Cumulative Benefit With Anti-CGRPs in Real-World Experience

Stephen Silberstein, MD: How long do you wait when somebody is on an antibody before you give up? Let’s say you’ve come to my office and have an antibody—there’s no change—what are the chances of that patient doing better in a couple months? We analyzed that nonresponders at 1 month have a 40% chance they’ll have response within 3 months. It looks like, just as with the small molecules, we should wait 6 months. Originally, we thought they’d get better in a week. That’s not the answer. They can get better in a week, but it might take months.

Stephanie J. Nahas, MD, MSEd, FAHS, FAAN: Again, it is important how you define response and

nonresponse in that person.

Stephen Silberstein, MD: Fifty percent.

Stephanie J. Nahas, MD, MSEd, FAHS, FAAN: If there is zero response, I’m not sure we know how long you should continue subjecting that person to that treatment. My general philosophy is, if there is a signal of any kind of response, stick with it as long as possible to see how much you can get.

Deborah Friedman, MD, MPH: I’ve seen people in my practice who are coming in having tried 1 of the monoclonal antibodies for a month. I’ll say, “Well, what happened? Why did you stop after a month?” They say, “Well, because the doctor who prescribed it for me told me it was going to work within a week, and it didn’t work within a week, so we stopped it.” I think it’s really important to realize that was sort of an erroneous thought and they don’t work that fast on everybody.

Stephen Silberstein, MD: That’s exactly correct. The other point is that we have not done analyses of patients stratified by 10%, 20%, 30% and 40% response to see if there’s any relationship between that and long-term benefits. I can tell you, I’ve seen a number of patients now—first 2 or 3 shots, nothing. That third one, they start to feel something, and then 3 months later there’s a marked improvement. I think we need to look carefully, but I’m not ready to give up yet, and 6 months is a reasonable time.

Stephanie J. Nahas, MD, MSEd, FAHS, FAAN: I’ve even had a couple who had 0 until the fifth injection.

Stephen Silberstein, MD: OK.

Stewart J. Tepper, MD: Independently, with my difficult cases, patients with continuous headache, I wait 6 months before I consider an alternative.

Andrew Blumenfeld, MD: It’s what you would expect. If you’re switching off a peripheral system that’s sensitizing a central system, it may take time to have an effect on that central pathway.

Stephen Silberstein, MD: It’s a neuromodulation of the brain, as opposed to blocking an enzyme.

Stewart J. Tepper, MD: I do 3 cycles of onabotulinum A and wait at least another month after the third cycle before I make my decision.

Stephen Silberstein, MD: Have we published the data from the trials?

Stewart J. Tepper, MD: Correct.

Stephen Silberstein, MD: They clearly show that there are a number of people who respond in the second and third rounds who did not respond in the first one.

Andrew Blumenfeld, MD: The sequential benefit that you see with these medications is, the longer they get treated, the bigger the response. We’re seeing the same thing in the long-term studies of the monoclonal antibodies. Once you start responding, your response rate and your reduction in migraine days increases.

Stewart J. Tepper, MD: That’s an important point. We have the COMPEL study that you ran for onabotulinumtoxinA showing continued improvement for patients and cumulative benefit across 2 years. I tell my patients that. In the monoclonal antibody studies, for example, if one looks at the end of the 12-week randomized control trial—let’s take erenumab—40% of patients, regardless of dose, had about a 50% or greater reduction in mean monthly migraine days. At the end of a year with the 140 mg dose, over 40% of patients had at least a 75% reduction in their mean monthly migraine days. Mean monthly migraine days per month for chronic migraine dropped from 18 by 6 days per month at the end of 12 weeks, but from 18 days by 10 days per month with the 140 mg dose.

You can say to a patient, “With a 10-day drop per month, that’s 4 months of no migraine that you’re going to accrue by the end of the year of using a monoclonal antibody.” Nobody would say that’s a minimal clinical affect. That’s why I really don’t like to use placebo-controlled analyses to explain to patients what’s going on. It’s dropped from baseline; it’s cumulative benefit.

Andrew Blumenfeld, MD: I want to pick up on what Stew just said. Basically, I use that same data on the long-term open-label erenumab extension study that shows that, at 3 months, you have about a 6-day reduction. If you follow these patients out to the 16th month, you can see a 10- to 11-day reduction. When you present that to patients, it’s very encouraging to the patient to think, “If I stay on this drug for all this time, I will start to see this progressive improvement.” I think that’s a concept that patients often miss. They think, “Well, I’ve seen 6 days and that’s all I’m going to get.” In fact, they will get a lot more over time.