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What “Treat-to-Target” Could Look Like in Crohn’s Management

June 30, 2015 7:00 am

A recent study (treat to target full text -Bouguen G et al. Clin Gastroenterol Hepatol 2015; 13: 1042-50) proposes a “new paradigm for the management of Crohn’s disease.” The concept of treating-to-target has been discussed in several previous blogs:

The concern with the traditional management has been ongoing damage to the bowel in many patients and lack of optimizing long-term outcomes. The authors in the report make the following points:

Only 10% of Crohn’s disease (CD) patients experience prolonged remission of symptoms
Even asymptomatic patients often have evidence of active inflammation on endoscopy
The majority of patients will require surgery
Two big obstacles: delay in initiation of highly effective therapy (eg. combined biologic/immunosuppressant) and underestimation of disease activity due to poor correlation of symptoms to actual disease activity

While the fact that the majority of patients are at risk, some populations are at increased risk including the following:

those who smoke cigarettes
patients younger than 40 years at diagnosis
stricturing or penetrating disease
need for surgery
inability to wean corticosteroids
deep ulcerations on endoscopy

However, the authors note that “the lack of adequate data in this area of research makes risk stratification very difficult in clinical practice.” The authors review several studies:

ACCENT-I
Step-Up Top-Down trial
IBSEN population-based cohort study
SONIC
The Leuven cohort study
EXTEND trial

The data from these studies is used to base their argument of pursuing mucosal healing/more aggressive treatment, though they acknowledge that one risk is potentially subjecting some patients to overtreatment. The review indicates that mucosal healing (MH) is defined endoscopically as “the disappearance of ulceration” and that endoscopy is the tool for testing for MH for the near-term, but that other markers including MRE and surrogate biomarkers may be useful alternatives.

The authors’ Table 1 list their proposed recommendations for CD, modeled after similar recommendations for Rheumatoid Arthritis. The Four Key points:

The physician and patient need to agree on the treatment target strategy
The primary target for treatment of CD should be absence of endoscopic ulceration
The use of both clinical symptoms and objective measures of inflammation (endoscopic or imaging) is required in routine clinical practice to guide treatment decisions
Until the desired treatment target is reached, MH should be assessed every 6 months until the disappearance of ulceration and every 1-2 years thereafter. Drug therapy should be adjusted accordingly.

Limitations on this strategy:

Cost of assessment–both endoscopy and MRE are expensive
Cost of therapies
While MH can be achieved in a higher percentage of patients, there are some patients who will not respond to any of the currently available therapies
Risk of therapies. Some patients will develop adverse effects from the available therapies which will limit their therapeutic options.
This proposed strategy has very limited data in clinical practice

Take-home message from the authors: The “natural history” is not likely to improve unless the overall, symptom-based, therapeutic strategy for CD is changed.