Treat to Target

A Proposed New Paradigm for the Management of Crohn's Disease

Guillaume Bouguen; Barrett G. Levesque; Brian G. Feagan; Arthur Kavanaugh; Laurent Peyrin–Biroulet; Jean–Frederic Colombel; Stephen B. Hanauer; William J. Sandborn

Disclosures

Clin Gastroenterol Hepatol. 2015;13(6):1042-1050. 

In This Article

Abstract and Introduction

Abstract

The traditional management of Crohn's disease, which is based on progressive, step-wise treatment intensification with re-evaluation of response according to symptoms, does not improve long-term outcomes of Crohn's disease and places patients at risk for bowel damage. The introduction of novel therapies and the development of new approaches to treatment in rheumatoid arthritis led to better outcomes for patients. Prominent among these is a "treat to target" strategy that is based on regular assessment of disease activity by using objective clinical and biological outcome measures and the subsequent adjustment of treatments. This approach is complementary to the concept of early intervention in high-risk patients. This review evaluates current literature on this topic and proposes a definition for the concept of treating to targets for Crohn's disease.

Introduction

Crohn's disease (CD) is a chronic relapsing inflammatory bowel disease that frequently results in progressive segmental damage to the gastrointestinal tract.[1] Population-based studies have shown that the structural and functional bowel damage of CD is a dynamic, yet progressive process such that only 10% of patients experience prolonged remission of symptoms.[2–6] Importantly, even asymptomatic patients often have evidence of active inflammation on endoscopy, and structural bowel damage (strictures and/or fistula) identified by imaging is observed in more than 50% of patients after 10 years after diagnosis.[6,7] Consequently, even in the modern era of treatment, the majority of patients undergo surgery as a result of inadequate control of inflammation.[8]

The traditional management of CD features progressive, step-wise treatment intensification with reevaluation of response according to symptoms. Although clinically sensible, 2 fundamental problems exist with this approach. First, because it is both an incremental and time-bound paradigm, initiation of highly effective therapy (combined immunosuppression) in patients at the highest risk of disease progression is delayed. Second, because of the poor correlation that exists between symptoms and endoscopically defined disease activity, it inherently undertreats substantial proportions of patients.

In rheumatoid arthritis (RA), another chronic and debilitating immune disorder, novel treatment approaches have evolved. A major factor driving this has been the introduction of new therapies, in particular biologic agents such as tumor necrosis factor (TNF) antagonist. The clinical success of new therapies helped alter the goals of treatment, such that discussions of "remission" and achieving the lowest achievable levels of disease activity are increasingly becoming considered both possible and appropriate. It had long been recognized that persistent uncontrolled articular and systemic inflammation resulted in the harmful sequelae of RA, including joint destruction and functional disability as well as increased morbidity and even accelerated mortality. The efficacy of newer therapies reinvigorated treatment approaches to include older traditional disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate (MTX) in an effort to abrogate inflammation to the greatest extent possible. This included treatment earlier in the disease course and the use of combinations of agents such as MTX combined with a TNF antagonist.[9] A codification of these developments is the "treat to target" strategy.[10] The main principles of this strategy are based on the regular assessment of disease activity by using validated outcome measures and the subsequent adjustment of treatment in case of persistent inflammatory disease activity, preferably following a protocol where therapeutic consequences and targets are predefined (Figure 1).[11]

Figure 1.

Overview of the treat to target concept. According to risk stratification, highly effective disease-modifying therapy should first be administered to high-risk patients. Treatments should then be monitored and adjusted by using a predefined objective target.

Because of some analogies in disease course between RA and CD, the concept of treat to target that has evolved in RA can also be adapted to CD. To achieve disease modification and the prevention of structural bowel damage, an effective intervention must occur early in the course of CD (before the development of irreversible bowel damage) and adjusted to control biologic evidence of inflammation.[12,13] Although the concepts of new treatment goals such as mucosal healing (MH)[14] and deep remission[15,16] are increasingly being considered in CD patients, there is no specific definition of a treat-to-target strategy in CD that would enable these new treatment goals to be achieved. This article reviews the topic of treat to target and defines a potential treat-to-target paradigm for CD with help from available evidence and guidelines in RA.

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