Real-World Persistence and Adherence of Ofatumumab Versus Platform Self-Injectable Disease-Modifying Therapies in Patients With Multiple Sclerosis

Jason Freeman, MD, MBA: Welcome to CMSC 2023. I'm your host Dr Jason Freeman, Medical Director, Novartis Medical Affairs, providing you with updates from CMSC 2023. The information herein is provided for disease educational purposes only, and is not intended to be, nor does it imply medical or diagnostic advice.

Jason Freeman, MD, MBA: Joining me today is Dr Brandon Brown, Medical Director with Novartis Pharmaceuticals. Dr Brown, welcome to the program.

Brandon Brown, PharmD: Thanks Jason. Glad to be here.

Jason Freeman, MD, MBA: We're going to discuss a poster, also from Novartis, entitled “Real World Persistence and Adherence of Ofatumumab versus Platform Self-Injectable Disease-Modifying Therapies in Patients with Multiple Sclerosis.”

Jason Freeman, MD, MBA: So, Dr Brown, I want to start with a more general question about why it's important to study persistence and adherence to MS DMTs [disease modifying therapies] in the real-world setting?

Brandon Brown, PharmD: Sure. It's an important topic because, of course, as with any medication, if you don't take the medication, of course it doesn't work. It's very important to make sure that these patients are taking these medications, and when I think about multiple sclerosis as a disease state and these medications that we use to treat MS, they don't often make patients feel better, if you will, they often will slow the disease down, but patients sometimes won't feel different on the medication. That's why it's important to remind patients to stick with it and take their medications. As newer therapies come on the market and they're given in different routes, patients have different preferences now, and they have different options for which way they want to take a medication, which hopefully will increase their chances of staying on the medication for longer periods of time.

Jason Freeman, MD, MBA: And just maybe to help the audience a little bit, can you describe a little bit more by what you mean, in terms of persistence versus adherence? Just how those things are defined?

Brandon Brown, PharmD: Sure, yeah. Those are 2 terms that we often use when describing if a patient is taking the medication as prescribed. So, adherence is really if a patient is taking it exactly as prescribed. So, if the medication is prescribed to be taken once a day, they are adherent if they take it by the route of administration that is approved for that therapy, and if- that they actually take it once per day without missing doses. Persistence, on the other hand, is really how long they stay on the medication. This is really whether or not they are discontinuing due to adverse events or other issues. So those are the 2 definitions that we use when thinking about whether or not a patient is tolerating medication.

Jason Freeman, MD, MBA: Can you talk to us now a little bit about the methodology of this particular study? How was the data collected?

Brandon Brown, PharmD: Sure, yeah. So, this particular study that we are discussing was a comparison between ofatumumab therapy and the historic- the platform injectables, as we refer to them. And this study looked at claims data, so taking pharmacy and medical claims data, we're able to see how many times a patient fills their prescription, when they stop filling that prescription, and using these specific calculations, we can actually determine with reasonable certainty that a patient is taking their medication, as well as staying on their medication over time. Now, of course, there are some limitations, and we can talk about those later. We don't- we are not in the patient's home. We don't know that the patient's actually injecting or swallowing the medication, but we can make reasonable assumptions between the 2 groups when it comes to that.

Jason Freeman, MD, MBA: And I understand this was done retrospectively, or retrospective cohort, looking both at medical and pharmacy claims. So even though we can't be in their homes, I guess we can be relatively assured that the data is accurate. Does that sound about right?

Brandon Brown, PharmD: Yeah, I would say so. Again, it's certainly possible that patients are having their prescriptions filled and then the prescription just sits around. But you'd like to think that if that happens for 1 therapy, it's probably happening for another therapy, and that those effects would wash out. So, a comparison between 2 therapies should be pretty accurate.

Jason Freeman, MD, MBA: So, Dr Brown, can you help us summarize the results of these findings, both with respect to persistence and adherence?

Brandon Brown, PharmD: Sure. So, this study was designed to look at persistence at a few different time points throughout the study. So, we looked at 6 months, 9 months, and 12 months. And what we found was impressive, at 12 months 75% of the patients were still persistent on ofatumumab compared to around 43% of those on the self-injectable. So, this was a large increase over a 70% increase in the number of patients or the percentage of patients that were still persistent at the end of 12 months. So, very profound effect. And remember, we had very good effects on the primary annual, primary end point in the clinical trials, which was annualized relapse rates. So, for ofatumumab, it was about 0.1 and 0.11 in each of the trials compared to about 0.22 and 0.25, for the comparator arm, which was not an injectable, but an oral therapy. So, to get these strong benefits of reducing annualized relapse rates, you have to stay persistent on the drug. In terms of adherence, the way in which adherence is defined and was defined in this study is percentage of days covered. If the percentage of days covered is greater than 0.8 or 80%, then the patient is considered to be adherent. And what we saw in this study is that, again, a very large 73% of the patients on ofatumumab were adherent compared to only 52% of the patients on the injectables. So, very impressive results when comparing to the older platform injectable therapies.

Jason Freeman, MD, MBA: Any other takeaways from this study and how we can apply it to real-world settings? I think about sometimes the debate between route of administration, a pill versus injectable therapy. A lot of clinicians out there believe that sometimes if you give a patient an injection, they're not likely to take it, or if I bring them in and give them an infusion, we can almost guarantee that they're going to get it. So why does this study matter out there in that real-world setting?

Brandon Brown, PharmD: Yeah. No, you're exactly right. We continue to hear this over and over again, that prescribers often will prefer the infusible medication because they know that the patient's getting the drug. And I do strongly believe that they are recalling back to the days of the old injectables, where patients often would tell you they're injecting, but they're really, truly not injecting. I think it really speaks to the tolerability of ofatumumab.

Jason Freeman, MD, MBA: And are there any particular limitations on this particular study and the data therein?

Brandon Brown, PharmD: Yeah, sure. So, these types of studies are riddled with, of course, limitations. So being claims data we, as I stated before, we can't be in the patient's home, we don't know that the patient is actually injecting themselves. Also, there's a natural selection bias. So, the design of these studies obviously requires patients be on or be enrolled within the insurance plan for a certain amount of time. So that if they're not enrolled in that plan, then they're not counted in the data. So that does have some effects on the outcomes as well. We obviously can't compare between therapies. So, you mentioned the infusibles before. We would love to say, look at our persistence compared to what they've seen with other infusible medications, but we did not compare to those, so we can't really comment on that. Also, we can't guarantee that patients are taking their medication exactly as prescribed. So even though it's prescribed once monthly, perhaps patients are taking it every other month, and we really can't account for that. So, there are certain limitations around these types of studies. We don't have reasons for discontinuation as well. So, there are some limitations.

Jason Freeman, MD, MBA: Dr Brown, thank you for helping us go through this important poster on persistence and adherence in ofatumumab, and thank you for your time today.

Brandon Brown, PharmD: Thank you for having me. This was fun.

Jason Freeman, MD, MBA: Thank you for watching CMSC 2023 Updates with Novartis US Medical Affairs.

Transcript Edited for Clarity