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.

Running Behind “POPO”—Impact of Predictors of Poor Outcome for Treatment Stratification in Pediatric Crohn's Disease

“…With almost 54% of patients suffering extensive disease (POPO3-positive) our findings are in keeping with own previous reports (3) and data from the EUROKIDS-Registry (17,18), showing the majority of paediatric CD patients to have pancolonic involvement. However, POPO3-, as well as POPO2positivity, were recorded significantly more often in children between 1 and 6 years of age than in older children, thus serving as further risk predictors in addition to their classification as high-risk patients based on young age (19).…”

“…4.3% of the cohort studied had stricturing or penetrating disease (POPO-6-positive), in contrast to reports from France and Scotland, with 29 and 9% of patients showing B2/B3 behaviour at diagnosis, resp., (18,28) and even higher rates in the Swiss IBD Cohort Study Group (29). These data reflect disease complications over time rather than at diagnosis.…”

Beneficial Effects of Oat Beta-Glucan Dietary Supplementation in Colitis Depend on Its Molecular Weight

“…A new top–down approach to therapy inverts this procedure and presupposes the initiation of the administration of biological or immunomodulatory medications immediately after the diagnosis of the disease to prevent later complications. Preliminary data partially confirm the validity of this concept, but its introduction for everyday practice should be preceded by clinical trials [6]. It seems likely that the development and availability of biological drugs and other new substances will improve the results of treatment of IBD in the coming years for more personalized and targeted treatment.…”

Enteral Nutrition in Adult Crohn’s Disease: Toward a Paradigm Shift

“…In the last two decades many drugs have been developed to treat CD and a ‘top-down’ approach is now favoured to achieve sustained clinical remission and resection-free survival for patients with CD [8]. Many patients do not respond to currently available treatments (immunosuppressants, biologics, and corticosteroids) or have an initial response that is not sustained.…”