of colectomy within the following 3 months. Nowadays, when clinical experience with calcineurinic antagonists and anti-TNF agents in UC is wide, 5 therapeutic decisions should be taken in a timely manner to improve drug efficacy and clinical outcomes. Two prospective studies showed that response to corticosteroid therapy in UC is accurately predicted after third day 8 and, therefore, corticosteroid therapy should not be further prolonged, particularly, in severely ill patients. Early introduction of rescue therapies not only may improve their efficacy, but also could allow administering sequential therapies in safer conditions. In this sense, not the need of colectomy, but rather the need for rescue therapies should be the end-point for predictive studies in steroid-refractory UC. In fact, 35% of the patients in the study by Saito et al. achieved a partial response after 14 days of ciclosporin therapy, and some of them were not colectomised, but had to prolong ciclosporin treatment or were switched to leukocytoapheresis, meaning that ciclosporin failed, although colectomy was not performed.