Clinical Experience With Biosimilars

Peter L. Salgo, MD: Let’s go on with this discussion and talk about evidence, because everybody wants evidence. We like evidence. Evidence is good. Why don’t you start us off by telling us what your clinical experience has been, Gary, with biosimilars? How comfortable are you prescribing the biosimilars?

Gary R. Lichtenstein, MD: It might be better to ask someone else, Peter, because in our health system, as of yet, we haven’t had the opportunity. There’s been a cost differential, and it’s actually higher to use a biosimilar than the originator.

Peter L. Salgo, MD: I’m sorry, can we just stop for a moment? It’s more expensive to use the biosimilar where you come from?

Gary R. Lichtenstein, MD: We’re an educational health system that has a large indigent population, so we get deep discounts with the use of medications and in pricing. Perhaps others would like to comment on this more from an economic standpoint? I’m not an economically focused individual when it comes to the clinical practice. It’s more based on our health system’s deals, if you would, that they’ve made with various corporations.

Allan Gibofsky, MD: At the end of the day, what we’ve heard is that biosimilars were authorized to decrease the cost of drugs and, in doing so, increase access. Now, decreasing cost is related to how well the biosimilar manufacturer can negotiate versus how well the bio-originator manufacturer can negotiate. You can anticipate that you’re not going to see the bio-originator manufacturer stand still while someone else comes in and tries to eat their lunch. So, I’m not surprised to hear that there may be systems in which the bio-originator is priced even lower than the biosimilar, which was promised to be the reduced price.

Gary R. Lichtenstein, MD: One thing I would add is that there’s a portfolio of products that various corporations may have, and there may be discounts for use of the various products that this particular corporation has. And that’s, perhaps, what’s operating.

Vibeke Strand, MD: And we have no way of knowing what those discounts are. But if there is competition, then we can see what might happen based on what happened, for instance, in Norway, where the biosimilar Inflectra was deeply discounted to a 69% discount off the price. And that was because there was a competition every year around the price.

Allan Gibofsky, MD: But that’s a single tender. A single system with a single tender.

Vibeke Strand, MD: That’s a single tender system. We don’t have that here. And since we have pharmacy benefit managers who decide and, also, this discounting with portfolios that we’re not aware of, it’s very hard for us to know what’s going to be cheaper or by how much.

Peter L. Salgo, MD: Let me back this up, because the import of my question—at first, at least—was clinically. You’re all using these biosimilars clinically. Have you tried them?

Vibeke Strand, MD: Most of them are tied up in the court system, so we can’t even try them.

Peter L. Salgo, MD: So you can’t?

Allan Gibofsky, MD: We’ve only recently had the first one approved at our institution, so our experience with it is limited. But as to the comfort level of using it, I can tell you that I divide patients into 3 categories. For new starts, it’s very difficult to make an argument that you wouldn’t put a patient on a biosimilar, because it is a biosimilar molecule. And then you have patients who are stable, and they achieved their stability of their disease (whatever disease we’re talking about) relatively easily. I would probably not have a great deal of difficulty switching that patient. And then you have the patients that you really struggled with, over a great deal of time, to get to the point of low disease activity and remission. Those are the patients who are referred to as the “sleeping baby.” You don’t want anything done to disturb the sleeping baby. I think I would have more difficulty switching that patient. Indeed, the patient would have more difficulty accepting a switch.

Peter L. Salgo, MD: Right. I foresee a patient going, “Whoa, whoa, whoa. We just got this fixed and you want to go fiddling with this?”

Gary R. Lichtenstein, MD: Peter, the big issue is not just 1 switch but multiple switches. You have agent X that then is started. Agent Y is given because of a deal that’s made. And then, an originator might be used. And the question is, what effect does that have? Unfortunately, we don’t have data to guide us on that.

Peter L. Salgo, MD: When we talk about evidence-based care, we need evidence.

Gary R. Lichtenstein, MD: Agreed.

Peter L. Salgo, MD: Evidence would be nice. In the meantime, what are we talking about in terms of the financial impact? There’s this NOR-SWITCH trial out there. I think you alluded to that. Tell me about that.

Cole Wilson, PharmD: The NOR-SWITCH trial was funded by the Norwegian government, and what it did is it looked to examine the effects of switching the originator, infliximab, to the biosimilar product (looking really at safety and efficacy) across 6 different inflammatory diseases. And what they found in that study was that there was noninferiority when comparing these 2 products.

So, there’s definitely some promise when we look to switching products to formulary or considering the use of biosimilars. But I think the thing that’s just as important is what it told us (which is kind of what it didn’t tell us). And that’s really around what we’ve already alluded to here with true practice. This was in a box. Now, we’re talking about what happens with a patient—again, in the acute care setting—who gets 1 product. They go to the ambulatory setting, and a payer dictates that they get a different biosimilar. So, the switching of real-world possibilities—it’s hard to extrapolate that data and put it into a US setting.

Vibeke Strand, MD: But we do have the data from the DANBIO registry, where the Danish government mandated that everyone go to the biosimilar. And so, now with that data, as well as with the NOR-SWITCH data, what we can really say is that the time to loss of effect is highly similar and that, basically, patients across these different diseases also have a similar experience. The NOR-SWITCH study was actually a time-to-treatment failure across all these different diseases, and none of them were of sufficient sample size to be looked at individually. You could only really look at the whole group.

Peter L. Salgo, MD: With these switch trials, were they using random drugs with different 4-letter suffixes, or was only 1 biosimilar compared?

Vibeke Strand, MD: Only 1 biosimilar.

Peter L. Salgo, MD: Only 1. So, that really doesn’t answer your question, which is, “I went here. I got A. I went there, and I got B. They’re all biosimilar. They should work. Where’s the evidence?”

Gary R. Lichtenstein, MD: The question that comes up is, should we use a concurrent immune modulator, as is very commonly done in the rheumatoid arthritis (RA) world to lessen immunogenicity? Immunogenicity is one of the biggest issues that we have a concern in in the gastroenterology arena, if you will.

Vibeke Strand, MD: We have it, too, in the RA arena. We actually know that it is a good idea to use background therapy, and there’s a variety of agents that you can use. Low dose is sufficient (which is one of the points), because patients don’t really take background methotrexate once they get on a biologic.

Peter L. Salgo, MD: I understand.

Allan Gibofsky, MD: But we don’t make our assessment of whether the drug is working in a given patient based on knowledge of immunogenicity. If the drug is working, it really doesn’t matter to me if they’re formulating antibodies. If the drug is not working, then it really doesn’t matter to me, either. I’m going to switch the drug. So, the rationale for the switch in the rheumatology world is less concerned about that than it is for Gary.

Vibeke Strand, MD: And on a group basis, you can say, “OK, immunogenicity is associated with loss of benefit,” and, therefore, switch. But, on an individual patient basis, that may not be true at all. There are plenty of patients with antidrug antibodies who are still responding.

Peter L. Salgo, MD: You’re the ultimate clinician in this regard. “Is this drug working for my patient? If it is, great. If not, let’s do something else.” Fair?

Allan Gibofsky, MD: Exactly right.

Gary R. Lichtenstein, MD: You have to be careful in gastroenterology, because there’s silent disease in Crohn’s, for example. You may feel great, but the disease is progressing. It’s a progressive, destructive disease that leads to fistula, strictures, and abscesses. And, if we think of that, it may be 8 to 10 years that we need to use medications to prevent disease from occurring, surgically. And that’s something that is not the same as, necessarily, other diseases.

Allan Gibofsky, MD: Well, we know that’s the case in rheumatology, as well. We know that people who are in numerical remission, by whatever standard we’re using, may still have active synovitis or active erosions going on. Our challenge becomes, how do you match someone who’s feeling good with the fact that their pathology may be advancing?

Gary R. Lichtenstein, MD: That’s why the FDA (Food and Drug Administration) has gone with originators to the PRO—the patient reported outcome—plus mucosal assessment in the IBD (inflammatory bowel disease) world. Mucosal assessment is, arguably, the most important aspect of what we do.

Peter L. Salgo, MD: And, again, if they’ve done it with the original drug, they feel the biosimilar is similar enough that they should repeat all of that. So, what does that do from managed care’s perspective? Are the European studies translatable to the United States? And if so, how and what is that going to do to the formularies?

Cole Wilson, PharmD: I think yes and no. The data is promising but, again, it’s limited in that space and in that box. It’s hard to apply it to some of the standards that we have in care in the US, so I think a lot of it is yet to be seen.

Peter L. Salgo, MD: Do you see formulary managers saying, “Look at this. There’s a cost savings here. It’s a biosimilar, and the European studies look great. Let’s take the original drug off.” Do you see that?

Cole Wilson, PharmD: No. Again, you’re talking about the waking of the sleeping baby. You have a number of patients. A lot of times, it’s about consumer choice. It’s about provider choice. We have a number of patients who are being successfully treated on a particular therapy. I think it’s unfair for us to necessarily take them away and maybe limit the success of care that they’re having. I think there’s an equal playing field for both, and there might be preferred options (just like there are in any other payer networks). But I don’t know if we can necessarily pick one and limit choice.

Peter L. Salgo, MD: I heard a word, “unfair,” from a payer. You know that that’s often the case with other disease states with other drugs. Eventually, when things get settled out, and some therapies are shown to be effective and equivalent, they go into lower cost. That’s what’s in the formulary, and then the clinicians go to war. That’s a fair statement, isn’t it?

Cole Wilson, PharmD: Sure.

Peter L. Salgo, MD: So, we’re going to have to see how that plays out.