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Almotriptan for acute migraine

Meta-analysis
Results
Comment


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



Percent with outcome
Outcome
Almotriptan dose
(mg)
Almotriptan
Placebo
NNT
(95% CI)
Headache response 2 hours
6.25
55
35
5.0 (3.7 to 7.5)
12.5
61
35
3.8 (3.1 to 5.1)
25
64
35
3.5 (2.8 to 4.7)
Sustained response 24 hours
6.25
41
27
7.0 (4.8 to 13)
12.5
45
27
5.5 (4.1 to 8.2)
25
51
27
4.0 (3.2 to 5.6)
Pain free 2 hours
6.25
29
14
7.0 (5.1 to 11)
12.5
35
14
4.8 (3.8 to 6.3)
25
40
14
3.9 (3.1 to 5.1)
Sustained pain free 24 hours
12.5
26
11
6.8 (5.2 to 9.9)
Sustained pain free without adverse events
12.5
22
10
8.5 (6.2 to 14)



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:

  1. 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.

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