Sumatriptan Less Effective in Migraine With Aura

Sumatriptan is less effective in migraine attacks with aura than in those without, new data reveal.

The findings, from an analysis of previous clinical trial results, were presented here at the American Headache Society (AHS) 57th Annual Scientific Meeting by Jakob Møller Hansen, MD, PhD, a resident at the Department of Neurology at Rigshospitalet and also with the Danish Headache Center, Copenhagen, Denmark. He conducted the study during his postdoctoral fellowship at the University of California, Los Angeles.

The findings published May 5 in Neurology.

“The main point of our study is that attacks of migraine with aura vs. without aura may have different responses to different acute therapies. In the headache literature some studies find reduced efficacy of triptans administered during the aura. We are able to show that this may in fact be more broadly true for attacks with aura, and also, although to a lesser degree, patients with aura compared to patients without aura,” Dr Hansen said.

However, he noted, this finding doesn’t change the standing of triptans as first-line migraine treatment even in patients with aura.

“Our study suggests that a better understanding of these differential responses to therapy may be an important step to personalized medicine in acute migraine treatment,” he said. “Our results do not change earlier findings that sumatriptan is effective in acute migraine treatment. The current guidelines for sumatriptan are still valid.”

Indeed, session moderator Robert Shapiro, MD, PhD, professor in the Department of Neurological Sciences at the University of Vermont, Burlington said “I think the difference is significant, but it’s certainly not enough to change practice in terms of what you would initiate.”

What the data do suggest, Dr Shapiro said, is that “if patients who have a particular prominence of migraine with aura report that they’re not responding well to triptans, one might not be that surprised. And one might, based on the limited evidence presented, think in terms of using another agent.”

Effect Not Seen With Dihydroergotamine

Dr Hansen and colleagues examined pooled data from the Sumatriptan/Naratriptan Aggregated Patient database of 21 double-blind randomized trials in which the presence or absence of aura had been noted and 2-hour postdose pain-freedom status reported for adults with migraine aged 18 years and older.

A total of 2568 patients were randomly allocated to 100 mg sumatriptan and 1146 to placebo. Aura was present in 1199 attacks (847 sumatriptan/352 placebo), while 2515 were without aura (1721 sumatriptan/794 placebo).

The investigators also analyzed results from a single randomized, double-blind, placebo-controlledphase 3 study of an investigational orally inhaled dihydroergotamine (DHE), including 302 patients with aura (162 DHE/140 placebo) and 467 without aura (221 DHE/246 placebo).

With sumatriptan, pain-free rates at 2 hours were 32% for the patients without aura and 24% for those with aura, a significant difference (P < .001). No such distinction was seen with DHE, with 2-hour pain free rates of 29.4% for those without aura and 27.2% for those with aura (P = .65).

Compared with placebo, the therapeutic gain for sumatriptan was 23% for those without aura vs 16% for those with aura. For DHE, the therapeutic gain was 17.2% without aura and 20.0% with.

Numbers needed to treat for one 2-hour pain free outcome for sumatriptan were 4.4 without aura and 6.2 with aura. For DHE, those numbers were 5.8 and 5.0, respectively.

Remaining Questions

The reason for this differential effect is not clear, but Dr Hansen said one possible explanation is that migraine attacks that include cortical symptoms may involve more diffuse or severe derangements of brain physiology and thus may be more difficult to treat. Alternatively, attacks of migraine with aura may involve distinct mechanisms that result in different responses to therapy.

Remaining questions include whether these results would extend to other triptans or would differ by the various modes of triptan delivery, the timing of administration, or use of concomitant nonsteroidal anti-inflammatory drugs or prior opioids.

On the basis of the findings, Dr Shapiro advised, “If you have a patient with migraine with aura and they didn’t respond well to a triptan tablet, you might want to change the mode of delivery or change the triptan or change over to a DHE product.”

Dr Hansen said “Based on our results, we propose that future clinical trials should take care and classify the attack under treatment according to the International Classification of Headache Disorders, as suggested by the International Headache Society clinical trials subcommittee. More trials collecting reporting these data will be of great value and help us tailor the correct treatment for each patient.”