Personalizing Therapy for Inflammatory Bowel Diseases

Ashwin N Ananthakrishnan


Expert Rev Gastroenterol Hepatol. 2013;7(6):549-558. 

In This Article

Can Current Therapies Change Natural History of IBD?

Hospitalizations and surgery are key events in the natural history of IBD and are responsible for a substantial portion of the disease-related morbidity. It is intuitive that as use of effective therapies increases, we should witness a corresponding decrease in disease-related surgeries and hospitalizations. However until recently, there were limited data supporting such secular trends. National hospitalization-based databases in the USA suggested an increasing number of hospitalizations and surgeries for both CD and UC over the past decade.[18,19] An elegant French study by Cosnes et al. found that despite increasing use of thiopurines, there was no reduction in CD-related surgery.[20] Interpretation of this study is confounded by the fact that sicker patients are more likely to be started on immunosuppressive agents, and once substantial bowel damage has occurred, medical therapy may not be able to prevent the eventual outcome. Indeed, the latter may be a likely explanation for the lack of reduction in surgeries in the pre-biologics era.

Recent population-based cohorts have suggested that we are indeed witnessing a reduction in the rates of surgery on a societal level. Lakatos et al. examined trends in IBD-related surgeries from a population-based cohort in western Hungary.[21] Between 1977 and 2008, the probability of initiating AZA 5 years after a diagnosis of CD increased from 6 to 46%. While there was no overall reduction in the rate of intestinal surgery across the three time periods, early exposure to AZA was associated with a significant reduction in the need for intestinal surgery (hazard ratio [HR]: 0.43). In a population-based cohort from Cardiff, Ramadas et al. similarly showed that not only had the use of AZA increased from 1986, but the cumulative rates of surgery for patients with CD diagnosed after 1998 was significantly lower than for those diagnosed prior to 1991 (25 vs 59%; p = 0.001).[22] In a longer-term follow-up of a large cohort of CD patients treated with AZA for a median of 13 years, responders to AZA also had a reduction in the need for perianal surgery (odds ratio [OR]: 0.36; 95% CI: 0.27–0.46).[23]

Analyses of two population-based cohorts of UC patients in Canada found lower rates of colectomy than historically reported and a secular decrease in need for colectomy across both cohorts.[24,25] Interestingly, when stratifying by indication of colectomy, Kaplan et al. found that while there has been a significant reduction in elective colectomy, the rates of emergent colectomy remained the same[24] supporting other analyses suggesting that the outcomes of the sickest cohort of patients has remained unchanged.[26] Whether this is a reflection of our inability to alter the natural history in the subset with most severe disease or delayed use of effective therapies remains unclear.