Marla Dubinsky, MD: In terms of selecting from this menu of therapies that we have, I’m going to particularly focus on biologics and sort of talk about how my mind sort of wraps itself around the factors when I have a patient sitting in front of me. I’m going to start by saying that I’ve kind of developed this new strategy in which someone has to earn infliximab. Because of its weight base, because we understand the pharmacokinetics, because it’s been out for 20 years, because we have a lot of dosing flexibility, and because it sort of works quickly and we feel confident in its dosing strategies for a hospitalized ulcerative colitis patient, because of very bad ulcerative colitis or even a hospitalized Crohn patient, the IV [intravenous] administration of infliximab becomes sort of a gold standard for us. And so that’s why I say you have to earn it. Or if you have really severe perianal disease, that’s the best drug we have. For disease that’s very extensive in the small bowel, you want to have as much flexibility and dosing as possible. The difference between some of the self-injectables and the IVs is that the IV, particularly infliximab, is dosed based on weight. So that’s why we feel a little bit more confident in that.
I think patient preference comes into play. A patient may say “I don’t like to inject myself” or “I’m nervous” or “I have fear or anxiety around injectables. I feel more confident with IV.” Or now that we have an oral molecule in ulcerative colitis, we know that convenience is probably No 1 for our patient. However, safety does come into play. But what I tell patients is, “The most important thing is treating your disease.”
And then I’m saying, “What are the risk factors that help me think I would use one therapy over the other?” We think about efficacy. They got approved so we assume that their efficacious, but there is a hierarchy, and that’s why I noted that you have to earn infliximab. Also, if a patient is traveling or is going to school and doesn’t have access to an infusion center, obviously subcutaneous and oral make more sense. I think that disease severity drives my choice. And then I consider the patient and convenience. Obviously, safety is very important. But as I noted, the biggest safety issue with these medicines is the disease—meaning not effective for the disease and the disease worsening.
So there are segments of patients for whom I would use one option over the other. For example, in an older population or advancing age population, I have to consider the safety of vedolizumab. This is gut directed. This is not systemic sensitive. It’s not used for psoriasis or rheumatoid arthritis. It’s specific for the gut. The safety profile is very nice. And so for patients who are at risk of malignancies or serious infections, as you age that becomes a thing. Then we would maybe use vedolizumab.
If you had to ask me what my choices are, I think about so many variables. Lifestyle is one and age is another. I also think about family history or personal history, and malignancy, risk of immunosuppression, and patient preference. A lot of patients want to know how long a drug has been on the market. This does influence their confidence and the safety.
Obviously, safety is paramount to a patient. Patients would rather have pain or diarrhea and not have the risk of malignancy. I understand that. We have to put risk into perspective. And if a patient has risk factors for very complicated or progressive disease, we need to explain that and bring out this therapy. The biggest risk is disease progression to complications.