Proposal for a Definition of Treat to Target in Crohn's Disease
Lessons From Rheumatoid Arthritis
Ten statements were established by an international task force that were based on 4 overarching principles: (1) shared decision-making between the patient and the rheumatologist, (2) measuring disease activity, (3) treatment to target by adjusting therapy to suppress disease activity, and (4) maximizing long-term health-related quality of life through control of symptoms, prevention of structural damage, and normalization of function and social participation. Control of disease activity and achievement of these treatment goals are done mainly through the abrogation of inflammation. The 10 statements are summarized in Table 1.
On the basis of this preliminary experience from RA, a proposal for specific recommendations can be made regarding the structure of a treat-to-target algorithm for CD as follows (Table 1 and Figure 2).
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Figure 2.
Schematic representation for a treat-to-target based strategy for CD. On the basis of preliminary experience from RA, proposal algorithm for CD includes careful selection of patients to active treatment, use of MH as the optimal target, and a time frame to assess treatment efficacy.
Patient Selection
Pending the availability of a validated prediction rule of disease outcomes, clinical markers (disease location, extent and behavior, age, severity of endoscopic ulceration, tobacco use), and possibly serologic and genetic markers should be considered for use in therapeutic decision-making after patient selection and triage of high versus low "risk" groups. Importantly, the addition of these predictors may increase the individual risk for disabling CD course and should increase the urgency for the patient to receive effective treatments.
Patient-Physician Relationship
Patients with CD need to be able to trust their physician to maximize the chance that they will adhere to an agreed on treatment strategy. Thorough discussion about the risk of the drugs versus the risks of the disease, the applicability of any prognostic markers for the individual patient, consideration of the time horizon for an individual patient, costs associated with the medications, and follow-up evaluation with laboratory studies, endoscopy, and imaging studies that might be used in a treat-to-target strategy are needed.
Definition of the Target and the Treatment
As previously described, the achievement of symptomatic remission is essential for the patient's well-being, but as a therapeutic goal, it alone does not provide optimal long-term outcomes or prevent disability.
Among the currently available objective markers of inflammation, endoscopic assessment with resolution or near-resolution of ulcer lesions is the preferred treatment target. Nevertheless, the definition of MH and the value of achieving complete MH (deep remission), in distinction to partial healing, are debated, and from a practical standpoint, many studies have defined MH as the absence of ulcers. In some instances, MRE (or possibly ultrasound) may be an alternative to endoscopy. Therapeutic targets (eg, remission versus clear improvement) may be different in patients without or with preexisting bowel damage.
Establishing a Time Frame to Assess the Target and to Institute Treatment Optimization
Collectively, these data suggest that an ideal treat-to-target strategy should follow the patient every 36 months for assessment of MH (disappearance of ulcers) with colonoscopy (or MRE or ultrasound in patients who cannot be adequately assessed with colonoscopy). In the case of persistent significant endoscopic ulceration, treatment should be further optimized to reach the predefined target of MH. Six-month intervals between colonoscopy procedures may be a reasonable compromise between selecting a time after which additional MH is unlikely to occur and a time interval between procedures that would be acceptable to patients. Finally, such targets may be useful in patients with preexisting bowel damage who have residual non–inflammatory-based symptoms to maximize long-term quality of life, while minimizing worsening of disability.
Once the predefined treatment target of MH is reached, treatment should be maintained with regular monitoring of clinical symptoms and biomarkers every 6 months and, among patients for whom other treatment options or optimization of ongoing therapy are available, regular monitoring for sustained MH every 1–2 years. A final consideration is what to do with patients who received combination therapy with a TNF antagonist and azathioprine, achieved MH, and in whom several interval colonoscopies have shown persistent MH. Can and should such patients undergo therapy de-escalation, removing either the azathioprine or the TNF antagonist? Preliminary data raise the possibility that therapy de-escalation may be possible, but the existing studies are too small to inform clinical practice. Additional data are needed to address this important issue.