PF-00547659 for the treatment of Crohn's disease and ulcerative colitis.

Abstract

INTRODUCTION:

Gut-specific homing is mainly mediated by the expression of MAdCAM-1 on endothelial cells. An increase in MAdCAM-1 expression has been shown in patients with inflammatory bowel disease (IBD). Areas covered: PF-00547659 is a fully human monoclonal antibody (mAb) toward MAdCAM-1 on endothelial cells, blocking its binding with the α4β7 integrin on leukocytes. This review discusses the available data on effectiveness and safety of PF-00547659 in IBD. Expert opinion: A phase II study in moderate-to-severe ulcerative colitis (UC) patients, both naïve and previously exposed to anti-tumor necrosis factors, showed that PF-00547659 was superior to placebo for induction of remission, response, and mucosal healing at week 12. In contrast, preliminary results in a similar study in Crohn's disease (CD) did not show a superiority of PF-00547659, suggesting that PF-00547659 may have limited impact over CD outcomes. However, the time frame needed to evaluate clinical effectiveness of PF-00547659 may be longer in CD patients, given its transmural characteristic. In addition, it should be taken into consideration the possibility of incorporating new tools and more objective parameters in disease assessment that are proven to better correlate with inflammation. Future randomized-controlled trials are needed to confirm the efficacy of PF-00547659 in CD.

• Authors: Mariangela Allocca, Daniela Gilardi, Gionata Fiorino, Federica Furfaro, Marjorie Argollo, Laurent Peyrin-Biroulet, Silvio Danese
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 27 Issue 7 Pg. 623-629 (Jul 2018) ISSN: 1744-7658 [Electronic] England
• PMID: 29985060 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal, Humanized
• Cell Adhesion Molecules
• Gastrointestinal Agents
• Immunoglobulins
• Integrins
• MADCAM1 protein, human
• Mucoproteins
• integrin alpha4beta7
• ontamalimab

Topics

• Antibodies, Monoclonal, Humanized (adverse effects, pharmacology)
• Cell Adhesion Molecules
• Colitis, Ulcerative (drug therapy, genetics, physiopathology)
• Crohn Disease (drug therapy, genetics, physiopathology)
• Gastrointestinal Agents (adverse effects, pharmacology)
• Humans
• Immunoglobulins (genetics)
• Integrins (metabolism)
• Mucoproteins (genetics)
• Severity of Illness Index
• Time Factors
• Treatment Outcome