Fred Lublin, MD: Let’s take a look at the individual lesion. We’ll start with interferon since that was our first agent. Sven, tell us a little bit about the use of interferon, both historically and where it plays a role now.
Sven Meuth, MD, PhD: It was heavily used 20 years ago when it was coming to the market, and the majority of patients in Germany were treated with the different interferon-beta preparations over years. However, since the approval of the oral agents, EMF [electromagnetic fields], and teriflunomide, we don’t find too many patients starting with interferons anymore. There’s a significant decrease in the usage of interferons. However, especially patients being stable over years on interferons, they like to continue therapy with these injectables, and so, never change a winning team. Interferon patients who are stable on treatment continue this treatment. However, for newly diagnosed patients, they are looking, at least in our country, more for the oral agents, so there is a development in this injectable market, I have to say.
Fred Lublin, MD: Any thoughts on the mechanism of action?
Sven Meuth, MD, PhD: This is quite a good question, and I think we can spend the next 30 minutes talking about the mechanism of agents. For our patients we try to keep it simple, and we are talking about a shift from TH1 [type 1 helper T cells] responses toward TH2 [type 2 helper T cells] responses, but I think we all know that there are many effects contributing to the mechanism of action of interferons. If we have the pathophysiology of MS [multiple sclerosis] in mind, we can nearly say that each and every step in this whole cascade is somehow impacted by interferon. It alters the cellular recognition by a modulation of MHC2 [major histocompatibility complex class 2] and the T-cell receptor. It reduces, thereby, lymphocyte activation and proliferation, but it has also an impact on the transmigration over the blood-brain barrier from the periphery to the central nervous system [CNS]. There are some data published that also in the CNS, this leads to a downregulation of pro-inflammatory cytokines, and it shifts somehow the differentiation also in the CNS toward the TH2 answer, so a very broad mechanism of action.
Fred Lublin, MD: It’s not entirely clear which one is the primary player, if there is a primary mechanism involved. Wallace, use of interferon in the United Kingdom?
Wallace Brownlee, MBChB, PhD, FRACP: Like in other countries, our use of interferon as a first-line or first DMT [disease-modifying therapy] for people with MS is definitely on the downward slope. One new thing in the last year would be the change in the label for pregnancy in Europe. We now have the option of treating women who are wanting to fall pregnant, or during pregnancy and breastfeeding, and that is on the basis of observational studies suggesting this approach is safe. There is also still a role for interferons and other injectable therapies in patients with certain comorbidities that make other treatments difficult. I recently saw a patient who’d had a renal transplant, so they were immunosuppressed on 2 immunosuppressive medications and low dose steroids, and they developed relapsing-remitting multiple sclerosis on top of that. One of the injectable agents, the patient in this case went for interferon, is a good option because you don’t need to worry about drug interactions or immunosuppressive effects.
Fred Lublin, MD: Patricia, use of interferon?
Patricia K. Coyle, MD: With regard to interferon-beta, usage is absolutely dropping in the United States, but I agree with Sven: for patients who are on it, who are doing very well, who are very happy with it, not having any significant adverse effects, there would certainly be no reason to change that.
Fred Lublin, MD: We’ve had the same experience. I haven’t started many patients with interferon, but I have individuals who I’ve been treating since November of 1993 when we first got interferon beta-1b, and they’ve done spectacularly well. As we know with all of these agents, there are some people who have responded to all of them, and I think we don’t change a winning team was much the logic. They may say, “Well, I’m not that happy about these injections, but I don’t want to change because I’ve done so well over the years.” I must say, going back to 1993, that was one of the most exciting periods of my professional life, when we had our first therapy come along for a disease, so it was really a very exciting time.
The other issue with interferon right here and now is when I’ve gotten phone calls from patients, as we all have, saying, “What about this COVID-19?” The ones who are calling on interferon, I say, “You’re in a great position because, not only doesn’t it immunosuppress you, but interferon is probably the main immune response that helps you to fight off viral infections, so we’re happy to have you on interferon.” There will continue to be a use for it in individuals, and then we’ll come back to the comorbidity issue after we have a discussion about glatiramer acetate.