Elodie Ramos

Comparative efficacy of triptans for the abortive treatment of migraine: A multiple treatment comparison meta-analysis

Background Migraine is the most common neurological condition in developed countries. The abortive treatment of migraine attacks is important both for quality of life and costs associated with illness. Triptans, serotonin 5-HT1B/1D receptor agonists, effectively relieve the pain, disability, and associated symptoms of migraine while improving health-related quality of life. Although a number of direct head-to-head triptan comparisons have been made, data for all possible permutations are not available, and unlikely to ever be so, although in clinical practice such information would be useful. Objective We aimed to determine the relative efficacy of all available triptans to abort migraine headache among patients with previous adequate response to migraine treatments. Methods We included only double-blinded randomized clinical trials comparing triptans to either placebo or another triptan. Our primary outcomes were pain-free response at two hours and 24-hour sustained pain-free response, and our secondary outcomes were headache response at two hours and 24-hour sustained headache response. We used Bayesian multiple treatment comparison meta-analyses of seven triptans used in adult patients to abort migraine attacks. We applied a random-effects analysis with meta-regression adjusting for dose. Results are reported as odds ratios with 95% credible intervals. Results We included data from 74 randomized clinical trials. All triptans were significantly superior to placebo for all outcomes, with the exception of naratriptan for 24-hour sustained pain-free response. Eletriptan consistently yielded the highest treatment effect estimates. For the two-hour endpoints, eletriptan was statistically significantly superior to sumatriptan, almotriptan, naratriptan, and frovatriptan for at least one of the two outcomes. Rizatriptan yielded the second highest treatment effects followed by zolmitriptan. For the 24-hour endpoints, eletriptan was statistically significantly superior to sumatriptan, rizatriptan, almotriptan, and naratriptan for at least one of the two outcomes. Frovatriptan data were not available at that endpoint. Further, the probability that eletriptan is the most likely of all triptans to produce a favorable outcome was 68% for pain-free response at two hours, and 54% for 24-hour sustained pain-free response. Conclusion Triptans appear to offer differing treatment effects. In the populations studied eletriptan was most likely to produce pain-free responses that were sustained.

Anticoagulant use in patients with cancer associated venous thromboembolism: A retrospective cohort study

INTRODUCTION Long term anticoagulant therapy is recommended for treatment and secondary prevention of venous thromboembolism in cancer patients. We assessed outpatient anticoagulants [warfarin, low molecular weight heparins (LMWHs), fondaparinux and unfractionated heparin (UFH)] use in adult, cancer patients, 20years of age or older, who incurred a venous thromboembolism (primary or secondary in-hospital diagnosis) in Quebec, Canada between 2007 and 2009. MATERIALS AND METHODS Data were obtained from the Quebec Health Insurance Agency. Patients with an in-hospital cancer diagnosis between April 2007 and June 2009 and an in-hospital venous thromboembolism diagnosis either concurrently or consequently were eligible at the date of discharge (index date). Those patients registered with the provincial drug plan and discharged to the community were included in the study and followed for 6months. RESULTS Among 2,070 study patients, 72.4% received anticoagulant therapy at index date, 60% of whom were persistent with therapy and received it for ≥80% of follow-up days. Outpatient anticoagulant use was more likely in those with primary versus secondary diagnosis of venous thromboembolism and less likely in patients with cerebrovascular disease, peptic ulcer disease or previous anticoagulant use. The small number of patients who used either UFH (n=11) or fondaparinux (n=5) at index date were included in the LMWH group. Warfarin use was less likely than LMWH use in corticosteroid users, previous anticoagulant users, patients with metastatic cancer and those with catheter or chemotherapy in the previous three months. Warfarin use was more likely than LMWH use in: older patients, those residing in rural areas, those with lower income and those suffering from ischemic heart disease, atrial fibrillation or chronic kidney disease. Patients with ischemic heart disease were more likely to have used a non-dalteparin LMWH versus dalteparin (currently, the only LMWH approved by health Canada for chronic treatment of VTE), while those residing in rural areas and those with catheter/chemotherapy were less likely to have used them. A primary (versus secondary) discharge diagnosis of venous thromboembolism [Odds Ratio 1.42; 95% confidence interval (1.14, 1.76)], and metastatic cancer 1.27 (1.00, 1.60) were associated with persistence on anticoagulant treatment. CONCLUSION Guideline recommended outpatient use of anticoagulant in cancer patients hospitalized with venous thromboembolism was influenced by cancer status, old age and low income. Risk factors for bleeding prevented outpatient anticoagulant use in some patients.

Comparative tolerability of treatments for acute migraine: A network meta-analysis

Introduction Migraine headache is a neurological disorder whose attacks are associated with nausea, vomiting, photophobia and phonophobia. Treatments for migraine aim to either prevent attacks before they have started or relieve attacks (abort) after onset of symptoms and range from complementary therapies to pharmacological interventions. A number of treatment-related adverse events such as somnolence, fatigue, and chest discomfort have previously been reported in association with triptans. The comparative tolerability of available agents for the abortive treatment of migraine attacks has not yet been systematically reviewed and quantified. Methods We performed a systematic literature review and Bayesian network meta-analysis for comparative tolerability of treatments for migraine. The literature search targeted all randomized controlled trials evaluating oral abortive treatments for acute migraine over a range of available doses in adults. The primary outcomes of interest were any adverse event, treatment-related adverse events, and serious adverse events. Secondary outcomes were fatigue, dizziness, chest discomfort, somnolence, nausea, and vomiting. Results Our search yielded 141 trials covering 15 distinct treatments. Of the triptans, sumatriptan, eletriptan, rizatriptan, zolmitriptan, and the combination treatment of sumatriptan and naproxen were associated with a statistically significant increase in odds of any adverse event or a treatment-related adverse event occurring compared with placebo. Of the non-triptans, only acetaminophen was associated with a statistically significant increase in odds of an adverse event occurring when compared with placebo. Overall, triptans were not associated with increased odds of serious adverse events occurring and the same was the case for non-triptans. For the secondary outcomes, with the exception of vomiting, all triptans except for almotriptan and frovatriptan were significantly associated with increased risk for all outcomes. Almotriptan was significantly associated with an increased risk of vomiting, whereas all other triptans yielded non-significant lower odds compared with placebo. Generally, the non-triptans were not associated with decreased tolerability for the secondary outcomes. Discussion In summary, triptans were associated with higher odds of any adverse event or a treatment-related adverse event occurring when compared to placebo and non-triptans. Non-significant results for non-triptans indicate that these treatments are comparable with one another and placebo regarding tolerability outcomes.

An Open‐Label Trial of a Sumatriptan Auto‐Injector for Migraine in Patients Currently Treated With Subcutaneous Sumatriptan

To assess the ability of patients, during an acute migraine attack, to successfully self‐inject a single dose of sumatriptan using a novel sumatriptan auto‐injector (Alsuma®), and to evaluate the safety, tolerability, and effectiveness of this sumatriptan auto‐injector during an acute migraine attack.

Comparing the efficacy of eletriptan for migraine in women during menstrual and non-menstrual time periods: a pooled analysis of randomized controlled trials.

To assess the efficacy and tolerability of eletriptan in treating migraine attacks occurring within the defined menstrual time period of 1 day before and 4 days after onset of menstruation (menses days –1 to +4) compared with attacks occurring during non‐menstrual time periods (occurring outside of menses days –1 to +4).

Consistency of eletriptan in treating migraine: Results of a randomized, within-patient multiple-dose study

Objective The current study evaluated the consistency of eletriptan response. Methods Using a within-patient crossover design, patients with migraine completed a three-attack, open-label, lead-in period, before being treated, double-blind for four attacks, with either eletriptan 40 mg (ELE-40; N = 539) or eletriptan 80 mg (ELE-80; N = 432); placebo was randomly substituted for the treatment of one attack. Results On an a priori analysis of within-patient consistency, double-blind treatment was associated with similar 2 hour headache response rates using a ≥2/3 response criterion for ELE-40 (77%) and ELE-80 (73%), and using a 3/3 response criterion for ELE-40 (46%) and ELE-80 (47%). Within-patient consistency in achieving pain-free status at 2 hours using a ≥2/3 criterion was slightly higher on ELE-40 (42%) compared with ELE-80 (38%), and was similar using the 3/3 criterion (18% on ELE-40, 17% on ELE-80). On a repeated measures logistic regression analysis across all treated attacks, the probability of achieving a headache response at 2 hours ranged from 71% to 74% on ELE-40 vs. 17% to 28% on placebo (p < 0.0001), and from 66% to 74% on ELE-80 vs. 21% to 27% on placebo (p < 0.0001). The incidence, per attack, of adverse events was low for both ELE-40 and ELE-80. Few adverse events occurred with incidence ≥10% on ELE-40 (asthenia, 5.0%) or ELE-80 (asthenia, 10%; nausea, 5.8%). Discontinuations because of adverse events were 0.2% on ELE-40, and 1.6% on ELE-80 Conclusion In this multiple attack study, eletriptan was well-tolerated and demonstrated consistent and significant efficacy in the treatment of migraine. Clinicaltrials.Gov Identifier: NCT01859481

A review of the pharmacoeconomics of eletriptan for the acute treatment of migraine

Migraine is a commonly occurring, chronic disorder that can cause significant disability. Eletriptan, a selective serotonin 5-hydroxytryptamine 1 receptor subtype B/D (5-HT1B/1D) agonist, is a clinically effective treatment for moderate to severe migraine. The objective of this literature review was to summarize the available data on the pharmacoeconomics of eletriptan relative to other triptans. Articles meeting the following three criteria were included in the review: 1) contained pharmacoeconomic data on a marketed dose of eletriptan; 2) included data on at least one other comparator triptan; and 3) was in English. A MEDLINE® search yielded a total of eight studies (from the European Union [n=5] and from the USA [n=3]) across multiple regions. Seven of the studies examined the pharmacoeconomics of eletriptan relative to other triptans, and a further study examined the health care costs of eletriptan 40 mg versus sumatriptan 100 mg. Eletriptan 40 mg was among a group of triptans, including rizatriptan 10 mg and almotriptan 12.5 mg, demonstrating the greatest cost-effectiveness. This result held across different definitions of efficacy (2 hours pain-free, sustained pain-free, and sustained pain-free with no adverse events) and also held when cost-effectiveness models accounted for second doses and use of rescue medication, management of adverse events, and productivity loss, in addition to drug acquisition costs. Only limited head-to-head comparator data were available. The majority of pharmacoeconomic studies utilized the same set of efficacy and/or tolerability data, and indirect costs were rarely included despite the fact that the majority of per capita migraine costs are attributable to indirect costs. In summary, although the market is now dominated by generics, eletriptan 40 mg is among the most clinically and cost-effective oral triptans available for the management of acute migraine. Increased effectiveness/efficacy of eletriptan may necessitate a lesser need for other migraine treatments and/or switching to other triptans.

Outcome for headache and pain-free nonresponders to treatment of the first attack: A pooled post-hoc analysis of four randomized trials of eletriptan 40 mg

Objective The objective of this article is to evaluate, in first attack eletriptan headache and pain-free nonresponders, the efficacy of treating a second and third attack with the same dose of eletriptan 40 mg (ELE-40). Methods Data were pooled from four randomized, double-blind, placebo-controlled, multiple attack studies of eletriptan in the treatment of migraine. The first-attack eletriptan headache (HNR) and pain-free (PFNR) nonresponder samples consisted of patients who did not achieve headache or pain-free responses at two hours, or sustained headache or pain-free responses at 24 hours. The efficacy of the same dose of eletriptan (vs placebo; PBO) in treating the second and third attacks was evaluated using a logistic regression model. Results Among Attack 1 eletriptan HNRs, treatment with ELE-40 (vs PBO) was associated with significantly higher two-hour headache response and pain-free rates, respectively, on both Attack 2 (48.8% vs 20.2%; 17.0% vs 3.9%; p < 0.0001 for both comparisons) and Attack 3 (37.4% vs 15.5%; 18.8% vs 3.2%; p < 0.0001 for both comparisons). Significantly higher sustained headache response and pain-free rates at 24 hours were also observed on both Attack 2 and Attack 3. Conclusions The results of this pooled analysis suggest that patients who have HNR or PFNR to an initial dose of eletriptan may respond when a second and third attack is treated with the same dose.

An open-label trial of alsuma auto-injector for migraine

Methods This was an open-label, Phase 3 trial conducted at 10 sites in the US. Male or female adults, ages 18 to 60 years old, were eligible for study entry if they met IHS criteria for migraine with or without aura, with at least 2 attacks per month, and if they reported use of subcutaneous injectable sumatriptan on at least 2 occasions within the previous 2 months. During the onset of a migraine attack of moderate-to-severe intensity, patients were asked to administer a 6 mg subcutaneous dose of sumatriptan using the Auto-Injector. Subjects returned to the study site within 72 hours of the migraine for the post-treatment assessment visit.

Eletriptan provides consistent migraine relief: results of a within-patient multiple-dose study

Methods Patients first completed an open-label, lead-in period in which they treated 3 migraine attacks with eletriptan 40 mg. Based on response to open-label treatment, patients were treated with either eletriptan 40 mg (E40; N=539) or eletriptan 80 mg (E80; N=432) in a 4-attack consistency of response study in which placebo was substituted, in a randomized, double-blind fashion, for the treatment of one attack. Headache response was defined as improvement at 2 hours post-dose to a headache intensity of none (pain-free) or mild. Within-patient consistency was defined a priori as headache response at 2 hours on at least 2 out of 3 attacks.