What is the Optimal Therapy for Crohn's Disease: Step-up or Top-down?

Ming Valerie Lin; Wojciech Blonski; Gary R Lichtenstein


Expert Rev Gastroenterol Hepatol. 2010;4(2):167-180. 

In This Article

Natural History of CD

The clinical course of CD is characterized by intermittent exacerbation of symptoms alternating with periods of quiescence. An inceptive cohort study from Scandinavia by Munkholm et al. demonstrated that overall, 13% of patients will achieve complete remission, 20% of patients will experience annual relapse and 67% will have a combination of relapse and remission within the first 8 years after initial diagnosis.[2] Less than 5% of patients will have a continuous course of active disease. These patients were treated with 5-ASA agents and corticosteroids (prednisolone 60–80 mg daily) during periods of disease activity. 5-ASA agents were used continuously for at least 2 years and corticosteroids were tapered down to a maintenance dose, which was withheld for no more than 2–3 months. In Silverstein et al.'s population-based cohort study, conducted prior to the routine use of anti-TNF-α, it was found that a representative patient with CD would be expected to spend 24% of the time in medical remission without medications, 41% of the time in postsurgical remission without medications, 27% of the time in medical treatment with 5-ASA derivatives and 7% of the time having disease activity mandating treatment with corticosteroids or immunomodulators.[3]

A population-based study from Olmsted County, MN, USA by Schwartz et al. demonstrated the cumulative risk for the development of Crohn's fistulas was 33% at 10 years and 50% after 20 years.[4] The authors also showed that fistula formation preceded the diagnosis of CD in approximately half of the patients.[4] The majority (83%) of fistulae required a surgical approach.[4] The clinical course of fistulae is variable and depends on their location and complexity.[5] The majority of fistulae observed in CD are external fistulae.[4,5] Perianal fistulae (abnormal connections from an internal anal opening to the external surface of perianal skin) accounted for 55% of all fistulizing complications in CD patients, whereas entero–enteric fistulae accounted for 24% and recto–vaginal fistulae accounted for 9%.[4,5] Generally, it is more difficult to achieve a closure of internal fistulae (entero–vesical or entero–enteric) with medical therapy.[5]

After medical therapy the recurrence rate of perianal fistulae has been reported to be as high as 59–71% in the referral centers[6,7] compared with 34% in the population-based study.[4] Beaugerie et al. found that the presence of perianal disease, younger age of disease onset (≤40 years old) and need for corticosteroids, were risk factors for predicting a disabling course of CD.[8] Based on this study, which was conducted in a tertiary referral center and carried the risk of referral bias, 85% of patients developed a disabling course within 5 years of diagnosis.[8]

Our current ability to predict the course of CD is still rudimentary. Although CD has been recognized as having a chronic relapsing course, it is evident that the majority of patients remain in clinical remission at any particular time. Overall, the majority of patients would progress from inflammatory to complicated fistulizing or penetrating disease over time.


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