Drs Obeidat and Okai discuss long-term data with oral DMTs that were recently presented at ACTRIMS 2022.
Ahmed Zayed Obeidat, MD, PhD: Clinical trials are a great way of learning about medications, a great way to bring medications to market, and a great way for us to understand efficacy, major safety concerns, and also tolerability of the medication. Yet clinical trials are shortly timed: 2 or 3 years. Long-term data are really important, and often, long-term data stem from clinical trial programs where you have the open-label extension and are collecting data over years. People, and even patients, ask me sometimes, “How many years has this medication been approved?” Or, “How many years do we have of data?” What really defines long term is a hard question because it 5 years long term or 10 years long term? We don’t know. What I always tell my patients is that the more years we have, the more it is long term, but 1 extra year of knowledge is important. This is something we use to help us to decide on treatments, but also to understand monitoring, needs, and efficacy data. So long-term data are of immense importance. I want to ask you to discuss some of the long-term data we have on oral medications that are approved for relapsing-remitting multiple sclerosis.
Annette Okai, MD, FAAN: This is a very important topic for patients, because like you said, they want to know how long the medication has been out and if they are going to be tested with this new therapy. My response is, before the medication comes to market, you have at least 5 years of clinical data. One thing you mentioned, Dr Obeidat, is that in the clinical trials, it only goes for a certain period of time. Is that really long term? Do we consider that long-term? What I must point out here is that, even when the clinical trial ends, there is still an extension phase in which these patients are followed, and then new studies are also opened to look at the medication in the real world, as we call it. We need to look at the medication in the real world and not a pristine clinical environment.
Speaking about some of the long-term data we have with the oral therapies, there have been several, and I will start with the fumarates. Like I mentioned before, the first one that came into the market was dimethyl fumarate, and there have been long-term data. What is encouraging with most of these long-term data, for physicians, we want to see that safety is maintained. That what we saw in the clinical trial is the same thing that we are seeing in the real world, and we are not seeing new issues pop up over time. We also want to make sure efficacy is sustained over a long period. We also want to make sure that tolerability is not an issue. Several of these medications, the fumarates, have shown that safety has been maintained over time, and in certain cases, efficacy has also been shown to be the same. There hasn’t been a big difference from what we saw in the clinical trials compared to what we see in the real world with a long-term extension follow-up, as we call it.
With the S1P [sphingosine-1-phosphate] class, we have fingolimod, which was the first one approved. Over time, the safety signals have also remained the same. We saw the same with teriflunomide. The safety signals are the same and efficacy is comparable to that of the clinical trials. The newer one to oral therapy is cladribine. Cladribine was recently approved, but I’d like to say that the trials were done a long time ago. So, even though it’s 2 or 3 years on the market, we have data up to 9 years that show there have not been any new safety signals. The efficacy data we saw in 2009 are the same as we are seeing now. Patients respond to these medications over time, and this has remained the same. So, I think when it comes to long-term data and how we see them in the real world, it’s important to look at the studies. We need to look at extension data and what we can get from real-world experience by looking at databases from various places to draw a conclusion on the safety, tolerability, and efficacy of these medications.
Ahmed Zayed Obeidat, MD, PhD: This is a great summary of real-word data, and also long-term data. You mentioned cladribine studies were done earlier, with short dosing and then treatment-free periods, but showed sustained efficacy. It’s interesting to talk about these medications.
Transcript Edited for Clarity