㈼−2- 4
複数のトリプタンをどう使い分けるか（有効性の差異， preference ，前兆期・予兆期の使用）

 

1) Ferrari MD, Goadsby PJ, Roon KI, Lipton RB. Triptans (serotonin, 5-
　 HT1B/1D agonists) in migraine: detailed results and methods of a meta-
　 analysis of 53 trials. Cephalalgia. 2002 Oct;22(8):633-58.
論文抄録
The triptans, selective serotonin 5-HT1B/1D agonists, are very effective acute migraine drugs. Soon, seven different triptans will be clinically available at 13 different oral doses, making evidence-based selection guidelines necessary. Triptan trials have similar designs, facilitating meta-analysis. We wished to provide an evidence-based foundation for using triptans in clinical practice, and to review the methodological issues surrounding triptan trials. We asked pharmaceutical companies and the principal investigators of company-independent trials for the 'raw patient data' of all double-blind, randomized, controlled, clinical trials with oral triptans in migraine. All data were cross-checked with published or presented data. We calculated summary estimates across studies for important efficacy and tolerability parameters, and compared these with those from direct, head-to-head, comparator trials. Out of 76 eligible clinical trials, 53 (12 not yet published) involving 24089 patients met the criteria for inclusion. Mean results (and 95% confidence intervals) for sumatriptan 100 mg, the first available and most widely prescribed oral triptan, are 59% (57-60) for 2 h headache response (improvement from moderate or severe to mild or no pain); 29% (27-30) for 2 h pain free (improvement to no pain); 20% (18-21) for sustained pain free (pain free by 2 h and no headache recurrence or use of rescue medication 2-24 h post-dose), and 67% (63-70) for consistency (response in at least two out of three treated attacks); placebo-subtracted proportions for patients with at least one adverse event (AE) are 13% (8-18), for at least one central nervous system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7). Compared with these data: rizatriptan 10 mg shows better efficacy and consistency, and similar tolerability; eletriptan 80 mg shows better efficacy, similar consistency, but lower tolerability; almotriptan 12.5 mg shows similar efficacy at 2 h but better sustained pain-free response, consistency, and tolerability; sumatriptan 25 mg, naratriptan 2.5 mg and eletriptan 20 mg show lower efficacy and better tolerability; zolmitriptan 2.5 mg and 5 mg, eletriptan 40 mg, and rizatriptan 5 mg show very similar results. The results of the 22 trials that directly compared triptans show the same overall pattern. We received no data on frovatriptan, but publicly available data suggest substantially lower efficacy. The major methodological issues involve the choice of the primary endpoint, consistency over multiple attacks, how to evaluate headache recurrence, use of placebo-subtracted proportions to control for across-study differences, and the difference between tolerability and safety. In addition, there are a number of methodological issues specific for direct comparator trials, including encapsulation and patient selection. At marketed doses, all oral triptans are effective and well tolerated. Differences among them are in general relatively small, but clinically relevant for individual patients. Rizatriptan 10 mg, eletriptan 80 mg and almotriptan 12.5 mg provide the highest likelihood of consistent success. Sumatriptan features the longest clinical experience and the widest range of formulations. All triptans are contra-indicated in the presence of cardiovascular disease.
文献 PubMed−ID
12383060
エビデンスレベル
㈵ a
文献タイトル (日本語)
片頭痛に対するトリプタン（セロトニン， 5-HT1B/1D作動薬）：53例のメタアナリシスの方法と詳細な結果
目的
トリプタンの臨床的使用にあたり妥当とするエビデンスを明らかにすること
研究デザイン
無作為二重盲検プラセボ対照比較試験のメタアナリシス
研究施設
多数
研究期間
２００１年まで
対象患者
５３件の臨床治験の２４０８９例
主要評価項目とそれに用いた
統計学的手法
服用２時間後頭痛反応性，頭痛消失率，頭痛消失時間の持続，再発，効果の定常性，副作用などの項目につき比較検討
結果

各種のトリプタンの有効率を計算して，最もよく使用されているスマトリプタン 100mgの結果と比較した．リザトリプタン10mgがより有効性と効果持続性に優れ同様の忍容性を示した．エレトリプタン80mgは有効性は優れ，同等の効果持続性だが忍容性は低かった．アルモトリプタン12.5mgはどの項目でも同様の結果を示した．スマトリプタン25mg，ナラトリプタン2.5mg，エレトリプタン20mgは有効性は低いが，忍容性は優れていた．ゾルミトリプタンなど他はほぼ同等の結果であった．
結論
通常市販の量では，トリプタンはいずれも有効であった．リザトリプタン 10mg，エレトリプタン80mg，アルモトリプタン12.5mgが定常的な有用性があった
コメント
大規模なメタアナリシス．質も高い．しかし，結果の解釈については議論が多い（特に細目について）
備考
 Publication Types:
•  Meta-Analysis

MeSH Terms:
•  Administration, Oral
•  Clinical Trials
•  Dose-Response Relationship, Drug
•  Human
•  Migraine/drug therapy*
•  Serotonin/adverse effects
•  Serotonin/pharmacokinetics
•  Serotonin/therapeutic use*
•  Serotonin Agonists/adverse effects
•  Serotonin Agonists/pharmacokinetics
•  Serotonin Agonists/therapeutic use*
•  Sumatriptan/administration & dosage
•  Support, Non-U.S. Gov't

Substances:
•  Serotonin Agonists
•  Sumatriptan
•  Serotonin
作成者
濱田　潤一

 

2) Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-
　 HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 　 trials. Lancet. 2001 Nov 17;358(9294):1668-75.

論文抄録

BACKGROUND: The triptans, selective serotonin 5-HT(1B/1D) agonists, are very effective acute migraine drugs with a well- developed scientific rationale. Seven different triptans will soon be clinically available, making evidence-based selection guidelines necessary. Triptan trials have similar designs, facilitating meta-analysis; this will provide a foundation for using triptans in clinical practice. METHOD: We asked pharmaceutical companies and the principal investigators of company-independent trials for raw patient data of all double-blind, randomised, controlled, clinical trials of oral triptans in migraine. We calculated summary estimates across studies for important efficacy and tolerability parameters, and separately summarised direct comparator trials. RESULTS: 53 clinical trials (12 unpublished) involving 24089 patients, met the criteria for inclusion. Mean results for 100 mg sumatriptan were 59% (95% CI 57-60) for 2 h headache response (improvement from moderate or severe to mild or no pain); 29% (27-30) for 2 h pain free (improvement to no pain); 20% (18-21) for sustained pain free (pain free by 2 h and no headache recurrence or use of rescue medication 2-24 h post dose); and 67% (63-70) for consistency (response in at least two of three treated attacks); placebo-subtracted proportions for patients with at least one adverse event (AE) were 13% (8-18), for at least one central nervous system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7). Compared with these data, 10 mg rizatriptan showed better efficacy and consistency, and similar tolerability; 80 mg eletriptan showed better efficacy, similar consistency, but lower tolerability; 12.5 mg almotriptan showed similar efficacy at 2 h but better other results; 2.5 mg naratriptan and 20 mg eletriptan showed lower efficacy and (the first two) better tolerability; 2.5 mg and 5 mg zolmitriptan, 40 mg eletriptan, and 5 mg rizatriptan showed very similar results. The results of the 22 trials that directly compared triptans show the same overall pattern. We received no data on frovatriptan, but publicly available data suggest lower efficacy. INTERPRETATION: At marketed doses, all oral triptans were effective and well tolerated. 10 mg rizatriptan, 80 mg eletriptan, and 12.5 mg almotriptan provide the highest likelihood of consistent success.

文献 PubMed−ID
11728541
エビデンスレベル
㈵ a
文献タイトル (日本語)

片頭痛急性期治療における経口トリプタン (セロトニン 5-HT(1B/1D)作動性薬剤)

目的
トリプタンの臨床的使用にあたり妥当とするエビデンスを明らかにすること
研究デザイン
無作為二重盲検プラセボ対照比較試験のメタアナリシス
研究施設
多数
研究期間
２００１年まで
対象患者
５３件の臨床治験の２４０８９例
主要評価項目とそれに用いた統計学的手法

服用２時間後頭痛反応性，頭痛消失率，頭痛消失時間の持続，再発，効果の定常性，副作用などの項目につき比較検討

結果

各種のトリプタンの有効率を計算して，最もよく使用されているスマトリプタン 100mgの結果と比較した．リザトリプタン10mgがより有効性と効果持続性に優れ同様の忍容性を示した．エレトリプタン80mgは有効性は優れ，同等の効果持続性だが忍容性は低かった．アルモトリプタン12.5mgはどの項目でも同様の結果を示した．スマトリプタン25mg，ナラトリプタン2.5mg，エレトリプタン20mgは有効性は低いが，忍容性は優れていた．ゾルミトリプタンなど他はほぼ同等の結果であった．

結論

通常市販の量では，トリプタンはいずれも有効であった．リザトリプタン 10mg，エレトリプタン80mg，アルモトリプタン12.5mgが定常的な有用性があった

コメント
大規模なメタアナリシス．結果の解釈については議論も多い．
備考
Publication Types:
•  Meta-Analysis

MeSH Terms:
•  Acute Disease
•  Administration, Oral
•  Human
•  Indoles/therapeutic use
•  Migraine/classification
•  Migraine/drug therapy*
•  Pyrrolidines/therapeutic use
•  Randomized Controlled Trials
•  Recurrence
•  Serotonin Agonists/therapeutic use*
•  Severity of Illness Index
•  Support, Non-U.S. Gov't
•  Treatment Outcome
•  Triazoles/therapeutic use

Substances:
•  Indoles
•  Pyrrolidines
•  Serotonin Agonists
•  Triazoles
•  eletriptan
•  rizatriptan
•  almotriptan
 
作成者
濱田　潤一

 

3) Geraud G, Olesen J, Pfaffenrath V, Tfelt-Hansen P, Zupping R, Diener
　 HC, Sweet R.Comparison of the efficacy of zolmitriptan and
　 sumatriptan: issues in migraine trial design. Cephalalgia. 2000
　 Feb;20(1):30-8.
論文抄録
In this international, multicentre, double-blind, placebo-controlled, single attack study, 'triptan naive' migraine patients were randomized in an 8:8:1 ratio to receive zolmitriptan 5 mg, sumatriptan 100 mg or placebo. The all-treated analysis included 1058 patients who took study medication. The primary endpoint, complete headache response, was reported by 39%, 38% and 32% of patients treated with zolmitriptan, sumatriptan and placebo, respectively, with no significant difference between treatment groups. In patients with moderate headache at baseline, complete response was significantly greater following zolmitriptan than after placebo (48% vs. 27%; P=0.01); there was no significant difference between sumatriptan and placebo groups (40% vs. 27%). In patients with severe baseline headache (where a greater reduction in headache intensity is required for a headache response), there was no significant difference between any groups in complete headache response rates. For secondary endpoints, active treatment groups were significantly superior to placebo for: 1-, 2- and 4-h headache response (e.g. 2-h headache response rates: zolmitriptan 59%; sumatriptan 61%; placebo 44%; P < 0.01 vs. placebo); pain-free response rates at 2 and 4 h; alleviation of nausea and vomiting; use of escape medication and restoration of normal activity. The incidence of adverse events was similar between zolmitriptan and sumatriptan groups but was slightly lower in the placebo group. The lack of difference between active treatments and placebo for complete response probably reflects the high placebo response obtained, which is probably a result of deficiencies in trial design. For example, the randomization ratio may result in high expectation of active treatment. Thus, while ethically patient exposure to placebo should be minimized, this must be balanced against the scientific rationale underpinning study design.
文献 PubMed−ID
10817444
エビデンスレベル
㈵ b
文献タイトル (日本語)
スマトリプタンとゾルミトリプタンの効果の比較：片頭痛の治験デザインにおける問題
目的
ゾルミトリプタンとスマトリプタンの効果を比較すること
研究デザイン
多施設無作為二重盲検プラセボ対照交差試験
研究施設
ヨーロッパ（国際）
対象患者
1058例
介入
トリプタン使用経験のない患者に無作為にプラセボとゾルミトリプタン 5mg，スマトリプタン100mgを1:8:8の割合で，割り付けてその効果を検討する．
主要評価項目とそれに用いた統計学的手法
一次エンドポイントは，完全な頭痛の反応（消失），二次エンドポイントは，１時間，２時間，４時間の頭痛反応性，頭痛消失率，悪心・嘔吐の反応，エスケープ薬剤使用．
結果
一次エンドポイントは，群間に有意な差はなかった．中等度の頭痛患者ではゾルミトリプタンがプラセボに比べて有意に良好（スマトリプタンは差なし）であった．重症頭痛では，差がなかった．二次エンドポイントでは１・２・４時間後の頭痛緩解，２・４時間後の頭痛消失率は有意に治療群でプラセボに比べて大であった．副作用はゾルミトリプタン群とスマトリプタン群で差がなかった．
結論
ゾルミトリプタンとスマトリプタンは有用性がある．しかし，一次エンドポイントはプラセボと差がなかった．双方の薬剤では効果に差を認めなかった．
コメント
中規模のスタディ．２剤の比較がより大規模かつ多くの評価項目をいれてなされるべきである．
備考
 Publication Types:
•  Clinical Trial
•  Multicenter Study
•  Randomized Controlled Trial

MeSH Terms:
•  Adolescent
•  Adult
•  Aged
•  Comparative Study
•  Double-Blind Method
•  Female
•  Human
•  Male
•  Middle Aged
•  Migraine/drug therapy*
•  Oxazoles/adverse effects
•  Oxazoles/therapeutic use*
•  Oxazolidinones*
•  Recurrence
•  Research Design
•  Serotonin Agonists/adverse effects
•  Serotonin Agonists/therapeutic use*
•  Sumatriptan/adverse effects
•  Sumatriptan/therapeutic use*
•  Support, Non-U.S. Gov't
•  Treatment Outcome

Substances:
•  Oxazoles
•  Oxazolidinones
•  Serotonin Agonists
•  Sumatriptan
•  zolmitriptan  
作成者
濱田　潤一

 

4) Gerth WC, McCarroll KA, Santanello NC, Vandormael K, Zhang Q,
　 Mannix LK. Patient satisfaction with rizatriptan versus other triptans:
　 direct head-to-head comparisons. Int J Clin Pract. 2001 Oct;55(8):552-6.
論文抄録
This study summarises the impact of treatment with rizatriptan 10 mg versus other 5-HT 1B/1D receptor agonists (triptans) on patient satisfaction with medication. Rizatriptan is a potent, selective 5-HT1B/1D receptor agonist shown to be fast, effective and well tolerated in the acute treatment of migraine. We investigated patients' overall satisfaction with treatment in studies in which direct comparisons with other triptans were made. Data from five double-blind, placebo-controlled trials in which rizatriptan 10 mg was compared with another triptan were included in the analysis. Rizatriptan 10 mg was compared with sumatriptan 100 mg in one parallel study (n = 916), sumatriptan 50 mg in two crossover studies (n = 1599), naratriptan 2.5 mg in one parallel study (n = 502), and zolmitriptan 2.5 mg in one parallel study (n = 701). Satisfaction was reported by patients on a seven-point scale ranging from 'completely satisfied, couldn't be better' to 'completely dissatisfied, couldn't be worse' at 2 hours after dosing. The percent of patients in the top two 'satisfied' categories (completely or very satisfied) were analysed. More patients on rizatriptan 10 mg were completely or very satisfied compared with sumatriptan 100 mg (33% vs 26%, p < 0.05), sumatriptan 50 mg (40% vs 35%, p < 0.05), naratriptan 2.5 mg (33% vs 19%, p < 0.01), and zolmitriptan 2.5 mg (38% vs 30%, p < 0.05). In all five studies more patients treated with rizatriptan 10 mg or other triptans were completely or very satisfied with treatment than patients receiving placebo (p < 0.001, except naratriptan vs placebo p = 0.004). The results, combined with the superior efficacy profile (fast, effective, well tolerated) of rizatriptan 10 mg, should enhance the treatment of migraine headache and lead to improved therapeutic intervention in clinical practice.
文献 PubMed−ID
11695077
エビデンスレベル
㈵ a
文献タイトル (日本語)
リザトリプタンと他のトリプタンに対する患者の満足度：直接比較
目的
リザトリプタン投与患者の総合的な満足度を他のトリプタンと比較する
研究デザイン
二重盲検プラセボ対照比較試験のメタアナリシス
対象患者
スマトリプタン 100mgとの比較９１６例，スマトリプタン50mgとの比較１５９９例，ナラトリプタンとの比較５０２例，ゾルミトリプタンンとの比較７０１例
介入
二重盲検プラセボ対照比較試験のメタアナリシス
主要評価項目とそれに用いた統計学的手法
７ポイントスケールによる満足度の評価．
結果
リザトリプタン 10mgを投与された患者では，スマトリプタン，ナラトリプタン，ゾルミトリプタンの投与患者より高い満足度を示した率が高値であった．また，プラセボとの比較をしている検討では，いずれのトリプタンもプラセボと比べ，高い満足度を示した．
結論
リザトリプタン 10mgは，早期の効果発現，有用性，良好な忍容性に加えて，治療上の優位性が明らかとなった．
コメント
メタアナリシスによりリザトリプタンの治療における優位性が示された．しかし，直接的な比較ではなく，問題も多い．
備考
Publication Types:
•  Meta-Analysis

MeSH Terms:
•  Adolescent
•  Adult
•  Aged
•  Clinical Trials, Phase III
•  Comparative Study
•  Double-Blind Method
•  Female
•  Human
•  Male
•  Middle Aged
•  Migraine/drug therapy*
•  Patient Satisfaction/statistics & numerical data*
•  Serotonin Agonists/therapeutic use*
•  Sumatriptan/therapeutic use
•  Support, Non-U.S. Gov't
•  Triazoles/therapeutic use*

Substances:
•  Serotonin Agonists
•  Triazoles
•  Sumatriptan
•  rizatriptan 
作成者
濱田　潤一

 

5) Steiner TJ, Diener HC, MacGregor EA, Schoenen J, Muirheads N, Sikes
　 CR. Comparative efficacy of eletriptan and zolmitriptan in the acute
　 treatment of migraine. Cephalalgia. 2003 Dec;23(10):942-52.
論文抄録
Eletriptan 40 mg and 80 mg have shown greater efficacy in acute migraine than oral sumatriptan 100 mg and naratriptan 2.5 mg. This study continues the systematic series of active comparator trials in the eletriptan clinical development programme. In a multicentre double-blind, double-dummy, parallel-groups trial, 1587 outpatients with migraine by IHS criteria were randomised in a 3: 3 : 3: 1 ratio to eletriptan 80 mg, eletriptan 40 mg, zolmitriptan 2.5 mg or placebo. Of these, 1312 treated a single migraine attack and recorded baseline and outcome data to be included in the intention-to-treat population. The primary analysis was between eletriptan 80 mg and zolmitriptan. For the primary efficacy end-point of 2-h headache response, rates were 74% on eletriptan 80 mg, 64% on eletriptan 40 mg, 60% on zolmitriptan (P < 0.0001 vs. eletriptan 80 mg) and 22% on placebo (P < 0.0001 vs. all active treatments). Eletriptan 80 mg was superior to zolmitriptan on all secondary end-points at 1, 2 and 24 h, in most cases with statistical significance. Eletriptan 40 mg had similar efficacy to zolmitriptan 2.5 mg in earlier end-points, and significantly (P < 0.05) lower recurrence rate and need for rescue medication over 24 h. All treatments were well tolerated; 30-42% of patients on active treatments and 40% on placebo reported all-causality adverse events that were mostly mild and transient. On patients' global ratings of treatment, both eletriptan doses scored significantly better than zolmitriptan.
文献 PubMed−ID
14984226
エビデンスレベル
㈵ b
文献タイトル (日本語)
片頭痛急性期治療のエレトリプタンとゾルミトリプタンの効果の比較
目的
片頭痛急性期治療においてエレトリプタンとゾルミトリプタンの効果を比較すること
研究デザイン
無作為二重盲検プラセボ対照比較試験
研究施設
多施設
対象患者
国際頭痛学会の診断基準を満たした外来の片頭痛患者１５８７例
介入
発作時の単回投与
主要評価項目とそれに用いた統計学的手法
一次エンドポイントはエレトリプタン 80mgとゾルミトリプタンの比較．２時間後の頭痛緩解で評価，二次エンドポイントは１時間，２４時間後の頭痛緩解・再発．
結果
２時間後の頭痛緩解率は，エレトリプタン 80mgで７４％，40mgで６４％，ゾルミトリプタンで６０％，これらはプラセボに比して有意に高値であった．他の二次エンドポイントでは，エレトリプタンはゾルミトリプタンより優れていた．エレトリプタン40mgは，ゾルミトリプタン2.5mgと比べ同等であったが，再発率は低かった．忍容性は同等であった．
結論
全般的なスケーリングで，エレトリプタンはゾルミトリプタンより優れた効果を有した．
コメント
大規模な比較試験．しかし，評価項目の設定，用量の設定など若干問題はある．解釈には注意が必要．
備考
Publication Types:
•  Clinical Trial
•  Multicenter Study
•  Randomized Controlled Trial

MeSH Terms:
•  Adolescent
•  Adult
•  Aged
•  Comparative Study
•  Dose-Response Relationship, Drug
•  Double-Blind Method
•  Female
•  Human
•  Indoles/administration & dosage*
•  Indoles/adverse effects
•  Linear Models
•  Male
•  Middle Aged
•  Migraine/drug therapy*
•  Migraine/physiopathology
•  Oxazolidinones/administration & dosage*
•  Oxazolidinones/adverse effects
•  Pyrrolidines/administration & dosage*
•  Pyrrolidines/adverse effects
•  Support, Non-U.S. Gov't

Substances:
•  Indoles
•  Oxazolidinones
•  Pyrrolidines
•  eletriptan
•  zolmitriptan 
作成者
濱田　潤一

 

6) Sandrini G, Farkkila M, Burgess G, Forster E, Haughie S; Eletriptan
　 Steering Committee. Eletriptan vs sumatriptan: a double-blind, placebo-
　 controlled, multiple migraine attack study. Neurology. 2002 Oct
　 22;59(8):1210-7.
論文抄録
OBJECTIVE: To compare the efficacy of oral eletriptan, 40 mg and 80 mg, and oral sumatriptan, 50 mg and 100 mg, in the acute treatment of migraine. METHODS: Patients with a history of migraine (n = 1,008) were randomly assigned to receive placebo, 40 mg of eletriptan, 80 mg of eletriptan, 50 mg of sumatriptan, or 100 mg of sumatriptan to treat up to three attacks. Early headache response (at 1 hour) was the primary endpoint, in addition to the standard endpoint, 2-hour headache response. RESULTS: Headache response rates were 12% at 1 hour and 31% at 2 hours for placebo; 24% at 1 hour and 50% at 2 hours for sumatriptan 50 mg; 27% at 1 hour and 53% at 2 hours for sumatriptan 100 mg; 30% at 1 hour and 64% at 2 hours for eletriptan 40 mg; and 37% at 1 hour and 67% at 2 hours for eletriptan 80 mg. More patients receiving eletriptan 80 mg achieved a 1-hour headache response than did patients receiving sumatriptan 50 mg (p < 0.05). All doses of eletriptan were superior to sumatriptan at 2 hours for headache response and complete pain relief (p < 0.05). Significantly more patients on eletriptan 80 mg achieved headache response in all attacks than did patients receiving either sumatriptan dose. Eletriptan 40 mg was superior to both sumatriptan doses in functional improvement (p < 0.005). The superior efficacy of both eletriptan doses was associated with higher rates of patient acceptability than sumatriptan 50 mg (p < 0.05). Eletriptan and sumatriptan were well tolerated. CONCLUSION: Oral eletriptan (40 mg and 80 mg) is effective, safe, and tolerable in the acute treatment of migraine and yields a consistent response.
文献 PubMed−ID
12391349
エビデンスレベル
㈵ b
文献タイトル (日本語)
エレトリプタンとスマトリプタン：二重盲検，プラセボ使用による片頭痛の多数の発作に対する検討
目的
片頭痛急性期治療において経口のエレトリプタンとスマトリプタンの効果を比較すること
研究デザイン
無作為二重盲検プラセボ対照比較試験
研究施設
多施設
対象患者
片頭痛の既往のある患者１００８例
介入
無作為にプラセボ，エレトリプタン 40mg，エレトリプタン80mg，スマトリプタン50mg，スマトリプタン100mgを割り付け，３回の発作で比較する
主要評価項目とそれに用いた統計学的手法
一次エンドポイントは，早期（１時間後）の頭痛反応（軽快）さらに二次として２時間後も評価する．
結果
頭痛反応率は，プラセボでは１時間後：１２％，２時間後：３１％であった．スマトリプタン 50mgでは１時間後：２４％，２時間後：５０％で，100mgでは１時間後：２７％，２時間後：５３％であった．一方，エレトリプタン40mgでは１時間後：３０％，２時間後：６４％，80mgでは１時間後：３７％，２時間後：６７％であった．スマトリプタン50mgに比べ，エレトリプタン80mgでは，有意に多数の患者が１時間後の軽快を認めた．エレトリプタンは，２時間後の頭痛軽快および頭痛完全消失率で，スマトリプタンより優れていた．他評価項目でもスマトリプタンよりエレトリプタンが優れているポイントがあった．双方の薬剤ともに忍容性は良好であった．
結論
経口エレトリプタンは，急性期の片頭痛治療において有効であり，比較でも優れている点があった．
コメント
大規模な RCT．結果の解釈にはより検討が必要．
備考
Publication Types:
•  Clinical Trial
•  Multicenter Study
•  Randomized Controlled Trial

MeSH Terms:
•  Adult
•  Comparative Study
•  Double-Blind Method
•  Female
•  Human
•  Indoles/adverse effects
•  Indoles/therapeutic use*
•  Logistic Models
•  Male
•  Middle Aged
•  Migraine/drug therapy*
•  Migraine/physiopathology
•  Migraine/prevention & control
•  Pyrrolidines/adverse effects
•  Pyrrolidines/therapeutic use*
•  Remission Induction
•  Serotonin Agonists/adverse effects
•  Serotonin Agonists/therapeutic use
•  Sumatriptan/adverse effects
•  Sumatriptan/therapeutic use*
•  Support, Non-U.S. Gov't

Substances:
•  Indoles
•  Pyrrolidines
•  Serotonin Agonists
•  eletriptan
•  Sumatriptan 
作成者
濱田　潤一

 

9) Olesen J, Diener HC, Schoenen J, Hettiarachchi J. No effect of
　 eletriptan administration during the aura phase of migraine. Eur J
　 Neurol. 2004 Oct;11(10):671-7.
論文抄録
Migraine aura is a warning sign readily recognized by patients. From the onset of aura it takes 30-60 min before the headache phase starts. Administration of acute medication during aura should provide sufficient time to achieve therapeutic plasma levels, counteracting the headache. To test this hypothesis we evaluated the efficacy of eletriptan 80 mg taken during aura. Patients met International Headache Society diagnostic criteria for migraine with aura, with an attack frequency of at least one per month and with aura occurring in > 50% of recent attacks. Of 123 patients randomized, 87 (71%) were treated with a double-blind, one attack, during the aura phase before headache, dose of either eletriptan 80 mg (n = 43; 74% female; mean age, 40 years), or placebo (n = 44; 82% female; mean age, 40 years). The primary outcome measure was the proportion of patients not developing moderate-to-severe headache within 6 h post-dose. There was no significant difference in the proportion of patients developing moderate-to-severe headache on eletriptan (61%) versus placebo (46%). Eletriptan was well tolerated and did not prolong the aura phase. Typical transient triptan adverse events were observed; most were mild-to-moderate in intensity. This study confirms the findings of two studies showing that triptans are ineffective but safe when given during the migraine aura phrase.
文献 PubMed−ID
PMID: 15469451
エビデンスレベル
㈽
文献タイトル (日本語)
片頭痛の前兆期に eletriptan は無効
目的
前兆期に eletriptan を内服するとその後起こる片頭痛発作を軽減させるかを検討する．
研究デザイン
無作為二重盲検プラセボ対照試験（ randomized, double-blind, placebo-controlled study ）
研究施設
Department of Neurology, Glostrup Hospital , Copenhagen , Denmark
研究期間
不明
対象患者
IHS の診断基準を満たす 87 人の前兆を伴う片頭痛患者で少なくとも 1 ヶ月に 1 回以上の発作を認め，発作の半分以上に前兆を伴う．
介入
平均年齢 40 歳， 43 人の女性が eletriptan80mg ，平均年齢 40 歳， 44 人の女性が placebo を前兆期に内服．
主要評価項目とそれに用いた統計学的手法
内服 6 時間以内に患者の頭痛が中等度から重度に進行する割合．
結果
内服 6 時間以内に患者の頭痛が中等度から重度に進行する割合は eletriptan 内服群で 61% placebo 内服群で 46% と有意差を認めなかった． Eletriptan 内服群で前兆期の遷延はなく，認容性も優れていた . 副作用は一般的なトリプタンに見られるものと同じで軽度から中等度であった．
結論
前兆期に内服しても重篤な副作用はないが，片頭痛発作には無効である．
コメント
無作為二重盲検プラセボ対照試験（ randomized, double-blind, placebo-controlled study ） ．
作成者
濱田潤一，清水利彦