Almotriptan for acute migraine
Migraine
is one of those conditions where continuous improvements have been made to
outcomes, in this case largely at the prompting of the International Headache
Society. Originally the outcome of interest was migraines with initial moderate
or severe pain becoming mild pain or no pain by two hours (headache response at
two hours).
Later,
pain free at two hours was used. Then the goalposts moved to incorporate not
just these two hour outcomes, but the additional requirement that patients with
the two hour outcome should maintain at least that level of pain relief for 24
hours without additional analgesic medication.
This
represents moving goalposts. The hurdle for effectiveness is increasingly
higher. One consequence or measure of the increasing difficulty is that
response rates with placebo fall from about 40% with the original outcome of
two-hour headache response to about 5% for pain free at two hours maintained to
24 hours. An individual patient analysis of almotriptan [1] takes things one
step further.
Meta-analysis
The
analysis was of four randomised, double-blind, placebo-controlled trials of
almotriptan for acute migraine. Several different doses were used, and all
analyses estimated efficacy for the first migraine attack.
Results
The
four trials had 2,294 patients, of whom 86% were women, and the mean age was 41
years. The main results calculated from data in the paper [1] are shown in
Table 1. As expected from other migraine trial data, NNTs were lower (better)
with both higher dose of almotriptan, and more easily attained outcome.
Table 1: Pooled analysis of four randomised trials of almotriptan compared with placebo in a migraine episode with moderate or severe pain
| Outcome | (mg) |
(95% CI) |
||
| Headache response 2 hours | ||||
| Sustained response 24 hours | ||||
| Pain free 2 hours | ||||
| Sustained pain free 24 hours | ||||
| Sustained pain free without adverse events | ||||
One
new outcome was the proportion of patients who were pain free at two hours, who
were without recurrence of moderate or severe headache pain, who had no
additional analgesics before 24 hours, and who reported no adverse events. For
this outcome, almotriptan 12.5 mg was successful for 22% of patients, compared
with 11% with placebo.
Comment
What
we can say is that almotriptan 12.5 mg is about as effective for treating acute
migraine as sumatriptan 100 mg, based on short-term outcomes at two hours. As
the hurdle gets higher, placebo responses fall (Table 1), just what we have
seen before.
What
is new is that, using individual patient data, we can now have at least one
outcome that has real relevance for patients. We know that 1 in 5 patients who
have an acute migraine attack and take the medicine will be pain free at two
hours, remain pain free up to 24 hours with no additional analgesic use, and
will not have any adverse events.
Pharmaceutical
companies may not like the message, because this way of looking at outcomes
implies that their drugs are not as good as they would like to think. So be it.
But there is another message for people who run or impose formularies: highly
limited formularies will mean that only a minority of patients may get the
benefits they want, for which of us can say whether those who do not benefit
with almotriptan would not benefit with another headache therapy, including
other triptans?
References:
- GC Dahlöf et al. Efficacy, speed of action and tolerability of almotriptan in the acute treatment of migraine: pooled individual patient data from four randomized, double-blind, placebo-controlled clinical trials. Cephalalgia 2006 26: 400-408.