Oral, Small Molecule Agents for Ulcerative Colitis
What to know in terms of integrating new oral, small molecule targeted drugs into treatment plans for patients with ulcerative colitis.
Joseph Feuerstein, MD: Dr Sands, could you review our 2 newest agents, the JAK inhibitor tofacitinib and the S1P [sphingosine-1-phosphate] receptor modulator ozanimod?
Bruce E. Sands, MD: Sure. Both tofacitinib and ozanimod, in contrast with what Dr Ungaro and Dr Hanauer have been talking about, are oral agents. They’re small molecule agents. At this point, they’re approved for only ulcerative colitis within the realm of IBD [inflammatory bowel disease]. Tofacitinib is a Janus kinase inhibitor, or a JAK inhibitor. It’s a pan-JAK inhibitor. It works by basically inhibiting downstream inflammatory responses within inflammatory cells. It’s an orally available agent, and it’s effective in ulcerative colitis. But it’s positioned in its use after patients have failed anti-TNF [tumor necrosis factor] agents, so it’s a second-line agent.
Furthermore, it has recently had the addition of black box warnings for venous thromboembolism and increase in mortality. This comes from data out of the rheumatoid arthritis population, but has been generalized to its application with ulcerative colitis as well. It’s an effective agent. As with all agents, it’s somewhat less effective after patients have already failed an anti-TNF, which paradoxically is exactly the patient we would use it for.
Ozanimod is the newest one. It had already been on the market for treatment of multiple sclerosis. It works mechanistically in a different way. It’s an S1P receptor agonist, or sphingosine-1-phosphate receptor agonist. Without going into great detail about what it does or how it does it, it basically sequesters lymphocytes in lymph nodes and keeps them trapped in the lymph nodes and out of circulation. In a way, it’s another approach of targeting the trafficking of inflammatory cells and lymphocytes into the gut mucosa. But here it’s just trapping them in the lymph nodes and not killing them. Consequently, you can expect to see lymphopenia. But interestingly, you don’t see very much increased risk of infections. You see a slight uptick in herpes zoster, but not much else of note.
There are some other safety issues with ozanimod. It’s given in uptitrated dosing because it has cardiac conduction effects, which are easily titratable. You see rapid tachyphylaxis to that effect. But you want to use it with caution in patients who have cardiac conduction abnormalities. There are also rare cases of liver function abnormalities. I mentioned the lymphopenia. It can also cause macular edema—you don’t want patients who are susceptible to that to get it—and rare cases of pulmonary function abnormalities. You don’t necessarily have to monitor for that, but just be aware of that. But it’s effective in ulcerative colitis and provides another oral option for treatment.
Transcript edited for clarity.
