Dr Allegretti reviews her presentation at the Advances in Inflammatory Bowel Disease regional meeting on how to position sphingostine 1-phosphate receptor modulators to optimize patient care in IBD.

Jessica Allegretti, MD, is medical director of the Crohn's & Colitis Center at Brigham and Women's Hospital in Boston, Massachusetts.

TRANSCRIPT:

Speaker 1:

My name is Jessica Allegretti and I am the medical director of the Crohn's and Colitis Center at Brigham and Women's Hospital, and I recently presented at the AIBD Regional Conference on harnessing the utility of selective sphingosine 1-phosphate receptor modulators to optimize patient care in IBD. What we covered was that notably, advancing therapy to biologics may be challenging for some patients. Some patients may view the need to advance therapy to a SubQ or an IV biologic as a sign of worsening disease. Some patients certainly may prefer a different route of administrations. We know that some patients may have safety concerns with biologics and often patients have a reluctance that can make these conversations somewhat difficult. So enter targeted small molecules, which have a targeted mechanism of action, an oral route of administration which many patients find favorable, and very good safety characteristics.

So if we think about the S1P receptors, we know that there are S1P receptors all over your body, receptors 1 through 5. And so these agents basically bind to those receptors and sequester lymphocytes into lymph nodes. And so again, this causes this internalization of the receptor, essentially trapping lymphocytes in the lymph nodes so they can't go out into the circulation and cause inflammation. We do have several agents in this category now. Ozanimod has already been approved for the treatment of moderate to severe ulcerative colitis. And if we look at the induction data, we see 18.4% of patients receiving ozanimod achieved clinical remission compared to 6.0% in the placebo arm. Notably too, we see overall the efficacy at 52 weeks. We see a similar trend with 37.0% of the patients treated with ozanimod achieving clinical remission compared to 18.5% in the placebo arm out at week 52.

We also have etrasimod, which is currently being studied and likely will be coming to market eventually. And when we see the efficacy data at the induction time points for etrasimod, we see similar trends with that—patients treated with etrasimod had significantly higher rates of clinical remission compared to those in the placebo arm with a delta of about 21.2%. And so in summary, ozanimod is effective for induction and maintenance therapy of remission in UC with a reassuring safety profile, and I provided you with some of those numbers today—more effective for less symptomatic and less treatment-exposed patients. So we know that these therapies are often used best upfront before patients have been exposed to multiple different MOAs. There have been low rates of cardiac conduction abnormalities and macular edema. However, we do recommend that you get a baseline EKG in these patients and a baseline eye exam if patients have a history of macular edema or inflammatory eye disorders.

There is limited data on pregnancy with this class of drugs. So if you have a patient who either is pregnant or wanting to get pregnant very soon, we wouldn't recommend this class. Ozanimod really should be considered first-line treatment for patients with concurrent MS because this is also a drug that has been approved for that indication. And certainly you can consider ozanimod as a first line for patients who are bio-naive with UC, with moderate to severe symptoms with a preference for oral administration. Etrasimod, however, is also coming and is showing to be effective also for induction and maintenance therapy. And so soon we certainly may have a choice of more than one agent within this class. So thank you again so much for your attention.