Is top-down therapy a more effective alternative to conventional step-up therapy for Crohn's disease?

Abstract

The management of Crohn's disease involves immunosuppressive protocols in a step-up approach that progresses through a therapeutic pyramid with several tiers of medication. Medications at the top are considered more potent but present greater risk. A new top-down approach to therapy inverts this procedure, using top-tier drugs for initial treatment. A critical appraisal of the current literature relating to top-down therapy was performed to evaluate its merit. A literature search was conducted on PubMed, Ovid, and PubMed Central to identify studies of the efficacy of top-down therapy. Papers were appraised critically using the Scottish Intercollegiate Guidelines Network score to evaluate current evidence for the use of top-down therapy. Nineteen studies were identified, including six randomized controlled trials, thirteen cohort studies, and two cost-benefit studies. Early combined therapy involving both biologics and immunomodulators was found to be effective at improving patient outcomes; however, early biologics alone were not shown to have a clear benefit over step-up therapy. Likewise, the early use of immunomodulators alone showed inconsistent results with respect to efficacy in terms of both remission and surgical outcomes. Evidence for application in pediatric populations was also inconclusive. The cost-benefit analyses found that top-down therapy merits investigation, as it proved to be economical given current data. Top-down therapy has the potential of being a viable alternative to step-up therapy, but further studies are needed to determine the most appropriate patients to receive this treatment.

Keywords: Crohn’s disease; medical treatment; step-up therapy; top-down therapy.

Figure 1

Therapeutic pyramid (Figure adapted from diagram created by Aloi et al [50]) IFX, infliximab; ADA, adalimumab; CP, certolizumab pegol; AZA, azathioprine; 6-MP, 6-mercaptopurine; 5-ASA, 5-aminosalicylic acid.

Figure 2

Flowchart of review process