Importance of Efficacy and Safety Data in Ulcerative Colitis Management

Maia Kayal, MD: When starting any new therapy, it’s always important to ask yourself, how much risk am I willing to assume to balance with the efficacy of the drug? This is often an informed decision-making conversation we have with patients where we lay out the risks, the safety profiles of the medications, and the long-term efficacy. For each patient, the answer will be different because each patient is willing to assume a different risk. With the anti-TNF [tumor necrosis factor] therapies, the risk that often comes up is the long-term risk of lymphoma, which is about 0.06%. Patients are often worried about this, but without a family history or a personal history of lymphoma, and in the absence of the addition of a thiopurine agent, that risk stays baseline at about 0.06%.

David P. Hudesman, MD: What therapy should you start first? First you must look at efficacy, because whether you’re talking about safety, mode of administration, onset of action, if the drug is not going to work, all of that is irrelevant. First we are looking at efficacy, and this is when disease severity is important. For somebody with more moderate disease, probably the majority of our agents, our biologics and small molecules, will work. In more severe cases, in patients with extraintestinal manifestations, joint manifestations, skin manifestations, that’s when we’re going to want to use less selective therapies, or our anti-TNFs and our JAK inhibitors. After that efficacy mark, then you’re looking at safety and comfort, how comfortable both the provider and the patients are. What’s the disease burden, as we discussed? How quickly do we want these therapies to start working? What is the patient’s lifestyle? What’s the mode of administration? Is this somebody who’s traveling across the country, from out of the country, where an oral therapy is going to be a lot better than an infusion or an injection? Or is this somebody who has a fear of needles and needs to come in for infusion therapy? Putting that all together helps us sequence our therapies.

Maia Kayal, MD: With the anti-TNF agents, adalimumab and infliximab, there are long-term signals for an increased risk of lymphoma. This risk, however, is only about 0.06%. When we monitor our patients with infusion laboratory tests, we are monitoring their blood counts and watching for any potential change in white count, hemoglobin, or platelet count that could portend the risk of lymphoma. With medications such as ozanimod, there is a risk of bradycardia and macular edema. Before starting ozanimod, we obtain an EKG [electrocardiogram] and an ophthalmologic assessment in certain patients who might be at risk for macular edema, such as those with diabetes. In medications such as tofacitinib or upadacitinib, the significant risk is herpes zoster. Otherwise, the medications have been shown to have a safety profile that is equivalent to other biologics. In terms of ustekinumab, the safety profile across indications and across multiple studies has been shown to be equivalent to placebo; that is very reassuring. When considering safety across all the biologics and the small molecules, we tend to think that vedolizumab and ustekinumab are the safest drugs we have on the market for patients with moderate to severe ulcerative colitis.

Transcript Edited for Clarity