Russell Cohen, MD, on Optimal Use of Anti-integrins and Anti-TNFs in IBD

Dr Cohen recaps his presentation from the Advances in Inflammatory Bowel Disease regional meeting held on August 7 on the use of anti-integrins and anti-tumor necrosis factor therapies for treating Crohn disease and ulcerative colitis.

Russell Cohen, MD, is a professor of medicine and director of the IBD Center at the University of Chicago.

TRANSCRIPT:

Dr. Russell Cohen:  Hi. I'm Dr. Russell Cohen. I'm a professor of medicine and director of the Inflammatory Bowel Disease Center here at the University of Chicago.

One of the topics that I spoke about today at the August Advances in IBD meeting was the use of anti-integrin and anti-TNF therapies in patients with inflammatory bowel disease and how to optimally adjust those therapies.

Many of you may not realize that we've had anti-integrin therapies available since the mid-2000s for Crohn's disease. The drug natalizumab, which was initially approved for multiple sclerosis, has been used for Crohn's disease, although we rarely use it today.

However, that therapy, which was given as a once-monthly infusion, was a true breakthrough for patients in whom the anti-TNF therapies didn't work or they could not tolerate.

Unlike most other therapies, there are rules when using natalizumab. One of the rules is that patients cannot be on other immune modulators at all. The second rule is that if they can't get off steroids within 6 months, you should discontinue therapy and think of something else. The third rule is that prior to starting natalizumab, you need to check patients for the JC virus.

If they are positive for JC virus, we typically do not use natalizumab. If they are not positive for the virus, we recheck it roughly every 6 to 12 months. This is because of the link to progressive multifocal leukoencephalopathy (PML). As a result, we rarely use this therapy, but it is important to know because it is very effective in patients with Crohn's disease.

The other anti-integrin therapy that's FDA-approved is approved for both ulcerative colitis and Crohn's disease. It's called vedolizumab. It came to market in 2014. One of the very nice things about vedolizumab is that it is a very safe therapy. We're not aware of any strong links to any type of cancers or infections. It is currently only available IV, but we're hoping that there'll be a subcutaneous version finally FDA approved, hopefully within the next 1 to 2 years. As a result, since it is both approved for ulcerative colitis and Crohn's disease, we find it very useful.

We typically dose it, after the initial week 0, 2, and 6 load, every 8 weeks. There is good data supporting dose escalation to every 4 weeks in patients both with Crohn's disease and with ulcerative colitis for those who have a partial response or lose response to the every-8-week dosing.

The other major category therapies are the anti-TNF agents. I'm sure many of you are familiar with them. There are currently four FDA-approved anti-TNF therapies in the United States — infliximab, adalimumab, certolizumab, and golimumab. Both infliximab and adalimumab are approved both for ulcerative colitis and Crohn's disease. Certolizumab is just approved for Crohn's disease, and golimumab is just approved for ulcerative colitis.

Many of these therapies are ones that you have to first check for TB or hepatitis before doing and dosing. Once patients are on therapy, you may need to check throughout depending upon their exposure.

One of the ways to optimize therapy with it is to increase the dose if needed, to add an immune modulator— 6-MP thiopurine, methotrexate—to boost drug levels, combat antibodies. Particularly, if patients have fistulizing Crohn's disease, you may need to do that as well too. We often don't do that in patients who failed multiple therapies.

We're hoping that a recently discovered allele genetic test can identify patients who'll make antibodies against the anti-TNF therapies. As this allele becomes more widely available -- it's now available for testing through a commercial lab -- we may do that as the first step before starting anti-TNFs in our agents.

This is Dr. Russell Cohen from the University of Chicago. Thank you for joining me today.