Data from the long-term study of erenumab are very surprising in the sense that many of the patients continued to have significant results which continued for the duration of the study, said Stephen Silberstein, MD, professor of neurology at Thomas Jefferson University and director of the Headache Center at Jefferson Health.
Data from the long-term study of erenumab is very surprising in the sense that many of the patients continued to have significant results which continued for the duration of the study, said Stephen Silberstein, MD, professor of neurology at Thomas Jefferson University and director of the Headache Center at Jefferson Health.
The American Journal of Managed Care® (AJMC®): Can you give a brief overview of your work?
Dr. Silberstein: I've been doing headache medicine now for over 40 years, and basically, I grew into it like many of us who have been in it for a while. Over the course of my lifetime, I've been involved in the development of every major, acute and preventative treatment for migraine. Starting with the triptans, and now, most recently, botox, now, the monoclonal antibodies.
AJMC®: What were the results of the 5-year open-label extension study on long term safety of erenumab for episodic migraine?
Dr. Silberstein: I think it's really important to note that patients with migraine will be taking medicines for a long time. One of the questions we've always asked is, as the patient continues to take the medicine for a long time, will any safety concerns show up that we did not see early on in the studies. This is a long term extension of patients with episodic migraine for the placebo-controlled double-blind trial. First, we found that the patients did very well. If you look at some of the data, it's very surprising in the sense that many of the patients continued to have significant results continued for the duration of the study. For example, if you look at 50%, 75%, and 100% reduction migraine days that's 65.7%, compared to 69.3%, in the last 4 weeks. Almost half of the patients had a 75% reduction, and almost 35%, actually all 36%, had no pain in the last 4 weeks. But this is extremely important information, so we actually show that.
Now the other question we're going to ask about is, what about adverse events? And basically speaking, we had 100 patient-years and there were 123 adverse events. Nasopharyngitis was the most common with upper respiratory infection, but that's very common in anybody if they're on a drug for 5 years. Those were the most frequent. Significant adverse events occurred in 49 patients, and basically most were single occurrences. Remember in a clinical trial if you get hit by a car while you're on a medicine, that's considered a significant adverse event. There were 2 fatal events reported. One patient had atherosclerosis and death of an unknown cause. An autopsy was not performed. These were previously reported. The safety signals were consistent with those observed in earlier trials without increases over the 5 years. So this really tells us the following: some of our concerns about continuing the medication for a long period of time have been allayed, because up to 5 years, we did not see anything that we didn't see earlier. Patients are 5 years older and despite the aging process, there were no significant increased adverse events demonstrated in our trial.
AJMC®: How many patients continued with the treatment from baseline and what were the main reasons for stopping?
Dr. Silberstein: Three hundred and eighty-three patients were enrolled in the open label phase and then after a mean of 2 years, patients all got a higher dose of 140 milligrams. One hundred and thirty two patients discontinued erenumab prior to the dose increase and 35 discontinued erenumab treatment while receiving the higher dose. People will stop for a lot of reasons. It's been my experience with a number people on antibodies, the headaches go away. Remember this was an episodic headache population, episodic migraine population. It is quite conceivable that with the passage of time, they may not have needed the drug anymore because none on the discontinuations were actually related to the fact they had significant adverse events. Many patients discontinued treatment when there was a protocol amendment requiring a switch to a higher dose. If you look at other trials, like some of the antiepileptic drugs, they have a much higher withdrawal rate. The discontinued rates due to adverse events with low. Five percent of those discontinued over 5 years, which is much lower than any other thing. So we know that patients discontinued for reasons other than adverse events. The trend of blood pressure increase, about 2 to 3 millimeters of mercury over 5 years, is very similar to the increased blood pressure with age that was reported in the Framingham study. Basically, if we look at everything, and what's happening, we find it's really consistent with what's going on. The other point I would point out is that in the double-blind control constipation was noted. The rates of constipation in this analysis was 1.8 per 100 patient-years or lower, and that was a double-blind study. This is a consistent observation, constipation occurs early and tends to dissipate over time.