Madelaine Feldman, MD: We trust the FDA to make the right decision. When the [approval of the] first biosimilar for adalimumab came out, I was at that FDA meeting and spoke. And there appeared to be some concern, particularly among the pediatric gastroenterologists because that particular biosimilar had never been used in that population. However, the FDA did approve it and did extrapolate to [gastrointestinal, GI] indications as well.
I think over the years, as we see the use in other disease states rather than just the one that it was studied in, and we don’t see any increase safety signals, the confidence will be there for extrapolation. Although one of the most recently approved biosimilars did not get extrapolation from oncology to rheumatology. So, it’s not a given that extrapolation will be to all disease states.
In terms of the specialties that might have the most concern, I think probably oncology, because if it doesn’t work, their patients die. GI; inflammatory bowel disease, if there’s a problem, increased hospitalizations, infections, more surgeries. So, I think depending on what the adverse event would be if there is a problem will determine which specialty will have more concern.
As a rheumatologist, our field basically surrounds immunology. And autoimmune patients have, for lack of a better word, a "finicky" immune system that can be triggered by the slightest thing. We understand now about epigenetics and how something as simple as sunlight can affect the epigenes, change the DNA methylation, and cause increased T-cell activation. So, we are always concerned about immunogenicity, and that may be one of the reasons why you’ll find more rheumatologists concerned about immunogenicity with biosimilars. Because any small changes within the immune system in our patients can cause a flare.
So, I think the patient population is going to determine whether there’s going to be more of a problem with immunogenicity. It’s kind of a code word now. Everybody’s like, “Oh, we don’t want increased immunogenicity. If we switch too many times, is there going to be immunogenicity?” And I think there, sometimes, may be a little bit an over concern. Again, an infection changes the immune system in our patients. So, I think there’s concern and I think there should be, but I think, again, real-world evidence will hopefully show us that our concerns are unfounded. One of the things that I think in terms of switching, because I think that’s where the term immunogenicity comes out a little bit more is when we switch from the reference to the biosimilar, I think what’s going to happen, again because of our drug delivery system here, I mean we could have switching between biosimilars, among 5 different biosimilars. And the phrase that I coined at that first meeting was the great American switching experiment. And that may be, but what really is and hopefully it will all work out just fine.
Rheumatologists have had to become comfortable with pharmacy benefit managers switching our patients from one medication to a completely different medication. We’re not comfortable with it but it happens. That is one thing that I think we may have a big problem with. It remains to be seen. Obviously changing from a reference product to a biosimilar is nowhere near as problematic as having the drug itself be changed to a completely different drug, maybe even a different mechanism of action. So, I think the concern won’t be as great. There are some large health systems that have been switching from the reference to the biosimilar, and I think that there is going to be some pharmacovigilance and some studies being done. And I think as that proceeds and we see no new safety signals come up, I think again that will create a little bit more confidence. The Europeans do things completely differently than how we do it here, so I’m not sure their interchangeability discussion is sort of apropos or works in the United States. We have powers that be that change our drugs as well.