It is essential to recognize the clinical endpoints that are assessed in migraine drug trials when evaluating the medical literature and determining which triptan to utilize (Table 4). According to the International Headache Society, the recommended primary efficacy endpoint in migraine studies is being pain-free at two hours. Clinical endpoints common-ly overlooked include improvement of a patient’s quality of life and functional status.
Although these study endpoints are subjective, they are essential components to migraine research. A patient’s quality of life can be disrupted as a result of a migraine episode. Approximately 92% of all migraineurs have a disruption of normal activities during an attack and about 50% are forced to discontinue their daily activities. In a randomized multicentered study by Colman et al., almotriptan was compared to sumatriptan with respect to treatment satisfaction, functional status, and health-related quality-of-life issues.7 The study used a six-item survey to address the degree of quality-of-life issues (i.e., relief of symptoms, side effects experienced, duration of migraine relief, etc). Overall, there was no significant difference between the two groups with respect to pain relief at 48 hours (P=0.67). However, the almotriptan group had a higher rate of satisfaction and tolerability of side effects than sumatriptan (81.29 vs. 77.46, respectively; P=0.016). Improvement in functional status and quality of life was comparable among the two groups at 24 hours. The study concluded that although there were no differences in the time to achieve pain relief, the side effect profile of almotriptan was more desirable than sumatriptan. These results might help inform prescribers about potential benefits of almotriptan in terms of patient satisfaction.
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Table 4 International Headache Society Clinical Endpoints
|Headache response||Reduction of migraine intensity from moderate to severe to none or mild at a|
|point in time|
|Pain-free state||Decrease in migraine severity from moderate to severe to no pain at a given time|
|after medication administration|
|Time of pain relief||Chance of obtaining headache relief over time|
|Time to headache relief||Survival of the headache|
|Recurrence||The return of moderate to severe headache within 24 hours of treatment|
|following initial headache response at 2 hours|
|Complete or sustained pain-free response||Patient is pain-free at 2 hours with no recurrence or use of rescue medications|
|within 24 hours|
In the previously mentioned study, Spierings et al. observed similar results between almotriptan and sumatriptan. At two hours, 58% of patients in the almotriptan-treated group and 57% of patients receiving sumatriptan reported pain relief. However, more patients were pain-free at two hours in the group receiving sumatriptan (25% vs. 18%; P=0.005). There were no significant differences between the two groups in the number of patients reporting headache recurrence within 24 hours (27% in the almotriptan group vs. 24% of those receiving sumatriptan). As reported in previously mentioned studies, the incidence of adverse effects was significantly lower in patients taking almotriptan (9% vs. 16%; P=0.001).
There are several trials that have studied the safety and efficacy of almotriptan compared to placebo. Cabarrocas et al. performed a one-year open-label study with almotrip-tan 12.5 mg. The study objectives included assessment of safety and efficacy of a single dose of almotriptan in the treatment of migraine attacks in patients with a history of migraine for one year. Additional assessments included a written survey, which evaluated the presence of symptoms (i.e., pain intensity), the need for rescue medications (i.e., nonsteroidal anti-inflammatory drugs, analgesics, combination analgesics with or without opiate narcotics) and the time to next migraine. Results showed that of the 747 patients receiving the study drug, 43% of patients experienced pain relief after one hour of their first attack and 73% experienced relief at two hours. Back pain was the most common adverse event, reported in 51% of patients. Only 18 patients (7%) withdrew from the study because of adverse events. These results were shown to be similar to other placebo-controlled studies.
The efficacy and tolerability of almotriptan at varying doses in the treatment of migraine was assessed by Daholf et al. This double-blind controlled study randomized patients into one of four dosage regimens of almotriptan (i.e., 2, 6.25, 12.5 or 25 mg) as compared to placebo. Primary study endpoints were defined as a decrease in the severity of migraine pain two hours after treatment. Secondary endpoints assessed the use of escape medications, relief of associated migraine symptoms, and incidence of recurrence. The study found a dose-dependent response with respect to the number of patients who did not use escape medications within two hours after treatment. The 2-mg dose was comparable to that of placebo and the 25-mg dose showed no additional benefit over 12.5 mg. The incidence of adverse events was similar between the 12.5-mg dose and placebo, whereas there was an increase in adverse events (i.e., gastrointestinal and nervous-system-related) reported with the 25-mg dosage.
Ferrari and colleagues reviewed 53 clinical trials, including 24,000 patients, comparing all available trip-tans. The goal of this meta-analysis was to assist physicians in prescribing the most appropriate medication in the class. Primary outcomes were measurements of complete migraine relief within two hours after dose, recurrence of headache within 24 hours, and the lack of use of rescue medications. Additional assessments included tolerability of each triptan. Using sumatriptan as the standard, 12.5-mg almotriptan has similar efficacy after two hours of treatment, but with better tolerability and higher rates of pain-free intervals. canada drugs online
Further studies comparing almo-triptan to the newer triptans are necessary; however, with the trials available, almotriptan does have potential benefits. Almotriptan, like the other second-generation triptans, has improved pharmacokinetic properties, potency, and selectivity for the 5-HT1B/1D receptor. Based on results from comparative trials, almotriptan causes fewer adverse events—a desirable profile in a migraine medication. Although almotriptan is less likely to provide complete relief with two hours, it has been shown to relieve associated symptoms of migraines (i.e., nausea, vomiting, photophobia), allowing patients to return to their daily activities. Clinical responses to almotriptan and the others in its class do vary among migraineurs and so clinicians should be aware of this when choosing an appropriate treatment for a particular patient. Although pricing data shows almotriptan to be the least expensive in its class, pharma-coeconomic studies are needed to determine which 5-HT1B/1D agonist is the most cost-effective in the treatment of migraine (Table 1).