CDDW 2016. Current and Upcoming Biologics for Treating IBD

CARE Faculty Perspective: Anti-tumor necrosis factor (TNF) agents were the first biologics used for treating IBD. Anti-TNF agents, infliximab, adalimumab, and golimumab, and vedolizumab are currently being used in clinical practice. In addition, ustekinumab is being investigated in Phase 3 clinical trials and is expected to enter the Canadian landscape shortly. What follows is an overview of each of these agents.

 

Infliximab

Infliximab is the most studied anti-TNFα agent and has been available in Canada for many years. It continues to be a safe and effective agent with benefits observed in both clinical remission and mucosal healing for patients with CD and UC (both children and adults). It is administered intravenously in a hospital or clinic, which allows for physicians to better control and ensure patient adherence.

A subsequent entry biologic (SEB) or ‘biosimilar’ to infliximab is currently being developed, and will likely enter the Canadian market shortly. It is important to be educated and aware of the differences between these agents in terms of cost (value) and manufacturing processes, and the subsequent effect these could have on the safety and efficacy of the agent. For more information on SEBs, please click here to see the needs assessment that is included with this report. 

 

Adalimumab

Adalimumab is administered subcutaneously and is able to induce and maintain remission of moderate-to-severe active IBD patients who have experienced an inadequate response to conventional therapy (ie. corticosteroids, azathioprine and/or 6-mercaptopurine (6-MP) or are intolerant to these therapies.

 

Golimumab

Golimumab was approved in 2013 for the treatment of patients with ulcerative colitis. It has shown to induce rapid and continuous clinical response to symptoms, which can help optimize patients’ quality of life. It is offered in a self-administered subcutaneous delivery form, which provides patients added convenience.

 

Vedolizumab

With vedolizumab now available in Canada for the treatment of ulcerative colitis, clinicians are wondering what the best way to optimize the efficacy of this agent. This post-hoc analysis of GEMINI I and II presented at ACG 2015 (Abstract 21, Feagan et al.) suggests that concomitant therapy with vedolizumab and immunosuppressants was no better than vedolizumab alone in maintaining efficacy. However, further prospective studies are required to better define the role of combination therapy with vedolizumab. We eagerly await more data on this exciting agent in development.

 

Ustekinumab

Data presented at ACG 2015 (Abstract 54, Feagan et al.) now supports its use in patients without prior anti-TNF failure. Although these data are very promising, there are still questions that need remain unanswered: Is it effective for maintenance therapy? What is the impact on endoscopic healing? What is the impact on fistula closure? Immunogenicity?

 

Additional CARE Considerations:
The CARE Faculty has always considered a step-wise approach for the treatment of IBD (while still considering other factors that indicate whether a patient could progress or not). It has been standard for a while and has been proven to work. For patients with mild-moderate disease, this approach generally begins with 5-ASA therapy.
5-ASAs, a highly effective, safe, and well-tolerated therapy, has been used for treating patients with mild-moderate IBD for over 30 years. Recent trials and comparative studies have led to refined treatment
strategies that optimize use of 5-ASA therapy. It is recommended to begin with lower doses. More information on 5-ASA therapy will be included in the upcoming CARE Perspectives Conference report from the European Crohn’s and Colitis Organisation (ECCO) annual meeting.
While the step-wise approach has been recognized as the standard, the introduction of biologic therapies has shifted the treatment paradigm in IBD. In 2015, a CARE publication that was developed that focused on prognostic predictors in Crohn’s Disease. This tool focused on using a personalized approach for determining which therapy a patient should be put on. For more information, click here.