Developments in liposomal gene delivery systems

ABSTRACT

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Currently approved therapies include prednisone, TNF antagonists and anti-metabolites which often are ineffective and have frequent adverse effects. Consequently, UC patients are always at risk for developing serious complications that affect their quality of life. Therefore, new treatment options are required.

Areas covered: This article discusses etrolizumab, its mechanism and the potential role it can have in the future of treating UC. Etrolizumab is a humanized monoclonal antibody that selectively blocks lymphocyte trafficking and retention in the gut. The safety and efficacy data was reviewed from all randomized placebo-controlled trials which evaluated etrolizumab for the treatment of UC.

Expert opinion: Etrolizumab is an effective and well-tolerated drug for the treatment of UC. It appears to be a promising molecule that can benefit UC patients.     

Vedolizumab and etrolizumab for ulcerative colitis: twins or simple cousins?

ABSTRACT

Introduction: Vedolizumab is a monoclonal antibody that selectively blocks α4β7 integrin and has already been approved for use in patients with moderate-to-severe ulcerative colitis both as first and second line. Etrolizumab is a monoclonal antibody still being tested, which acts with a dual mechanism by selectively inhibiting both α4β7 and αEβ7 integrins.

Areas covered: This review provides an overview of the literature data of vedolizumab and etrolizumab, in order to define their role in the treatment of patients with moderate-to-severe ulcerative colitis.

Expert opinion: Etrolizumab and vedolizumab block the α4β7 integrin with a similar action mechanism. However, the inhibition of αEβ7 integrin by etrolizumab distinguishes the two anti-integrins making them ‘cousin’ drugs. Phase 3 clinical trials are needed to confirm the promising etrolizumab’s efficacy data and to resolve any doubts about its safety, allowing a clearer comparison with vedolizumab.     

Integrin antagonists as potential therapeutic options for the treatment of Crohn’s disease

Introduction: Anti-integrin therapy for the treatment of patients with Crohn’s disease is rapidly evolving. Two agents, natalizumab and vedolizumab, are approved by the United States Food and Drug Administration for the treatment of Crohn’s disease, with vedolizumab the primary anti-integrin used due to a more favorable safety profile. Several other anti-integrins are in various stages of development.

Areas Covered: This review discusses the current state of anti-integrin therapy as well as suggestions for positioning of these agents in clinical practice. Emerging anti-integrin therapies, their underlying mechanisms of action, and available safety and clinical data are also reviewed.

Expert Opinion: Anti-integrins are effective for the treatment of Crohn’s disease, even in patients refractory to other therapies. Their use should be considered in patients with Crohn’s disease who do not respond to, develop non-response to, or have contraindications to anti-TNF therapy. Anti-integrin therapies can be offered as a first biologic therapy, in particular for older patients, patients with concurrent multiple sclerosis (natalizumab only), and in patients with contraindications to anti-TNF therapy. In patients with more severe symptoms, providers should consider co-induction with corticosteroids if possible to hasten remission.