THERAPY

-Carmen Walsh-

A number of clinical trials have shown that naratriptan has greater efficacy and enhanced tolerability in the treat­ment of migraine headache, compared with sumatriptan.* Now researchers have shown that naratriptan is also effective in patients who do not respond to sumatriptan, is more effective in moderate compared with severe migraine attacks and appears to have a longer duration of action than zolmitriptan. The results of these Glaxo Wellcome­supported studies were presented at the 51st Annual Meeting of the American Academy of Neurology [Toronto, Canada; April 1999].

For 10 years the triptans have been under investigation for the treatment and prophylaxis of migraine and headache. The first triptan to reach the market in 1991, sumatriptan, provided a more effective treatment than older therapies for many patients.

However, approaching the millennium, second generation triptans, including naratriptan, are at the forefront of research and are characterised by improved oral bioavailability and more consistent therapeutic plasma drug concentrations which are achieved more quickly, compared with sumatriptan.

Relief for sumatriptan non-responders Although the efficacy of sumatriptan in treating

migraine is established, a small percentage of patients do not respond adequately to sumatriptan during a migraine attack.

Dr Stuart Stark from Alexandria, Virginia, US and colleagues from Glaxo Wellcome, Research Triangle Park, North Carolina, US, conducted a study to determine the efficacy and tolerability of naratriptan in patients with migraine who have had an unsatisfactory response to sumatriptan.!

In the study, 347 patients treated their first migraine attack with oral sumatriptan 50mg in order to confirm nonresponsiveness. Subsequently, 112 patients were not randomised to double-blind therapy with naratriptan or placebo because of a sufficient response to sumatriptan; the remaining patients treated their second migraine attack with a single oral dose of naratriptan 2.5mg (n = 99) or placebo (107).

Complete migraine relief observed The researchers said that the headache response**

rate at 2 hours postdose was significantly better for naratriptan, compared with placebo, recipients (25 vs 10% of patients, respectively). Similarly, at 4 hours postdose, the headache response rate was significantly better for naratriptan, compared with placebo, recipients (42 vs 20%, respectively). At 4 hours postdose, complete migraine relief was recorded amongst 22% of naratriptan recipients, compared with 10% of placebo recipients (p < 0.022).

Both sumatriptan and naratriptan were well tolerated, although fewer patients reported adverse events follow­ing naratriptan, compared with sumatriptan, adminis­tration. The incidence of adverse events related to naratriptan were throat/neck pain andlor pressure (2%) and parathaesia (1 %).

The researchers pointed out that the study high-lights the need to challenge patients before aban­doning sumatriptan therapy. They concluded that 'naratriptan 2.5mg tablets are an effective and well-tolerated alternative to sumatriptan in patients

1173-832419911190-000131$01.00° Adl.lntematlonal LlmItecl1999. All right. reserved

that have a history of unsatisfactory response to sumatriptan' .

Moderate vs severe migraine Another study conducted by Dr Martin Jones from

Greenford, UK, and colleagues (including researchers from Research Triangle Park) showed naratriptan to be effective and well tolerated in patients with nonsevere migraine.2

In the study, 374 patients treated 6835 moderate migraine attacks and 383 patients treated 6095 severe attacks, with a single oral dose of naratriptan 1 or 2.5mg. Patients had the option to take a second dose of naratriptan to treat persistent or recurrent headache.

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Outcome of naratriptan therapy according to migraine severity

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The researchers said that naratriptan was more effective in moderate, compared with severe, attacks [see figure]. A second dose of naratriptan was used to treat recurrence in 16% of moderate attacks and 15% of severe attacks. A second dose of naratriptan was used as rescue medication (in violation of study protocol) more frequently in severe attacks, compared with moderate attacks (22 vs 10%, respectively).

The incidence of adverse events after naratriptan administration was lower in moderate attacks, com­pared with severe attacks (12-15% vs 16-20%, respectively).

The researchers concluded that 'the tolerability and efficacy profiles of naratriptan render it particularly well-suitedfor the treatment of non­severe migraine attacks'.

Another study supported these data; it retrospect­ively compared the efficacy and tolerability of a single

• See Inphanna 1084: 9, 26Apr 1997; 800458523

•• Response was defined as severelmoderate pain reduced to miJdIno pain

Inphanna- 5 Jun 1999 No. 1190

13

14 THERAPY

oral dose of naratriptan 2.5mg with sumatriptan 100mg and placebo in 643 patients with moderate or severe migraine.3

Headache relief at 2 hours postdose for patients suffering from a moderate attack was reported by 66% of naratriptan recipients and 62% of sumatriptan recipients, compared with 45% of placebo recipients. Headache relief at 2 hours postdose in severe attacks was reported by 42, 58 and 21 % of patients in the respective treatment groups. Additionally, naratriptan had sustained activity in patients with moderate attacks, with 63% of patients reporting headache relief at 24 hours, compared with 58% of sumatriptan recipients and 29% of placebo recipients.

In patients suffering from moderate attack, the incidence of adverse events was not significantly different between naratriptan, sumatriptan and placebo recipients (16, 23 and 18%, respectively).

Once again, the researchers concluded that naratriptan is well suited for the treatment of nonsevere migraine attacks.

The longer lasting triptan Naratriptan appears to have a longer duration of

action in the treatment of migraine, compared with zolmitriptan, as shown by results from one of the first direct comparisons of the 2 drugs.4

In the randomised study, 200 patients treated ~ 3 migraine attacks with a single oral dose of naratriptan 2.5mg, oral zolmitriptan 2.5mg or placebo. Four hours after the first dose patients were permitted to take a second dose of study medication for headache recur­rence. Non-triptan rescue medication was allowed for persistent headache.

The researchers said that naratriptan had a longer duration of action compared with zolmitriptan and placebo [see table].

Naratriptan was also better tolerated compared with zolmitriptan. The overall incidence of adverse events was 23% for naratriptan recipients, 45% for zolmitriptan recipients and 15% for placebo recipients. The incidence

Inphanna-SJun 1999 No. 1190

of neurological events was lower for naratriptan, compared with zolmitriptan recipients (8 vs 17%, respectively) as was the incidence of cardiovascular events (1 vs 5%, respectively).

o"tit~ome .iJ:lpatie~tS with ·n· ligJraiIle therapy"";;'.

• Overall 24 hour efficacy = headache reBel 4 hours postdose wtth no ........... . use of rescue medication or second dose 01 study medication. with no;. worsening of headache 24 hours postdose .: '\/7

It should be noted that this trial was halted after enrolment of 200 patients because of logistical problems associated with supply of zolmitriptan (target enrolment was 728 patients).

1. Stark S, ct al. Naratriptan is effective for the treatment of migraine headache in sumatriptan non-responders. Neurology 52 (Supp\. 2): 2Cr7 (Poster), 12 Apr 1999 2. Jones M, ct al. Naratriptan tablets 2.5 mg are particularly effective and well­tolerated in non-severe migraine attacks: data from a one-year, open-label study.

Neurology 52 (Supp\. 2): 2Cr7-20S (Poster), 12 Apr 1999 3. o'Quinn s, et al. Naratriptan tablets 2.5 mg exhibit prolonged action and are well-tolerated in non-severe migraine attacks: data from a comparator study with sumatriptan.

Neurology 52 (Supp\. 2): 256-257, 12 Apr 1999 4. Schoenen J, ct al. Naratriptan 2.5-mg tablets have similar efficacy in the acute treatment of migraine as zolmitriptan 2.5-mg tablets, but exhibit a longer duration of action and are better tolerated: results of a comparator study. Neurology 52 (Supp\. 2): 257, 12 Apr 1999 10076213.

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