Top-down approach to biological therapy of Crohn’s disease

ABSTRACT

Introduction: Crohn’s disease (CD) is a chronic, immune-mediated condition with a potentially disabling and destructive course. Despite growing data on when to use a therapeutic ‘top-down’ strategy, clinical management of this complex disorder is still challenging. Currently, the discussion of ‘top-down’ strategy in CD mostly includes biological therapy alone or in combination.

Areas covered: This article is based on a review of existing literature regarding the use of biological therapy in a ‘top-down’ approach for the treatment of Crohn’s disease. The authors reviewed all the major databases including MEDLINE as well as DDW and ECCO abstracts, respectively.

Expert opinion: A ‘top-down’ therapeutic approach in Crohn’s disease is strongly supported by existing data in patients with several risk factors for a severe course of disease. Moreover, there is an increasing amount of published data recommending a more individualised therapeutic strategy to identify candidates for ‘top-down’ treatment, based on enhanced diagnostics using biomarkers. Emerging therapeutic approaches besides existing therapy concepts using biologicals may possibly redefine the ‘top-down’ therapeutic strategy for Crohn’s disease in the future.

KEYWORDS:

• Crohn´s disease
• IBD
• mucosal healing
• colitis
• prognosis
• individualized therapy

Article highlights

• Pharmacotherapy in Crohn’s disease has to be tailored to the individual patient, depending on several factors including the localization and activity of the disease, existing risk factors for a poor prognosis and patient preference

• Mucosal healing is associated with a superior clinical outcome (higher percentage of steroid-free remission, lower rate of hospitalization and surgery) in IBD and aAnti-TNF antibodies are currently the most effective drug class to induce and maintain mucosal healing

• Patients with risk factors for a complicated course of disease (such as smoking, deep ulcers in endoscopy or a fistulizing disease course) might benefit most from a ‘top-down’ strategy to avoid cumulative tissue damage

• Early anti-TNF-therapy (particularly in patients with a CD-duration < 2 years, as shown in the CHARM and ADHERE clinical trials) is associated with a higher efficacy in terms of maintaining remission

• According to the IBSEN study, 43% of CD patients show a mild course of disease with no need for an aggressive immunosuppressive treatment, Rogler [1] considers only 10% or less of the CD patients having a need for biological therapy

• The traditional ‘top-down’ approach to biological therapy will change with upcoming new substances towards a more individualized therapy regimen including oral applications and molecular diagnostics forecasting individual response to the treatment

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript has not been funded.