Cost-benefit analysis of sumatriptan tablets versus usual therapy for treatment of migraine

We performed a systematic assessment of the costs and benefits of sumatriptan and usual therapy for migraine from society's perspective. A decision tree was constructed with probability estimates based on data from an open-label clinical trial assessing the economic and human impacts of sumatriptan and usual therapy on nursing personnel. Direct medical care costs including costs for drug, physician, and emergency room visits were considered. Benefits were estimated using the human capital approach based on the national average of weekly earnings and productivity loss estimated from a migraine clinical trial. The net benefits of sumatriptan and usual therapy for the treatment of a single migraine attack were estimated to be $50 and $20, respectively. The annual incremental net benefit of sumatriptan over usual therapy was estimated to be $114-540/patient. The price difference was offset by benefits of sumatriptan in reducing use of health care resources and productivity loss.     

Spotlight on rizatriptan in migraine

Rizatriptan is an orally active serotonin 5-HT(1) receptor agonist that potently and selectively binds to 5-HT(1B/1D) subtypes. Earlier clinical trials demonstrated that rizatriptan 5 or 10mg is more effective than placebo at providing pain relief and a pain-free state, relieving associated symptoms of migraine, normalising functional ability and improving patient quality of life, and showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recently, rizatriptan 10mg was shown to be more effective than zolmitriptan 2.5mg or naratriptan 2.5mg at producing a pain-free state 2 hours postdose. Furthermore, compared with naratriptan, significantly more patients who received rizatriptan were pain free or had pain relief from 1 hour onwards. The number of patients with normal functional ability at 2 hours was significantly higher after rizatriptan than after naratriptan or zolmitriptan. Rizatriptan was also generally more effective than zolmitriptan or naratriptan at relieving migraine-associated symptoms. Rizatriptan is generally well tolerated, and adverse events are usually mild and transient. The most common adverse events associated with rizatriptan in recent randomised trials were asthenia/fatigue, dizziness, somnolence and nausea. There was a trend towards a lower incidence of adverse events with rizatriptan compared with zolmitriptan (31.2 vs 38.8%). However, rizatriptan was associated with a significantly higher incidence of adverse events than naratriptan (39 vs 29%). The incidence of chest pain was similar after the administration of rizatriptan, zolmitriptan or naratriptan (2-4%). In conclusion, rizatriptan is an effective drug for the acute treatment of moderate or severe migraine. Oral rizatriptan 5 and 10mg have shown greater efficacy than placebo in providing pain relief, an absence of pain, relief from associated symptoms, normal functional ability and an improvement in patient quality of life. Earlier results showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recent studies have shown that rizatriptan 10mg provides faster pain relief and a higher percentage of patients with an absence of pain and normal functional ability at 2 hours than naratriptan 2.5mg or zolmitriptan 2.5mg. The efficacy of rizatriptan is retained when used in the long term, and the drug is generally well tolerated. Although well designed studies comparing rizatriptan with almotriptan, eletriptan and frovatriptan would further define the position of rizatriptan, current data suggest that rizatriptan should be considered as a first-line treatment option in the management of migraine.     

口服舒马曲坦治疗偏头痛83例

偏头痛患者８３例，男性１７例，女性６６例，年龄４０±ｓ９ａ，有１１９例次发作。口服舒马曲坦１００ｍｇ，４ｈ内显效率为７６．５％，好转率１３．４％，总有效率８９．９％。对偏头痛伴随症状恶心、呕吐和畏光、声的缓解率分别为９４％，９６％和９４％。出现较轻不良反应（１６％）。故舒马曲坦治疗偏头痛安全可行。     

Needle-free subcutaneous sumatriptan: in the acute treatment of migraine attacks or cluster headache episodes

A needle-free device for delivering a 6?mg fixed dose of sumatriptan into subcutaneous tissues has been developed and approved for the acute treatment of migraine and cluster headache in the US and some EU countries. In a pivotal registration study in healthy adult volunteers, a single dose of needle-free subcutaneous sumatriptan 6?mg demonstrated bioequivalence to a single dose of traditional, needle-based subcutaneous sumatriptan 6?mg when delivered into the abdomen or the thigh, but not the arm. In a noncomparative, multicentre, phase IV study, the administration of (one or two doses of) needle-free subcutaneous sumatriptan 6?mg consistently provided rapid and sustained relief from migraine pain and associated symptoms during the treatment of up to four migraine attacks over a period of up to 60 days among current triptan users. Moreover, the use of needle-free subcutaneous sumatriptan was associated with a significant improvement in treatment satisfaction in these patients who were less than 'very satisfied' with their usual symptomatic therapy. Needle-free subcutaneous sumatriptan was generally well tolerated in the phase IV study. Although the overall adverse event profile of the needle-free delivery system was similar to that previously reported for the needle-based delivery system, it was associated with a numerically higher incidence of administration/injection-site reactions in clinical trials that enrolled healthy adult volunteers.     

Comparing dihydroergotamine mesylate and sumatriptan in the management of acute migraine. A retrospective cost-efficacy analysis

The annual cost of managing migraine totals billions of US dollars. This retrospective economic analysis of a clinical trial comparing subcutaneous dihydroergotamine mesylate (DHE) with subcutaneous sumatriptan in the treatment of acute migraine is appropriate because, although each product has been shown to be efficacious, the acquisition cost of sumatriptan is over 3 times that of DHE. Total costs in each treatment group were calculated and applied independently to 11 clinical trial efficacy measures. Three of the efficacy measures showed no statistically significant difference between treatment arms, leading to a decision to use the less expensive DHE. In 4 of the efficacy measures. DHE was the obvious choice because it is more efficacious and less expensive. For the final 4 efficacy measures, where sumatriptan is more efficacious and more expensive, incremental cost-efficacy ratios were calculated to determine the additional expenditure required to achieve outcomes associated with quick relief. Depending on the efficacy variable chosen and the assumptions used in the model, the incremental cost-efficacy ratios ranged from $US4000 to $US6700 per year (1993 dollars) for each additional patient who is successfully treated with sumatriptan compared with DHE. Therefore, in a population of 100 migraineurs, an additional 13 to 22 patients would achieve these short term benefits of sumatriptan, although it would cost an additional $US88 395 annually, given the assumptions made. Because each product has unique advantages, we conclude that the more cost-efficacious product is dependent on the outcome of interest and the amount that the patient or provider is willing to pay to achieve that outcome.     

Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine.

Sumatriptan and the ergot alkaloids are useful tools for deciphering drug mechanisms in migraine and related headaches. Both neuronal and vascular mechanisms have been proposed on the basis of actions of 5-HT at receptors resembling the 5-HT1D subtype. In this Viewpoint article, Michael A. Moskowitz argues that blockade of neural transmission and the neurogenic inflammatory response provides a mechanism by which sumatriptan and ergot alkaloids alleviate vascular headaches. He postulates, with similar arguments, that sumatriptan and ergot alkaloids may block headaches that develop from meningovascular inflammatory disorders such as from viral and bacterial meningitis and from the sequelae of head injury.     

Cost-effectiveness analysis of stratified versus stepped care strategies for acute treatment of migraine: The Disability in Strategies for Care (DISC) Study

BACKGROUND: The Disability in Strategies for Care (DISC) study was the first large randomised controlled trial to compare alternative treatment strategies in the acute treatment of migraine. With 835 patients in its intention-to-treat efficacy analysis, DISC compared a stratified care strategy, where initial therapy was based on clinical need as determined by the Migraine Disability Assessment Scale (MIDAS) and two stepped care strategies (across attacks and within attacks), where first-line therapy with a simple combination analgesic was escalated, if response had been inadequate, to zolmitriptan, a migraine-specific therapy. OBJECTIVE: To report on the cost effectiveness of these three strategies from a societal perspective. STUDY DESIGN AND METHODS: A cost-effectiveness analysis was undertaken using data from the DISC study, and including both health service and productivity costs. Data were collected prospectively on drug usage (main therapy and rescue medication); resource use associated with adverse events was estimated by a clinician blinded to treatment strategy. Health service resource use was costed using UK unit costs (1999 to 2000 values). Data were collected using diary cards on the amount of time patients lost from work, and on reduced effectiveness at work, due to a migraine attack. This facilitated an estimate of the productivity costs associated with the treatment strategies. To assess cost effectiveness, the differences in costs between the strategies were related to the two primary outcome measures in the trial: headache response 2 hours after initial therapy and disability-adjusted time during the first 4 hours after initial therapy. RESULTS: Although the mean health service cost was higher in the stratified care group (mean over 6 attacks of pound 28.25 versus pound 11.74 and pound 23.15 in the stepped care across attacks group and within attacks group, respectively), mean productivity costs over 6 attacks were lower in the stratified group (pound 112.22 versus pound 144.70 and pound 127.53). The total mean cost over six attacks was, therefore, lowest in the stratified care group (pound 138.95 compared with pound 157.19 in the stepped care across attacks group and pound 148.53 in the stepped care within attacks group), although these differences did not reach statistical significance. In terms of headache response, stratified care was statistically significantly more effective than both forms of stepped care. Using disability-adjusted time, stratified care was statistically significantly more effective than stepped care across attacks, but not against stepped care within attacks. CONCLUSION: Given its lower mean costs and higher mean effectiveness, a stratified care strategy, which included zolmitriptan, was the dominant strategy and was unequivocally more cost effective from a societal perspective than either stepped care strategy. When the uncertainty around these means was considered, stratified care had the highest probability of being cost effective.     

AVP-825: a novel intranasal delivery system for low-dose sumatriptan powder in the treatment of acute migraine

Introduction: Migraine is a common, disabling disorder, and many patients remain dissatisfied with existing treatments. AVP-825 (ONZETRA® Xsail®) is a Breath Powered® exhalation delivery system for low-dose sumatriptan nasal powder (22 mg) that has been recently approved for use in the treatment of acute migraine with or without aura in adults. AVP-825 takes advantage of unique features of nasal anatomy and physiology to avoid limitations typically seen with other types of intranasal medication delivery.

Areas covered: This review provides a summary of the pharmacology, clinical efficacy and tolerability of AVP-825 in clinical studies to date and also provides an overview of the unique aspects of the delivery system.

Expert commentary: AVP-825 represents an improvement in nasal delivery of sumatriptan for migraine. PK studies indicate a distinct advantage of AVP-825 over traditional liquid nasal sprays in terms of absorption time, which may underlie the early efficacy observed with AVP-825. It offers the benefits of non-oral medications at a comparatively low sumatriptan dose, without the limitations associated with more invasive approaches. AVP-825 is suitable for use across multiple phases of a migraine attack from use as an early intervention to use in a more advanced migraine with nausea, given the non-oral application.     

Efficacy,end points and eventualities: sumatriptan/naproxen versus butalbital/paracetamol/caffeine in the treatment of migraine

Evaluation of: Derosier F, Sheftell F, Silberstein S et al. Sumatriptan–naproxen and butalbital: a double-blind, placebo-controlled crossover study. Headache 52(4), 530–543 (2012).

Migraine is a widespread, relapsing, remittent syndrome. No animal model predicts whether test medications will be clinically useful. Using a modern, well-controlled, sophisticated study design, Derosier et al. demonstrates not only that a butalbital formulation has modest efficacy as an acute treatment for migraine but also that a sumatriptan–naproxen combination is superior. These conclusions are reached using a variety of internally consistent secondary efficacy end points. The primary end point chosen (highly conservative and fashionable in some academic circles) was a technical failure (and not a negative experimental finding). Migraine is intrinsically pleiomorphic: diverse treatment options help match patient with therapy. This study does not justify blanket bans on (admittedly hazardous) barbiturate therapies, and regulators should not impose end point conservatism to an extent that will stifle further progress.     

养血清脑丸联合利扎曲普坦治疗偏头痛的临床研究

目的 探讨养血清脑丸联合苯甲酸利扎曲普坦片治疗偏头痛的临床疗效.方法 选取2019年5月—2020年5月在漯河市中心医院就诊的118例偏头痛患者,按照随机数字法分为对照组(59例)和治疗组(59例).对照组口服苯甲酸利扎曲普坦片,10 mg/次,3次/d.治疗组在对照组基础上口服养血清脑丸,2.5 g/次,3次/d.两...     

天舒胶囊联合舒马普坦治疗偏头痛的临床研究

目的探讨天舒胶囊联合舒马普坦治疗偏头痛的临床疗效。方法选取2018年3月—2019年3月在平顶山市第二人民医院进行治疗的88例偏头痛患者,根据用药的差别分为对照组(44例)和治疗组(44例)。对照组口服琥珀酸舒马普坦片,25 mg/次,1次/d;治疗组在对照组基础上口服天舒胶囊,1.36 g/次,3次/d。两组均经过4周治疗后进行效果比较。观察两组的临床疗效,比较两组治疗前后相关评分、血清学指标的变化情况。结果经过治疗,对照组有效率为81.82%,显著低于治疗组97.73%,两组比较差异有统计学意义(P0.05)。治疗后,两组头痛程度、头痛发作次数、头痛持续时间和头痛伴随症状等评分均较治疗前显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后,治疗组这些症候评分明显低于对照组,两组比较差异具有统计学意义(P0.05)。两组PSQI评分、GQOLI-74评分、VAS评分均较治疗前显著改善,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后,治疗组这些相关量表评分的改善程度优于对照组,两组比较差异具有统计学意义(P0.05)。两组血清环氧化酶-2(COX-2)、神经元特异性烯醇酶(S-NSE)、基质金属蛋白酶-9(MMP-9)、血栓素B2(TXB2)、5-羟色胺(5-HT)水平均较治疗前显著下降,而β-内啡肽(β-EP)水平均显著升高,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组这些血清学指标改善程度优于对照组,两组比较差异具有统计学意义(P0.05)。结论天舒胶囊联合舒马普坦治疗偏头痛具有较好的临床疗效,可有效改善患者临床症状,改善机体相关血清学指标水平,提高患者睡眠及生活质量,具有一定的临床推广应用价值。     

Intranasal sumatriptan: in adolescents with migraine

Sumatriptan, a serotonin 5-HT(1B/1D) agonist, constricts cranial blood vessels and inhibits neuroinflammatory processes. A single dose of sumatriptan 10 mg (approved European dosage) was significantly more effective than placebo in achieving headache relief at 1 hour post-dose in a well designed study. Headache relief occurred in significantly more adolescents administered a single dose of intranasal sumatriptan 20 mg (at 1 and 2 hours) and 5 mg (at 2 hours) than placebo (pooled data from two studies). Sustained headache relief (1-24 and 2-24 hours) occurred in significantly more recipients of a single dose of intranasal sumatriptan 20mg and 5mg than placebo (pooled data from two studies). Intranasal sumatriptan was generally well tolerated in adolescent migraineurs (in single-episode studies or long term in multiple-episode studies). Taste disturbance occurred more often with intranasal sumatriptan than with placebo [Chart: see text].     

A comparison of the cost-effectiveness of almotriptan and sumatriptan in the treatment of acute migraine using a composite efficacy/tolerability end point

OBJECTIVE: To use a composite efficacy/tolerability end point to compare the cost-effectiveness, from the perspective of a U.S. health care payer, of almotriptan and sumatriptan in the treatment of an acute migraine attack. METHODS: The composite end point.Sustained pain free and No Adverse Events. (SNAE) was created from the sustained pain free and adverse event rates obtained in a meta-analysis of 53 placebo-controlled trials of oral triptans. The total direct cost of treating a single migraine attack was calculated from published sources. RESULTS: In the base-case analysis, the average cost-effectiveness ratios (CERs) were 82 US dollars , 133 US dollars , and 138 US dollars (per attack at which SNAE is achieved, 2004 prices) for almotriptan 12.5 mg, sumatriptan 50 mg, and sumatriptan 100 mg, respectively; the incremental CERs for almotriptan 12.5 mg were 12 US dollars and 16 US dollars (compared with sumatriptan 50 mg and sumatriptan 100 mg, respectively) per incremental attack at which SNAE is achieved. Sensitivity analyses were conducted to explore the impact of (1) relaxing the base-case assumptions (independence of efficacy and tolerability, uniform apportionment of health service use costs across attacks, number of tablets used to treat 1 attack); (2) varying input costs; and (3) uncertainty in the efficacy and tolerability estimates from the meta-analysis. In all of these sensitivity analyses, almotriptan 12.5 mg remained cost effective compared with sumatriptan 50 mg and 100 mg. CONCLUSION: Almotriptan was economically superior to sumatriptan in the treatment of a migraine attack.     

Cost-effectiveness analysis of enoxaparin versus unfractionated heparin in the secondary prevention of acute coronary syndrome

BACKGROUND: The Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 11B studies revealed that enoxaparin reduced the incidence of death, myocardial reinfarction and recurrent angina in patients with acute coronary syndrome (ACS) compared with unfractionated heparin (UFH). OBJECTIVE: To perform a pharmacoeconomic analysis to evaluate the cost effectiveness of treatment with enoxaparin compared with UFH in Spanish patients with ACS. DESIGN AND SETTING: Retrospective cost-effectiveness analysis using data and costs from Spanish sources, conducted from the perspective of the National Health System. PATIENTS, INTERVENTIONS AND OUTCOMES MEASURES: The study was based on the results of the ESSENCE and TIMI 11B clinical trials, which included more than 7,000 patients with ACS treated with enoxaparin or UFH. The main variables studied were the success rate, expressed as patients with no complications (reinfarction, unstable angina or death), and the decrease in the utilisation of healthcare resources (revascularisation procedures and hospitalisation). RESULTS: The base-case results of the analysis showed superior efficacy and lower total treatment and follow-up costs with enoxaparin compared with UFH. The total savings in direct health costs per patient with enoxaparin ranged between 448 and 659 euros (time horizons of 1 month and 1 year, respectively) [2001 values]. The sensitivity analysis results confirmed the advantage of enoxaparin in all cases, except in one scenario: when simultaneously using all the minimum values of the confidence interval for absolute risk reduction (ARR) in the utilisation of health resources. CONCLUSIONS: This study suggests that enoxaparin is a more effective and less expensive treatment option than UFH in secondary prevention of patients with ACS in Spain, confirming the results obtained in other pharmacoeconomic analyses performed in the UK, USA, France and Canada.     

丹七软胶囊联合舒马普坦治疗偏头痛的临床研究

目的探讨丹七软胶囊联合舒马普坦治疗偏头痛的临床疗效。方法选取2017年1月—2019年4月于天津医科大学第二医院进行治疗的偏头痛患者126例,随机分为对照组和治疗组,每组各63例。对照组口服琥珀酸舒马普坦片,100 mg/次,1次/d。治疗组在对照组的基础上口服丹七软胶囊,5粒/次,3次/d,两组均连续治疗4周。观察两组的临床疗效,比较两组治疗前后头疼发作情况、血清基质金属蛋白酶-9(MMP-9)的变化情况。结果治疗组治疗总有效率(95.24%)优于对照组(82.54%)(P0.05)。治疗后两组患者头疼发作频次、发作程度评分均显著降低,头疼发作持续时间均显著缩短(P0.05);治疗后,治疗组头疼发作情况显著优于对照组(P0.05)。治疗后,两组患者MMP-9均显著降低(P0.05);且治疗后治疗组MMP-9显著低于对照组(P0.05)。结论丹七软胶囊联合舒马普坦治疗偏头痛具有较好的临床疗效,能够有效改善患者血液流变学指标,减少头痛发作,具有一定的临床推广应用价值。     

A review of rizatriptan,a quick and consistent 5-HT1B/1D agonist for the acute treatment of migraine

Rizatriptan is a second-generation triptan marketed as 5 and 10 mg tablets and rapidly disintegrating wafer formulations. In > 5000 acute migraine patients enrolled in short-term trials and almost 1800 patients in long-term, open-label trials treating ~ 47,000 attacks, rizatriptan was effective and well-tolerated. Controlled head-to-head data and a meta-analysis of 53 randomised, placebo-controlled trials of oral triptans in > 24,000 patients have shown that rizatriptan 10 mg offers efficacy advantages over oral sumatriptan 50 and 100 mg and other oral triptans, both in terms of speed of onset of action and consistency. These advantages may reflect its improved pharmacological profile over sumatriptan in terms of higher oral bioavailability and a shorter time to maximum concentration. The wafer formulation offers the convenience of being administered without water. As a result of its superior efficacy profile and generally good tolerability, rizatriptan can be considered as a first-line treatment for acute migraine.     

A review of rizatriptan, a quick and consistent 5-HT1B/1D agonist for the acute treatment of migraine

Rizatriptan is a second-generation triptan marketed as 5 and 10 mg tablets and rapidly disintegrating wafer formulations. In > 5000 acute migraine patients enrolled in short-term trials and almost 1800 patients in long-term, open-label trials treating approximately 47000 attacks, rizatriptan was effective and well-tolerated. Controlled head-to-head data and a meta-analysis of 53 randomised, placebo-controlled trials of oral triptans in > 24000 patients have shown that rizatriptan 10 mg offers efficacy advantages over oral sumatriptan 50 and 100 mg and other oral triptans, both in terms of speed of onset of action and consistency. These advantages may reflect its improved pharmacological profile over sumatriptan in terms of higher oral bioavailability and a shorter time to maximum concentration. The wafer formulation offers the convenience of being administered without water. As a result of its superior efficacy profile and generally good tolerability, rizatriptan can be considered as a first-line treatment for acute migraine.