Healthcare resource utilization and associated costs among patients with migraine in Finland: A retrospective register-based study.

Migraine is a common chronic brain disorder, characterized by recurring and often disabling attacks of severe headache, with additional symptoms such as photophobia, phonophobia and nausea. Migraine affects especially the working age population. The objective of this retrospective observational register-based study was to analyze the use of healthcare services and associated costs in Finnish migraine patients. Study was based on aggregate data from January 1st, 2020, to December 31st, 2021, from the Finnish Institute for Health and Welfare's national registries. Patients were grouped into nine patient groups according to medication prescriptions and diagnoses. Healthcare resource utilization in specialty, primary, and occupational healthcare was assessed and analyzed separately for all-cause and migraine related healthcare contacts from a one-year period. The total number of patients was 175 711, and most (45%) of the patients belonged to a group that had used only one triptan. Migraine related total healthcare resource utilization was greater for patients that had used two or more triptans compared to those that had used only one. The patients with three or more preventive medications had the highest total migraine related healthcare resource utilization of the studied patient cohorts. Of the total annual healthcare costs 11.5% (50.6 million €) was associated to be migraine related costs. Total per patient per year healthcare costs were highest with patients that had used three or more preventive medications (5 626 €) and lowest in those with only one triptan (2 257 €). Our findings are in line with the recent European Headache Federation consensus statement regarding the unmet need in patients who have had inadequate response to two or more triptans. When assessing the patient access and cost-effectiveness of novel treatments for the treatment of migraine within different healthcare systems, a holistic analysis of the current disease burden along with potential gains for patients and healthcare service providers are essential information in guiding decision-making.

Triptans and vascular comorbidity in persons over fifty: Findings from a nationwide insurance database - A cohort study.

OBJECTIVE: To gather information about prescription of triptans and to evaluate whether vascular comorbidity differs in users and nonusers of triptans over the age of 50 years. BACKGROUND: Beyond the age of 50 years, migraine is still common-yet the incidence of vascular disorders increases. Triptans, medications for treating migraine attacks, are vasoconstrictive drugs and contraindicated in persons with vascular disorders. METHODS: Based on a nationwide insurance database from 2011, we compared the prescription of vascular drugs (identified by Anatomical Therapeutic Chemical codes), vascular diagnoses and hospitalizations, between triptan users greater than 50 years and a matched control group. RESULTS: Of the 3,116,000 persons over 50 years, 13,833 (0.44%) had at least one triptan prescription; 11,202 (81%) were women. Thirty percent of the triptan users (13,833/47,336 persons) were over 50 years. Of those over 50 years, 6832 (49.4%) had at least one vascular drug and 870 (6.3%) had at least one inpatient vascular diagnosis; 15.7% (2166 of 13,833 users) overused triptans. We compared triptan-users to 41,400 nonusers, using a 1:3 match. In triptan-users, prescriptions of cardiac therapies and beta blockers were significantly more common (odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.24-1.47 and OR = 1.19, 95% CI = 1.14-1.25, respectively); whereas prescriptions of calcium channel blockers and renin/angiotensin inhibitors were significantly less common (OR = 0.82, 95% CI = 0.76-0.88 and OR = 0.75, 95% CI = 0.72-0.79, respectively). The prescriptions of antihypertensive, diuretic, and antilipidemic drugs as well as platelet inhibitors and direct thrombin inhibitors did not differ in users and nonusers. Triptan users had significantly more hospital stays (OR = 1.39, 95% CI = 1.33-1.45); however, the number of days spent in the hospital and more importantly the frequency of inpatient vascular diagnoses did not differ statistically significantly between the two groups. CONCLUSION: In persons over 50 years of age, a prescription of triptans is common. Vascular comorbidity is comparable in users and nonusers of triptans showing that triptans are prescribed despite vascular comorbidity and suggesting that triptan use does not increase vascular risk in patients with migraine over the age of 50 years. Nevertheless, regular evaluation for contraindications against triptans and for vascular risk factors is recommended in this age group.

Understanding the migraine treatment landscape prior to the introduction of calcitonin gene-related peptide inhibitors: Results from the Assessment of TolerabiliTy and Effectiveness in MigrAINe Patients using Preventive Treatment (ATTAIN) study.

BACKGROUND: Calcitonin gene-related peptide (CGRP) inhibitors were introduced in the United States (US) in 2018. To understand the changing patterns of preventive treatment following the introduction of these new agents, we must first characterize the patterns which preceded their introduction. OBJECTIVE: To characterize the burden, unmet need, and treatment patterns in patients with migraine initiating preventive migraine medications before the introduction of CGRP inhibitors in the US. METHODS: Between March 2016 and October 2017, we enrolled episodic (EM) and chronic migraine (CM) patients initiating or changing preventive treatment at primary care or neurology clinic visits in the US, in a real-world observational study using a prospective cohort design. At baseline and monthly thereafter for 6 months, we collected data from study sites and patients on migraine frequency, treatment modifications, migraine impact on functioning, and work productivity for a descriptive analysis of migraine patient experience and treatment patterns. RESULTS: From the sample of 234 completers, 118 had EM (50.4%) and 116 had CM (49.6%). Mean age at enrollment was 41 years (SD = 12) and mean age at first migraine diagnosis was 22 years (SD = 11). Most participants were females (n = 204/234; 87.2%) and white (n = 178/234; 76.1%). The majority (n = 164/234; 70.1%) had not used preventive migraine treatment in the 5 years prior to enrollment (treatment naïve). At baseline, mean monthly migraine days were 9.6 days (SD = 5.0) for the preventive treatment naïve group and 12.4 days (SD = 7.0) for treatment experienced patients. The majority had severe Migraine Disability Assessment (Grade IV, total score ≥21), including 67.1% (n = 110/164) of the preventive treatment naïve and 77.1% (n = 54/70) of the preventive treatment experienced patients. Headache Impact Test total scores indicating severe impairment (score >59) occurred in 88.4% (n = 145/164) of the treatment naïve and 88.6% (n = 62/70) of treatment experienced patients. Mean work productivity loss as measured by the Work Productivity and Activity Impairment questionnaire in the subsample of employed patients was 53.3% loss. The most used acute medications at baseline were nonsteroidal anti-inflammatory agents (n = 124/234; 53.0%), acetaminophen-based products (n = 112/234; 47.9%), and triptans (n = 105/234; 44.9%). The most commonly initiated preventive treatments were topiramate (n = 100/234; 42.7%), tricyclic antidepressants (n = 39/234; 16.7%), beta-blockers (n = 26/234; 11.1%), and onabotulinumtoxinA (n = 24/234; 10.3%). Over the 6-month follow-up period, almost half of patients (n = 116/234, 49.6%) modified their preventive treatment and discontinued treatment (n = 88/312 total modifications; 28.2%) or modified their pattern of use by increasing, decreasing, or skipping doses (n = 224/312 total modifications; 71.8%), often without seeking medical advice. Avoiding side effects was the main reason reported among patients who discontinued (n = 52/88; 59.1%), decreased frequency or dose (n = 37/89; 41.6%), and skipped doses (n = 29/86; 33.7%). Perceived lack of efficacy was another frequent reason reported among those who discontinued (n = 20/88; 22.7%), decreased frequency or dose (n = 15/89; 16.9%), and skipped doses (n = 18/86; 20.9%). Despite initiation of preventive treatment and improvements observed in number of headache and migraine days, migraine patients continued to experience substantial disability, headache impact, and reduced productivity throughout the 6-month follow-up period. CONCLUSIONS: Prior to 2018, the burden of migraine was high for patients initiating preventive treatments. Despite having more than 9 days of migraine per month on average, the majority (70.1%) of patients initiating prevention had been treatment naïve, indicating underuse of preventive treatments. The preventive treatments used in this study were poorly tolerated and were reported by patients to lack efficacy, resulting in suboptimal adherence. The high discontinuation rates suggest that the preventive medications being offered during the period of the study did not meet the treatment needs of patients. In addition, the decisions by about half of patients to alter their prescribed treatment plan without consulting their provider can pose substantial health risks. These findings pertain to the broad set of preventive treatments initiated in this study and do not support inferences about individual preventive treatments, due to limitations in sample size. These findings suggest the need for more effective and better tolerated preventive treatment options.

Headache characteristics and burden from chronic migraine with medication overuse headache: Cross-sectional observations from the Medication Overuse Treatment Strategy trial.

OBJECTIVE: To describe headache characteristics, medication use, disability, and quality of life in a large patient cohort from the United States who have chronic migraine (CM) and medication overuse headache (MOH). METHODS: In all, 610 adult patients were enrolled into the Medication Overuse Treatment Strategy trial from 34 healthcare clinics, including headache specialty, general neurology, and primary care clinics. Descriptive statistics characterize baseline demographics, headache characteristics, medication use, disability (Headache Impact Test 6 [HIT-6] and Migraine Functional Impact Questionnaire [MFIQ]), pain interference (PROMIS Pain Interference), and quality of life (EQ-5D-5L). Relationships with headache frequency were assessed. RESULTS: Mean age was 45 years (SD 13) and 531/608 (87.3%) were females. Mean headache days per 30 was 24.3 (SD 5.5), including 13.6 (SD 7.1) with moderate to severe headache. Daily headaches were reported by 36.1% (219/607) of patients. Acute headache medications were used on 21.5 (SD 7.5) per 30 days. The most commonly overused medications were simple analgesics (378/607, 62% of patients), combination analgesics (246/607, 41%), and triptans (128/607, 21%). HIT-6, MFIQ, PROMIS Pain Interference, and EQ-5D-5L scores demonstrated substantial negative impact from CM with MOH on patient functioning and quality of life. Higher headache frequency was associated with more moderate-severe headache days, more frequent acute headache medication use, greater headache-related disability, and lower quality of life. Only 272/606 (44.9%) were taking migraine preventive medication. CONCLUSIONS: CM with MOH is associated with a large burden on patients in the United States. Higher headache frequency is associated with greater impact on functioning, pain interference, and quality of life.

The effectiveness and value of novel acute treatments for migraine.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Agboola, Borrelli, Rind, and Pearson are employed by ICER. Touchette, through the University of Illinois at Chicago, received funding from ICER for development of the economic model described in this publication. Atlas has nothing to disclose.

A global real-world assessment of the impact on health-related quality of life and work productivity of migraine in patients with insufficient versus good response to triptan medication.

BACKGROUND: Migraine is a chronic, disabling neurological disease characterized by moderate-to-severe headache pain with other symptoms, including nausea, vomiting, and photophobia. Triptans, while generally effective, are insufficiently efficacious in 30-40% of patients and poorly tolerated by or contraindicated in others. We assessed the impact of insufficient response to triptans on health-related quality of life (HRQoL) and work productivity in patients currently receiving any prescribed triptan formulation as their only acute migraine medication. METHODS: Data were from the 2017 Adelphi Migraine Disease Specific Programme, a cross-sectional survey of primary care physicians, neurologists, and headache specialists and their consulting patients with migraine in the USA, France, Germany, Italy, Spain, and UK. Triptan insufficient responders (TIRs) achieved freedom from headache pain within 2 h of acute treatment in ≤3/5 migraine attacks; triptan responders (TRs) achieved pain freedom within 2 h in ≥4/5 attacks. Multivariable general linear model examined differences between TIRs and TRs in HRQoL and work productivity. Logistic regression identified factors associated with insufficient response to triptans. RESULTS: The study included 1413 triptan-treated patients (TIRs: n = 483, 34.2%; TRs: n = 930, 65.8%). TIRs were more likely to be female (76% vs. 70% for TIRs vs TRs, respectively; p = 0.011), older (mean age 42.6 vs. 40.5 years; p = 0.003), and had more headache days/month (7.0 vs. 4.4; p < 0.001). TIRs had significantly more disability, with higher Migraine Disability Scores (MIDAS; 13.2 vs. 7.7; p < 0.001), lower Migraine-specific Quality of Life scores, indicating greater impact (Role Function Restrictive: 62.4 vs. 74.5; Role Function Preventive: 70.0 vs. 82.2; Emotional Function: 67.7 vs. 82.1; all p < 0.001), and lower EQ5D utility scores (0.84 vs. 0.91; p = 0.001). Work productivity and activity were impaired (absenteeism, 8.6% vs. 5.1% for TIRs vs. TRs; presenteeism, 34.3% vs. 21.0%; work impairment, 37.1% vs. 23.3%; overall activity impairment, 39.8% vs. 25.3%; all p < 0.05). CONCLUSION: HRQoL and work productivity were significantly impacted in TIRs versus TRs in this real-world analysis of patients with migraine acutely treated with triptans, highlighting the need for more effective treatments for patients with an insufficient triptan response. Further research is needed to establish causal relationships between insufficient response and these outcomes.

Comparison of healthcare resource utilization and costs among patients with migraine with potentially adequate and insufficient triptan response.

BACKGROUND: Triptans are the most commonly prescribed acute treatments for migraine; however, not all triptan users experience adequate response. Information on real-world resource use and costs associated with triptan insufficient response are limited. METHODS: A retrospective claims analysis using US commercial health plan data between 2012 and 2015 assessed healthcare resource use and costs in adults with a migraine diagnosis newly initiating triptans. Patients who either did not refill triptans but used other non-triptan medications or refilled triptans but also filled non-triptan medications over a 24-month follow-up period were designated as potential triptan insufficient responders. Patients who continued filling only triptans (i.e. triptan-only continuers) were designated as potential adequate responders. All-cause and migraine-related resource use and total (medical and pharmacy) costs over months 1-12 and months 13-24 were compared between triptan-only continuers and potential triptan insufficient responders. RESULTS: Among 10,509 new triptan users, 4371 (41%) were triptan-only continuers, 3102 (30%) were potential triptan insufficient responders, and 3036 (29%) did not refill their index triptan or fill non-triptan medications over 24 months' follow-up. Opioids were the most commonly used non-triptan treatment (68%) among potential triptan insufficient responders over 24 months of follow-up. Adjusted mean all-cause and migraine-related total costs were $5449 and $2905 higher, respectively, among potential triptan insufficient responders versus triptan-only continuers over the first 12 months. CONCLUSIONS: In a US commercial health plan, almost one-third of new triptan users were potential triptan insufficient responders and the majority filled opioid prescriptions. Potential triptan insufficient responder patients had significantly higher all-cause and migraine-related healthcare utilization and costs than triptan-only continuers.

The Headache Pipeline: Excitement and Uncertainty.

There are many new treatment options available for migraine and more are coming. Three calcitonin gene-related peptide (CGRP) antagonist monoclonal antibodies have been approved and a 4th is due in early 2020. Small molecule CGRP receptor-blocking oral compounds, both for acute care and prevention, are also coming. Four neurostimulators are available, with others on the way. New acute treatments coming soon include the 5HT1F agonist lasmiditan, a zolmitriptan intradermal micro-needle patch, and a nasal mist sumatriptan with a permeability enhancer. Farther out, three novel dihydroergotamine delivery systems, and a liquid-filled capsule of celecoxib show early promise. A new, safer form of methysergide is in the works, as is a longer-duration onabotulinumtoxinA. As always with new products, questions regarding safety, tolerability, cost, and insurance coverage will need to be addressed. Despite these concerns and uncertainties, a robust headache treatment pipeline is good for patients who are not satisfied with the results of their treatment and/or cannot tolerate existing treatments.

Assessment Of Spanlastic Vesicles Of Zolmitriptan For Treating Migraine In Rats.

OBJECTIVE: To develop and evaluate zolmitriptan spanlastics (Zol SLs) as a brain-targeted antimigraine delivery system. Spanlastics (SLs) prepared using span 60: tween 80 (70:30%, respectively) gave the highest percentage of entrapment efficiency (EE%). MATERIALS AND METHODS: A total of 60 adult male Wistar albino rats were divided into six groups (n=10 rats/group). Group 1 (Control) comprised rats serving as a negative control. Group 2 was treated with glyceryl trinitrate (NTG) and served as the positive control. Groups 3 (NTG+Zol com), Group 4 (NTG+Zol sol) and Group 5 (NTG+Zol SLs) received commercial zolmitriptan orally, zolmitriptan solution intranasally and Zol SLs F5 intranasally, respectively, 30 min before NTG. Group 6 (Zol SLs) comprised normal rats that received only Zol SLs intranasally. RESULTS: We found decreased Tmax, increased Cmax, AUC0-6, AUC0-∞ and ameliorated behaviour in rats (head scratching) treated with intranasal SLs compared to oral commercial zolmitriptan. CONCLUSION: Our study substantiates the enhanced efficacy of Zol SLs in brain targeting for migraine treatment.

Cost-Effectiveness of Reclassifying Triptans in Australia: Application of an Economic Evaluation Approach to Regulatory Decisions.

BACKGROUND: Migraine is a common, chronic, disabling headache disorder. Triptans, used as an acute treatment for migraine, are available via prescription in Australia. An Australian Therapeutic Goods Administration (TGA) committee rejected reclassifying sumatriptan and zolmitriptan from prescription medicine to pharmacist-only between 2005 and 2009, largely on the basis of concerns about patient risk. Nevertheless, pharmacist-only triptans may reduce migraine duration and free up healthcare resources. OBJECTIVES: To estimate the cost-effectiveness of reclassifying triptans from prescription-only to pharmacist-only in Australia. METHODS: The study design included decision-analytic modeling combining data from various sources. Behavior before and after reclassification was estimated using medical practitioner and patient surveys and also administrative data. Health outcomes included migraine frequency and duration as well as adverse events (AEs) discussed by the TGA committee. Efficacy and AEs were estimated using randomized controlled trials and observational studies. RESULTS: Reclassifying triptans will reduce migraine duration but increase AEs. This will result in 337 quality-adjusted life-years gained at an increased cost of A$5.9 million over 10 years for all Australian adults older than 15 years (19.6 million). The incremental cost-effectiveness ratio was estimated to be A$17 412/quality-adjusted life-year gained. CONCLUSIONS: The incremental cost-effectiveness ratio is likely to be considered cost-effective by Australian decision makers. Serotonin syndrome, a key concern of the TGA committee, had little impact on the results. Further research is needed regarding pharmacist-only triptan use by migraineurs currently using over-the-counter medicines and by nonmigraineurs, the efficacy of triptans, and the risk of cardiovascular and cerebrovascular AEs and chronic headaches with triptans.

[Rizatriptan: experience after 15 years of clinical use]. / Rizatriptan: experiencia tras 15 años de uso clinico.

We review the development of rizatriptan, one of the seven 5-HT1B/1D agonists available for the symptomatic treatment of migraine, emphasizing the most relevant contributions carried out from our country. Rizatriptan has shown the quickest onset of action, both in controlled studies and in the different metaanalyses, which translates in high efficacy levels at two hours. Its tolerability and safety profile is similar to that of the other compounds in this pharmacological group. Postlaunching studies have shown that its high efficacy leads to pharmacoeconomic savings and to a robust preference and satisfaction by the patient for this triptan. Its efficacy is improved with an early use within migraine attacks and recent data have shown also efficacy in adolescents. This global profile places rizatriptan as a triptan of first choice for any kind of migraine attacks.

TITLE: Rizatriptan: experiencia tras 15 años de uso clinico.En este trabajo se pasa revista al desarrollo del rizatriptan, uno de los siete agonistas 5-HT1B/1D disponibles para el tratamiento sintomatico de la migraña, prestando especial atencion a las aportaciones mas relevantes llevadas a cabo desde España. El rizatriptan ha demostrado ser el triptan con inicio de accion mas rapido, tanto en estudios comparativos controlados como en diversos metaanalisis, lo que se ha traducido en elevados niveles de eficacia a las dos horas. El perfil de seguridad y tolerabilidad de este triptan es similar al del resto de los compuestos de este grupo farmacologico. Los estudios poscomercializacion han evidenciado que su eficacia se traduce en ahorro farmacoeconomico y preferencia y satisfaccion del paciente con este triptan. Su eficacia mejora con su uso precoz dentro de la crisis de migraña, y datos recientes indican que el rizatriptan es util tambien en preadolescentes. Este perfil global posiciona al rizatriptan como un triptan de eleccion para cualquier tipo de crisis de migraña.

Cost-effectiveness of oral triptans for acute migraine: mixed treatment comparison.

BACKGROUND: The cost-effectiveness of triptans in the treatment of migraine has not been assessed since generic sumatriptan entered the Finnish market in 2008. METHODS: Using systematic review and mixed treatment comparison, the effectiveness of triptans was estimated with regard to 2-hour response, 2-hour pain-free, recurrence, and any adverse event, using published clinical data. Direct and indirect costs (2010 EUR, societal perspective) and quality-adjusted life-years (QALYs) were evaluated over one acute migraine attack using a decision-tree model. RESULTS: The meta-analysis combined data from fifty-six publications. The highest probability of achieving the primary outcome, "sustained pain-free, no adverse event" (SNAE), was estimated for eletriptan 40 mg (20.9 percent). Sumatriptan 100 mg was the treatment with lowest estimated costs (€20.86), and the incremental cost-effectiveness ratio of eletriptan 40 mg compared with sumatriptan 100 mg was €43.65 per SNAE gained (€19,659 per QALY gained). CONCLUSION: Depending on the decision-maker's willingness-to-pay threshold, either sumatriptan 100 mg or eletriptan 40 mg is likely to be cost-effective.