Early Use of Thiopurines or Methotrexate Reduces Major Abdominal and Perianal Surgery in Crohnʼs Disease

Abstract

Early IM use with thiopurines or methotrexate was significantly associated with the reduced need for abdominal and perianal surgery in CD.

The changing face of Crohn’s disease: a population-based study of the natural history of Crohn’s disease in Örebro, Sweden 1963–2005

“…In our population-based cohort, the 5-year cumulative risk of Crohn's disease related surgery decreased from 65.8% to The decrease in surgery was not explained by an increased long-term corticosteroid use, since the 5-year cumulative probability of long-term corticosteroid treatment remained low (6-8%) throughout the study period. Higher rates of long-term corticosteroids have been reported from Cardiff, UK (29%) and Australia (59.2%), although the definition of long-term corticosteroids included budesonide, or was slightly different to our study (7,15) Interestingly, the relative proportion of patients with non-stricturing, non-penetrating (B1) disease at diagnosis who progressed to complicated behaviour was stable during our study period. Thus, the difference in disease behaviour over time was explained entirely by our previously reported increased proportion of patients in non-stricturing, non-penetrating (B1) status at diagnosis (13).…”

“…A reduction in surgical rates has been reported in Crohn's disease during recent decades, potentially due to increased use of immunomodulators and biologics (8,15,16). Especially early introduction of biologics seems to induce mucosal healing (17)(18)(19)(20), thereby theoretically inhibiting progression towards complicated disease behaviour with strictures and fistulas and ultimately reducing the need of surgery.…”

What Can We Learn from Epidemiological Studies in Inflammatory Bowel Disease?

“…However, when the influence of early immunosuppressive therapy (within 3 years after diagnosis) was analysed, a significant reduction in both first and second surgeries was found in patients starting early immunosuppressive therapy compared to those who did not (HR 0.54, 95% CI 0.37-0.79 and HR 0.44, 95% CI 0.25-0.79). Moreover, the beneficial effect of early immunosuppressive use was also found in perianal surgery; on the contrary, anti-TNFα therapy increased the risk of perianal procedures [15] . Finally, a meta-analysis of unselected cohorts focused on the role of thiopurines in need of surgical resection.…”

“…In multivariate Cox analysis disease localization, year of CD diagnosis, corticosteroid use within 3 months since diagnosis and immunosuppressive therapy were identified as independent predictors of intestinal surgery; azathioprine use within the first year of diagnosis decreased the risk of operation by approximately 50% (HR 0.47, 95% CI 0.27-0.79) [14] . On the other hand, a specialist-referred Australian cohort of CD patients diagnosed during 1970-2009 showed a significant increase in immunomodulator use over the time, but no impact of the decade of diagnosis on surgery rate [15] . However, when the influence of early immunosuppressive therapy (within 3 years after diagnosis) was analysed, a significant reduction in both first and second surgeries was found in patients starting early immunosuppressive therapy compared to those who did not (HR 0.54, 95% CI 0.37-0.79 and HR 0.44, 95% CI 0.25-0.79).…”

Medical Therapy for Crohn’s Disease: The Present

“…These studies suggest there is limited benefi t to monotherapy with thiopurines early in the course of disease, for the endpoint of steroid-free remission [ 40 ]. Long-term cohort studies have shown that early azathioprine use within 3 years of initial diagnosis was associated with a reduced risk of initial abdominal surgery (HR 0.45), recurrent abdominal surgery (HR 0.44), and perianal surgery (HR 0.30) [ 41 ]. Overall, the risk of fi rst major abdominal surgery in this cohort was 17.5 % at 1 year, 28.4 % at 5 years, and 39.5 % at 10 years.…”