Investigational agents for Crohn's disease
Mario Cottone1, Ambrogio Orlando, Sara Renna
1Department of Internal Medicine, University of Palermo, Ospedale Villa Sofia-Cervello, via trabucco 180, 90146 Palermo, Italy.
Importance Of The Field:
Increased understanding of the biological mechanisms of Crohn's disease has opened the door to a large number of new molecules; some of these are approved for clinical use, while others remain under evaluation. In this review, we examine the clinical efficacy of all the new drugs that have been evaluated in controlled trials in the last 12 years.
Areas Covered In This Review:
Anti-TNF therapy has been reviewed briefly, given the many comprehensive reviews on this topic; attention is focused mainly on the other biological therapies. In assessing the clinical efficacy of these molecules, we consider only the remission rate, as this is considered the most meaningful end point in clinical practice.
What The Reader Will Gain:
We analyzed the main biological mechanisms of Crohn's disease and the new drugs whose use is based on insights into these mechanisms. We reviewed the following new drugs: probiotics, GM-CSF, IL-10, IL-11, anti-IL-6, anti-IL-12/-23, everolimus, anti-IFN-γ, IFN-β-I, co-stimulators, anti-integrins, anti-intercellular adhesion molecule 1, small molecules and mitogen-activated protein kinase inhibitors.
Take Home Message:
Anti-TNF therapies remain the best options, followed by anti-integrin drugs. The most promising new therapies are anti-IL-23, but further data are necessary. The disappointing results with other molecules may depend on the quality of trials and possibly on inadequate dosage of the drug.
Insights
New biological therapies for Crohn's disease show promise, with anti-tumor necrosis factor (TNF) and anti-integrin drugs remaining effective. Anti-interleukin-23 (IL-23) therapies are particularly promising, though further research is needed.
Area of Science:
- Gastroenterology and immunology
- Crohn's disease pathogenesis
- Novel therapeutic targets
Background:
- Advances in understanding Crohn's disease biology have led to numerous new drug candidates.
- While some therapies are approved, many are still under clinical evaluation.
Purpose of the Study:
- To review the clinical efficacy of novel biological therapies for Crohn's disease evaluated in controlled trials over the past 12 years.
- To focus on remission rates as the primary endpoint for assessing treatment effectiveness.
Main Methods:
- Brief review of anti-tumor necrosis factor (TNF) therapies.
- In-depth analysis of other biological therapies, including probiotics, cytokines (e.g., IL-10, IL-11), and targeted agents (e.g., anti-IL-6, anti-IL-12/23, anti-integrins).
- Evaluation based on remission rates in controlled clinical trials.
Main Results:
- Analyzed various novel drugs targeting Crohn's disease mechanisms, including probiotics, GM-CSF, IL-10, IL-11, anti-IL-6, anti-IL-12/-23, everolimus, anti-IFN-γ, IFN-β-I, co-stimulators, anti-integrins, anti-ICAM-1, small molecules, and MAPK inhibitors.
- Identified anti-TNF therapies and anti-integrin drugs as current leading treatments.
- Highlighted anti-IL-23 agents as the most promising emerging therapies.
Conclusions:
- Anti-TNF therapies remain the standard of care, with anti-integrin drugs as a strong second option.
- Anti-IL-23 therapies show significant potential, but require additional supporting data.
- Suboptimal trial design or drug dosage may explain disappointing results for other investigated molecules.
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