Investigational agents for Crohn's disease.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Cottone
Mario
M
Department of Internal Medicine, University of Palermo, Ospedale Villa Sofia-Cervello, via trabucco 180, 90146 Palermo, Italy.
Orlando
Ambrogio
A
Renna
Sara
S
D056704:Adaptive Immunity; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000502:physiology; D003424:Crohn Disease / Q000188:drug therapy*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D015507:Drugs, Investigational / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000627:therapeutic use; D007167:Immunotherapy; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D016032:Randomized Controlled Trials as Topic; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors*; D012074:Remission Induction
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016207:Cytokines; D015507:Drugs, Investigational; D005765:Gastrointestinal Agents; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D020929:Mitogen-Activated Protein Kinase Kinases