Question and Answer

Moderator: Good afternoon and thank you for joining us for today's teleconference. My name is Jessica Brown. I am with Princeton Media Associates, and I will be your moderator for today's Q&A session. Joining us today are Dr. Jonathan Leighton, Dr. Randolph Fugit, and Dr. Sharon Dudley-Brown.

Dr. Leighton, do you have any opening remarks?

Dr. Jonathon Leighton: I would like to welcome the participants, and I hope they all found the presentations useful. I think one of the main points that I tried to make in the presentation was that Crohn's disease is, indeed, a chronic disease associated with a lot of morbidity and mortality. For that reason, it is critical that we use the correct medications for our patients with Crohn's disease. And for those with moderate-to-severe disease, I think it is important that we use immunomodulator or biologic therapy to maintain remission and alter the natural history of the disease. Thank you.

Moderator: Thank you, Dr. Leighton. Dr. Fugit, do you have any opening comments?

Dr. Randolph Fugit: Once again I want to thank everybody, and also to echo Dr. Leighton’s comments, we really appreciate you taking the time out of your day to listen to our discussion today. And basically to paraphrase some of the eloquent ideas that Dr. Leighton has described in his program, this is a very important time for those of us who manage this very significant disease state; that we actually can hopefully alter the natural history, if you will, of this disease state. In the past year, we have had 3 new agents added to infliximab that may offer additional benefit to our patients, especially in the ability to maintain remission of this very substantial disease state.

Moderator: Thank you, Dr. Fugit. Dr. Dudley-Brown, do you have any opening remarks?

Dr. Sharon Dudley-Brown: Again, I echo the sentiments of my colleagues, Dr. Leighton and Dr. Fugit, and I want to thank them for a great presentation covering everything you need to know about Crohn's disease and the issues that are happening in terms of the importance of adherence. And I think that is the important message—that patients know that there are multiple therapies now for the management of Crohn's disease and that we can help them make decisions about choices for managing their Crohn's disease, because their ability to agree with a choice of treatment is important in terms of maintaining that medical regimen even while they are possibly in remission, as Dr. Leighton stated. So, thank you.

Moderator: Thank you. Our first question comes from the line of Jeremy Funkhouser. Please go ahead with your question.

Participant: Thanks for the presentation everyone. I actually had a question with the advent of top-down therapy. I know we are going to be using these higher-priced biologics earlier and earlier in the course of this disease. Are you aware of any pharmacoeconomic studies or have they evaluated that in any way?

Moderator: Dr. Leighton, do you have any thoughts on this topic?

Dr. Leighton: That is an excellent question. We know that the biologic therapies work and we know that they work in patients who are otherwise refractory to other medications; but, we also know that they are expensive. There have been several outcome studies and, in fact I shared a couple there, which do suggest that the biologic therapies do reduce hospitalizations and do reduce surgeries, and therefore alter the natural history of the disease. And if you look at some of the economic studies that have been done, which I did not specifically show, then it does suggest that they are cost-effective in the long term. But, of course, I think we also need additional studies to confirm that. And, I would be curious what Dr. Fugit thinks about that.

Dr. Fugit: Absolutely, I concur completely. As you had mentioned, you had referred to the Oldenburg and the Lichtenstein data, regarding this issue. And, unfortunately, from a pharmacy viewpoint, drug costs are going to increase dramatically versus the alternative agents that we now have available to us.

So from a silo perspective, drug costs for the pharmacy do go up. However, if we look at this from a hospital-wide policy—and alluding to the similar studies that Dr. Leighton just discussed—we have seen that a greater percentage of patients do achieve remission. A greater percent of these patients are going to use less healthcare dollars, as defined in at least 2 of the pharmacoeconomic studies that I have reviewed have suggested a substantial reduction in both ER visits and total overall healthcare cost utilization. And then, as Dr. Leighton mentioned most significantly in his presentation, that the vast majority if not all of these patients will require surgical intervention at some point during their disease state. Yet, these studies have actually demonstrated that there is a significant reduction in the number of surgeries, and if so, putting off the time to first surgery in these individuals. 

So, I think as Dr. Leighton said, we do need long-term studies—probably greater than 20 to 30 years out—to be able to demonstrate a substantial pharmacoeconomic benefit from any of these agents; by that time, they will be generic and fairly inexpensive anyway. But with that said, at least the data that we have to this point does show that remission rates are achieved faster, they are achieved and they have a more significant or durable remission, and likely will reduce overall treatment costs.

Moderator: Thank you. Dr. Dudley-Brown, would you like to comment?

Dr. Dudley-Brown: Yes, I will keep mine brief because Dr. Leighton and Dr. Fugit have certainly answered that question. My only comment would be that there is still a little bit of a debate in terms of when to actually start biologics and is it appropriate for everybody. And I think some of the data looking at the phenotype of the severely ill Crohn's patient and the fistulizing patient—that data certainly suggests that those are definitely the patients that need to be started very quickly on the biologics. 

Moderator: Thank you. Our next question comes from the line of Dannette Musil. Please go ahead with your question.

Participant: Thank you. I just wondered what you consider an adequate trial for the biologics before you determine whether you have efficacy?

Moderator: Dr. Leighton, do you have any thoughts on this topic?

Dr. Leighton: Thank you. That is also another great, great question. I think that most of the studies show that you will see responses out to the third dose, for example, of infliximab. So, in the case of infliximab—which is given as a loading dose at 0, 2, and 6 weeks—most people respond at 2 weeks and 4 weeks, but you still can see people respond at 6 weeks. So, I will oftentimes give patients 3 loading doses, and if I do not see any response, then I would not go any further. There is less data on adalimumab and certolizumab pegol, but I use that same approach where I will at least go through the 3 loading doses for adalimumab 160 mg, 80 mg, and then 40 mg; and then the certolizumab at 0, 2, and 4 weeks. And, I think that if at the end of those dose times you do not see a response, then there is not much reason for continuing the medications beyond that point.

For the immunomodulators, it is a little different because with 6-MP you can see responses out as far as 3 to 6 months. So, a lot of times I will continue those drugs for a longer period of time. Thank you.

Moderator: Thank you. Dr. Fugit, would you like to comment?

Dr. Fugit: I concur completely with Dr. Leighton’s response that he has discussed on these issues. And as we know, the majority of data on the biologics is with infliximab at this point, and most of you are well aware what the package insert states—that patients who do not respond by the fourteenth week of therapy are unlikely to respond with any continued administration. With that said, one of the big issues that has been brought up recently with the use of infliximab is the development of antibodies that can lead to infusion-related reactions. But, also quite possible is that we may have patients who are not responding as significantly as they did early on in therapy. So, with that said, a patient who has not responded by the fourteenth week of therapy, there pretty much is no additional benefit with the use of this agent. However, as Dr. Leighton described in some of the trials, that does not mean you are out of the game now. Whether it is with an additional anti-TNF agent and we have the possibility of natalizumab now—which is an entirely different class of agent, being a selected adhesion molecule inhibitor—that may be able to affect these patients from a different side, if you will, or different mechanism of action.

I can concur completely with his use of the immunomodulators, as well. 

Dr. Leighton: If you do not mind, I would just like to add to that that there are data to show that if you do not respond to one anti-TNF, then as we mentioned, you may respond to a second. And at our big GI meeting, DDW, this year there is even an abstract to show that you can get a clinical response to a third anti-TNF. So, you do have leeway if you do not respond to the initial one that you use.

Moderator: Thank you. Dr. Dudley-Brown, would you like to comment?

Dr. Dudley-Brown: Sure, thank you. It is a great question. And the notion of what is an adequate trial is a question that continues to be debated because the issue is how people are defining response. And if you look at the data that has been generated by all of the studies across these 4 agents that we have been discussing, they measure mucosal healing differently; they measure symptom response differently; and some is physician-driven decision-making. That is what makes it very difficult to get a grip on comparing medications from one trial to another. 

Moderator: Thank you. That was our final question for today.