Practical Implications of the STRIVE and ARISE Trials
A review of the results from the phase 3 STRIVE and ARISE trials looking at erenumab (Aimovig) as a preventive therapy for migraine, including anecdotes of personal experiences from 2 migraine experts.
Richard B. Lipton, MD, and Peter Goadsby, MBBS
PUBLISHED November 23, 2018
Current Series: Chronic Migraine Current Treatment Options And Recent Advances
Richard B. Lipton, MD: The ARISE trial compared 70 mg of erenumab with placebo in the preventive treatment of migraine. And again, of course, this is a drug given by injection. The study shows, overall, that about 40% of people who got [the] active drug and about 30% of people who got placebo had a 50% or greater reduction in monthly migraine days. And that standard of the 50% reduction in monthly migraine days is one standard metric that’s used in trials. The study also included an impact diary called the “MPFID” [Migraine Physical Function Impact Diary], and there was improvement in functional status on erenumab-treated patients versus placebo-treated patients.
Now, the truth is that the summary measures that emerge from trials don’t fully reflect the benefits of drugs that we see in practice, because in trials, for one thing, patients know they may be getting placebo and that attenuates the response rate. And for another thing, in practice, we don’t give placebo. So, the right way of measuring the benefit of a drug, in my opinion, is not by examining improvement relative to placebo but rather by examining the change made in patients’ lives, because that better reflects the experience we may well obtain in practice. So, the study demonstrates that erenumab is an effective preventive treatment for episodic migraine, and certainly my practice experience has confirmed that.
Peter Goadsby, MB BS: The so-called STRIVE study was a phase III episodic migraine preventive study. Patients were screened; they then had a 1-month baseline diary and 6 months of treatment. The last treatments were taken as the primary endpoint measurement. There was a reduction in migraine. There were 50% responses for the 70-mg dose, 43% for [the] 140-mg dose, and a 50% reduction in migraine days compared to 27% for placebo. Those reductions were paralleled by reductions in migraine-specific treatments and by improvements on the disability measures that were developed for the study. In STRIVE, the medicines were very well tolerated. [There was] some injection-site irritation, a couple of patients had some constipation compared to 1% on placebo, and a few people had some nasal symptomatology that’s branded as rhinitis, but it’s not clear at all what that is. Overall, the tolerability is excellent. None of the sort of problems that one sees with preventives we currently have—weight gain, cognitive problems, pins and needles—and really the simplicity of a monthly injection.
Richard B. Lipton, MD: I do not use erenumab as a first-line treatment. In many ways, based on what we know of its efficacy and safety profile, it might be justifiable to give it more broadly. But I tend to use erenumab in both episodic migraine and chronic migraine in patients who have significant levels of headache-related disability and who have not responded to conventional oral therapies.
At the moment, there is very little pushback in terms of prescribing erenumab, and I tend to use it in people who’ve tried and failed at least 2 conventional oral preventive medications—most often, 1 anti-epilepsy drug and 1 beta-blocker. But I’ve also used it in people who’ve tried and failed every trick I have in the book, because the drug has only recently become available.
So, I think the bottom-line is that it’s a very useful drug in patients with frequent headache who have significant disability, who have not gotten the benefits that they’re looking for from conventional oral preventives. In addition, on the chronic migraine side, for many years, onabotulinum toxin A [Botox] was the only preventive FDA-approved treatment for migraine. So, in my practice, if somebody gets onabotulinum toxin A and they have a great response [but] then they don’t, I have not been giving them erenumab. But if they have a partial response—let’s say they go from 25 headache days a month to 10 headache days a month—then I’ve been giving erenumab on top of onabotulinum toxin A and have seen substantial success doing that. I’ve also, in the chronic migraine setting, given it to as many patients who failed on onabotulinum toxin A and they’re no longer taking it because it doesn’t work.
Peter Goadsby, MB BS: Of the patients that I’ve seen that have used erenumab so far, they’ve actually done surprisingly good. I’ve been thinking about the CGRP mechanism for a long time, and it’s actually great to see people come back and have benefit and no downside to it. They’re happy with their improvement, and it’s an interesting interaction as a physician. One always feels less likely to discuss, because if something is working and there are no side effects, then we can agree that we can go ahead and there’s not much else to say apart from, “Happy to see you doing well.”