Sumatriptan treatment for migraine in a health maintenance organization: Economic, humanistic, and clinical outcomes

Sumatriptan treatment for migraine in a health maintenance organization: Economic, humanistic, and clinical outcomes

CLINICAL THERAPEUTICSWOL. Sumatriptan Maintenance and Clinical 2 1, NO. 1, 1999 Treatment for Migraine in a Health Organization: Economic, Humanis...

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CLINICAL

THERAPEUTICSWOL.

Sumatriptan Maintenance and Clinical

2 1, NO. 1, 1999

Treatment for Migraine in a Health Organization: Economic, Humanistic, Outcomes

Jeffrey A. Cohen, MD, I,2 Donna Beall, PharmD,3Arne Beck, PhD,’ Julia Raw&p, RPh,’ David W. Miller, PhD,4 Bill Clements, MS,4 D. Gayla Pait, MS,4 and Alice Batenhorst, PharmD4 ‘Kaiser Permanente, 2Departmentof Neurology, University qf Colorado Health Sciences Center; Denvel; Colorado, 3Pharmacy Practice, University of Montana, Missoula, Montana, and 4Glaxo WellcomeInc., ResearchTriangle Park, North Carolina

ABSTRACT This study was undertaken to assessthe impact of 12 months of sumatriptantherapy (6 mg subcutaneously) for migraine on health care use, health-related quality of life, productivity, patient satisfaction with the medication, and clinical efficacy in a health maintenance organization (HMO). One hundred forty-eight patients received open-label sumatriptan for 12 months for the treatment of migraine. Medical records were reviewed to obtain information on the frequency of migrainerelated health care use during the 12 months before and during sumatriptan treatment. Patients completed questionnaires on their productivity at work, health-related quality of life, and satisfaction with medication at baselineand after 3, 6, and 12 months of sumatriptan treatment. For each migraine, patientsrecorded 190

pain severity scoresbefore and after taking sumatriptanand the time betweendosing and onset of meaningful relief. Sumatriptan was associated with significant reductions in migraine-relateduse of general outpatient services, telephone calls, urgent care services, and emergency department visits (P < 0.05); a significant increase in the use of pharmacy services (P < 0.05); and significant and sustained improvementsin health-relatedquality-oflife scores compared with baseline (P < 0.001). Patientslost significantly lesstime from work and were significantly more satisfied with sumatriptan comparedwith their usual therapy (P < 0.05). Two hours after dosing, 81% of patients experienced reduction of moderate or severe pain to mild or no pain, and 90% of all patients experiencedmeaningful relief of pain. The use of sumatriptan for 12 months in an HMO was associatedwith reductions in 0149.2918/99/$19.00

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health care use and improved healthrelated quality of life, productivity, and patient satisfaction with medication. Key words: sumatriptan, migraine, health care use, health-related quality of life, HMO. INTRODUCTION Most patients who seek medical treatment for headache visit general or family practitioners.’ These primary care providers are consulted more than 9 million times per year for headache.2 Migraine, estimated to afflict over 17% of women and 6% of men in the United States,’ is associated with substantial clinical, humanistic, and economic impacts. 3-8 Uncontrolled migraine attacks, in which bouts of headache lasting up to 3 days may be accompanied by nausea, photophobia, and phonophobia, impair general well-being and disrupt social functioning both during acute attacks and in the intervals between attacks.3,9 The debilitation associated with migraine has economic consequences: one US study estimated the direct costs of 648 migraineurs’ medical care at over $500,000 annually,7 and indirect migraine-associated costs due to lost workplace productivity were estimated to range between $1.4 and $17.2 billion per year.5,7 In a study of 2672 patients enrolled in a health maintenance organization (HMO), total medical and pharmacy claims were 62% higher in those with a diagnosis of migraine than in those with no diagnosis of migraine.s Advances in migraine research over the last decade have yielded therapies that effectively reduce acute migraine symptoms. Sumatriptan, a serotonin-1 agonist, administered subcutaneously, orally, or intranasally, is effective in alleviating the pain and associated symptoms of the acute migraine attack. *O-l3 Moderate or severe

predose pain is reduced to mild or no pain by 2 hours after dosing in approximately 80% of patients treated with the subcutaneous form and 63% of patients treated with the nasal form, and by 4 hours after dosing in 65% to 78% of patients treated with thegral [email protected] Although the clinical efficacy of sumatriptan is well documented, health care decision-makers, particularly in the managed care environment, are also interested in data that will help them assess the association between sumatriptan therapy and patients’ use of health care resources, health-related quality of life, and productivity. To assess these associations, it is often necessary to observe patients in a naturalistic setting, that is, outside the confines of a controlled clinical trial. The present study was designed to observe the effects of 12 months of subcutaneous sumatriptan therapy on health care resource use by group-model HMO members. In addition to health resource use, healthrelated quality of life, productivity, patient satisfaction with medication, and clinical efficacy were assessed throughout the sumatriptan treatment period. The study data on health care use and healthrelated quality of life for the first 6 months of sumatriptan treatment have been published elsewhere.14 PATIENTS

AND METHODS

Patients Men or women 218 years of age who had been members of the group-model HMO for at least 1 year were eligible for the study. Patients were identified by health care providers within the health plan (eg, neurologists, primary care providers, nursing staff, and clinical phar191

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macists) and were referred to study staff as potential study candidates. Patients were screenedby telephone and, if qualified, were invited for a screening clinic visit. Patients were eligible if they had at least a l-year history of migraine with or without aura diagnosed according to International Headache Society criteria,t5 with a recent history of approximately 2 to 6 moderate or severe migraine attacks per month, and if they had had at least 2 visits during the past year for the treatment or assessmentof migraine. Patients with basilar or hemiplegic migraine or patients with known ischemic heart disease, Prinzmetal’s angina, or symptoms or signs consistent with ischemic heart disease were excluded. Pregnant or breastfeeding women or women not using adequate contraception were also excluded. All patients provided written informed consent. Methods The protocol for this study was approved by the institutional review board for the study site. An open-label design was chosen in collaboration with the HMO to simulate conditions under which the health plan would introduce new therapies to its members. Migraine care was provided by patients’ regular HMO physicians (general practitioner or specialist). Patients were seen by the study staff at baseline and at 3, 6, and 12 months. Patientscould treat an unlimited number of mild, moderate, or severe migraine attacks for up to 12 months with subcutaneoussumatriptan(6 mg), which they selfadministeredat homeusingan autoinjector. They were instructed to use subcutaneous sumatriptan as the first treatment for migraine. Medications containing ergotamine 192

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were prohibited 24 hours before or after dosingwith sumatriptan. Measurementof Health Care Use Patients’ medical records for the 12 months before and 12 months after study entry were abstracted to determine the number of migraine-related general outpatient visits, telephonecalls, imaging services, emergency department visits (excluding urgent care), urgent care visits, and hospitalizations. Patients’ useof each of the resourceswas compared between the 12 monthsbefore and 12 months after initiation of treatment using the Wilcoxon signed rank test. Medians were reported for health care use,becausedata were not normally distributed and nonparametric tests were applied. Use of pharmacy services (number of prescriptions) was determined from the HMO’s pharmacy database.Sumatriptan use, which was included in the determination of pharmacy services, was determined by standardizing sumatriptan dispensing quantities according to HMO guidelines. (Study-related sumatriptan prescriptions were not included in the HMO pharmacy records because sumatriptan was dispensedby the study investigator.) The HMO’s standard practice is to provide patients with a 60-day supply of medication through its pharmacies.The average number of sumatriptan kits (2 injections) used per patient over 60 days wasdeterminedto be 4.3 kits for the treatment period. Thus every 4.3 kits usedwas considered 1 sumatriptan prescription (or the equivalent of a 60-day supply). Measurementof Quality of Life At clinic visits at baselineand at 3, 6, and 12 months into the treatment period, patients completedthe Medical Outcomes

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Study [email protected] (SF-36) Health Survey and the Migraine-Specific Quality of Life (MSQ) Questionnaire0 (Version 1.0, copyrighted 1992 by Glaxo Wellcome Inc., Research Triangle Park, North Carolina). The 36-item SF-36, a general health status questionnaire that has demonstrated validity and reliability in a variety of patient populations,16~17 measures 8 aspects of health-related quality of life: physical functioning, limitations in role functioning due to physical health, bodily pain, general health perceptions, vitality, social functioning, limitations in role functioning due to emotional health, and general mental health. The MSQ, a 16-item diseasespecific instrument, assesses aspects of health believed to be particularly affected by migraine.18T19 Three dimensions are measured: role-function restrictive (the degree to which performance of normal activities is restricted or limited by migraine); role-function preventive (the degree to which performance of normal activities is prevented or interrupted by migraine); and emotional function (the emotional effects of migraine). For example, typical questions address migraine-associated difftculties in attending social activities (rolefunction restrictive) or the degree to which a migraineur feels that his or her migraines create burdens for others (emotional function). The MSQ has shown evidence of reliability and validity in migraine sufferers participating in clinical trials18919and in an HMO population with migraine.20 Data analysis was conducted according to procedures described in previous publications.21s22 Each of the 8 SF-36 dimensions and the 3 MSQ dimensions was scored separately and transformed onto a scale ranging from 0 (least favorable score) to 100 (most favorable score). If an SF-36 item was not answered, the item score for

that patient was replaced with the average dimension score computed without the missing item. If more than half of the items within a dimension were missing for a patient, the entire dimension was treated as missing for that visit. If more than 1 item was missing on the MSQ, the score for that dimension was considered to be missing for that visit. Linear regression analyses were used to produce adjusted scores for the SF-36 (scores adjusted for age; sex; race; baseline scores; and selected comorbidities, including arthritis, chronic obstructive pulmonary disease, back pain, hypertension, gastrointestinal distress, clinical depression, and urinary tract infection). Contrast statements were used to generate pairwise comparisons between baseline scores and 3-, 6-, or 12-month scores, when appropriate. Measurement of Productivity At clinic visits at baseline and at 3, 6, and 12 months into the treatment period, patients completed questionnaires assessing the effects of migraine on their productivity at work. Patients were asked to recall, for the past 3 months, the average number of days missed from work due to migraine, the average number of days worked with migraine symptoms, the average percentage of effectiveness while working with migraine symptoms, the average number of hours work was affected during a typical migraine, and the average number of days work was affected during a typical migraine. Repeated-measures analyses of variance (ANOVAs) were used to compare baseline productivity data with that at 3, 6, and 12 months. Measurement of Patient Satisfaction At clinic visits at baseline and at 3, 6, and 12 months into the treatment period, 193

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patients completed questionnairesthat included items measuring their satisfaction with medication over the preceding 4 weeks.Six items assessed patient satisfaction on the dimensionsof how well medication worked, how easy medication was to take, how quickly medication worked, number of dosesneededto achieve relief, effectiveness of medication at relieving migraine pain, and effectivenessat relieving other migraine symptoms. For each item, patients’ satisfaction was scored using a 5-point scale: 1 = very satisfied; 2 = somewhatsatisfied; 3 = neutral; 4 = somewhat dissatisfied; and 5 = very dissatisfied. The latter 2 satisfaction items contained 2 additional response categories: “did not have a migraine in the last 4 weeks” and “did not take sumatriptan in the last 4 weeks.” For theseitems, data for patientswho hadnot had amigraineor taken sumatriptanin the past4 weekswere setto missingand the responseimputed from the nearest completed observation. We calculated the percentageof patients rating sumatriptan or usual therapy at baseline in each responsecategory. Mean satisfaction scoresat baselinewerecomparedwith those obtained 3, 6, and 12 months into the sumatriptan phase using repeated-measures ANOVAs. In addition, at eachvisit, the distribution of patients’ scores across the 5-point scalewas calculatedfor eachitem. Clinical Measurements For eachmigraine,patientsrecordedin a diary the severity of migraine pain (none, mild, moderate,or severe)immediately before and 2 hours after dosing. They also recorded the time from dosing to patientdefinedmeaningfulrelief andany useof additional medicationto treat their migraine. The primary clinical efficacy measure was the percentage of patients acrossat194

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tacks achieving headacherelief, defined asthe reduction of moderateor severemigraine pain to mild or no pain 2 hours after dosing. In addition, we calculated the percentage of patients across attacks achieving complete relief, defined as the reduction of moderate or severe migraine pain to no pain 2 hours after dosing and the percentage of patients acrossattacks achieving meaningful relief of mild, moderate, or severepain 2 hours after dosing. These across-attack measureswere tabulated for the 12 months of sumatriptan therapy using survey logistic regression methodology. Patients were considered treatment failures for a given attack if additional treatment was used during the 2 hours after taking sumatriptan. Only attacks initially treated with sumatriptan were included. In addition to examining the percentages of patients across attacks achieving relief, complete relief, and meaningful relief, we determined the meanpercentages of attacks per patient for which thesecriteria were achieved. For patients with migraine relief, headacherecurrence wasdetermined post hoc by examining repeat doses of sumatriptan within the 2- to 24-hour period after the initial dose. RESULTS

Patient Characteristics One hundred fifty patients(the majority identified by primary careprovidersor clinical pharmacy staff) were enrolled in the study, and 149 took at least 1 doseof sumatriptan. Assessablepharmacoeconomic data were obtained for 148 of these 149 patients. Most patients were women and mostwere white. Fifty-six percent(83/149) of patientshad not usedsumatriptanbefore

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entry into the study (Table I). Seventy-eight percent of patients had usedfewer than 2 dosesof sumatriptanbefore the study. The meannumberof dosesof sumatriptantaken by patients who had received sumatriptan prior to enrollment was5.1 (range, 1 to 24 doses). Migraine prophylactic medications were taken by 87 (58%) of the 149 patients who had taken at least 1 doseof sumatriptan. The most frequently usedprophylactic medications were amitriptyline (34/149, 23%), verapamil (26/149, 17%), propranolol (18/149, 12%), and sodium valproate (16049, 11%). (A patient could have used more than one prophylactic medication during the study.) The most commonly reported medications (>lO% of patients) taken for acute migraine before the study are summarizedin Table II. During the 12 months before study initiation, general practitioners were

more likely than neurologists to have provided care to these patients for a migraine-related visit (general practitioners, 372 visits; neurologists, 219 visits) or any visit (general practitioners, 784 visits; neurologists, 228 visits). During the study period, general practitioners and neurologists were equally likely to have provided care for a migraine-related visit (general practitioners, 97 visits; neurologists, 101 visits), and general practitioners were more likely than neurologists to have provided care for any visit (general practitioners, 444 visits; neurologists, 110 visits). Health Care Use Sumatriptanwas associatedwith significant sustainedreductions compared with the 12-month usual-therapy period in migraine-relatedgeneraloutpatient visits, ur-

Table I. Demographic and patient characteristicsof 149 patients at baseline. Mean age (y) Range Sex, no. (%) Female Male Race, no. (%) White Hispanic Black Other Oriental/Asian Migraine type, no. (%) Without aura With aura With and without aura Data not available Prior treatment with sumatriptan, no. (%) No Yes

43.6 18-65 140 (94) 9 (6) 135 8 3 3 0

(91) (5) (2) (2) (0)

107 (72) 10 (7) 30 (20)

2 (1) 83 (56)

66 (44)

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Table II. Medications other than sumatriptan taken for acute migraine before study enrollment. Medication

No. (%) of Patients

Ibuprofen Acetaminophen Meperidine hydrochloride Hydroxyzine pamoate Butalbital Promethazine hydrochloride Isometh+dichlor+acetamino Prochlorperazine Isometh+dichlor+acetamino cate + dichloralphenazone

52 (35) 44 33 24 23 23 22

(30) (22) (16) (15) (15)

(15) 18 (12)

= isometheptene + acetaminophen.

mu-

gent care visits, emergency department visits, and telephone calls (P < 0.05) and with significant increases in the use of migrainerelated pharmacy services (P < 0.05) (Table III). The frequency of hospitalizations and use of imaging services was not significantly different between the sumatriptan and usual-therapy periods (Table III).

Quality of Life Scores on 7 of the 8 dimensions of the SF-36 Health Survey were significantly higher after 3, 6, and 12 months of sumatriptan therapy compared with baseline scores (P < 0.05) (Figure 1). Except for general health perceptions at 3, 6, and 12 months, vitality at 3 months, and mental health at 3 and 6 months, all these statistically significant changes also represented clinically significant improvements (>5-point change in score).16 Scores on each of the 3 MSQ dimensions were also significantly higher after 3, 6, and 12 months of sumatriptan therapy compared with baseline scores (P < 0.001) (Figure 2). Productivity All mean productivity assessments were significantly more favorable for sumatriptan after 3, 6, and 12 months of treatment compared with usual therapy (P < 0.05) (Table IV).

Table III. Median number of migraine-related and total services used per year per patient during the 12 months before study entry and the 12 months after study entry. Service Outpatient visits* Telephone calls Pharmacy Imaging services Emergency department visits Urgent care visits Hospitalizations

No. of Patients

12 Months After Study Entry

114 110 115

3.0

1.o+

6.0

2.01

6.0

9.6+

35

1.0

0.0

52 54

1.0 2.0

o.o+ o.o+

0

0.0

0.0

*Physician visits excluding urgent care. +P < 0.05 versus 12 months before study entry, Wilcoxon

196

12 Months Before Study Entry

signed rank test.

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-Baseline -.+-- 3 months - l - 6 months 12 months

aoe 708 ClJ 60s Q, 50H 403020

I

PF

I

RP*

I

BP*

I

GH*

I

VT*

I

SF*

I

RE*

I

MH*

Figure 1. Mean scoreson the 8 dimensionsof the Medical OutcomesStudy Short-Form-36 Health Survey at baselineand after 3, 6, and 12 months of sumatriptantherapy, calculated on a scale from 0 (least favorable) to 100 (most favorable). PF = physical functioning; RP = role-physical (limitations in role functioning due to physical health); BP = bodily pain; GH = general health perceptions; VT = vitality; SF = social functioning; RE = role-emotional (limitations in role functioning due to emotional health); MH = general mental health. *P c 0.05 versus baseline, repeated-measures analysis of variance. Patient Satisfaction Mean satisfaction scores were significantly (P < 0.05) more favorable for sumatriptan after 3,6, and 12 monthsof treatment comparedwith usualtherapy on 5 of the 6 satisfactionitems: how well medication worked, how fast medication worked, number of dosesneededto achieve relief, effectivenessof medicationat relieving migraine pain, and effectiveness at relieving other migraine symptoms(Table IV). Differences between sumatriptan and usual therapy on the item “how easy medication is to take” were not statistically significant (Table IV). The percentages of patients reporting that they were very satisfied with suma-

triptan after 12 months of therapy or with usual therapy on the above dimensions were 70% (103/148) and 11% (16/148), respectively, for how well medication worked; 74% (110/148) and 10% (lY148) for how fast medication worked; 57% (84/147) and 14% (21/147) for number of doses needed to achieve relief; 59% (87/148) and 10% (14/148) for effectivenessat relieving migraine pain; and 60% (88/148) and 11% (16/148) for effectivenessat relieving other migrainesymptoms. Clinical Emacy Across all attacks, 90% (133/148) of patients experienced meaningful relief of mild, moderate, or severe pain within 2 197

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THERAPEUTICS”

loo-

Role-Restrictive

Role-Preventive

3 months

Emotional

2. Mean scores on the 3 dimensions of the Migraine-Specific Quality of Life Questionnaire at baseline and after 3, 6, and 12 months of sumatriptan therapy, calculated on a scale from 0 (least favorable) to 100 (most favorable). *P < 0.001 versus baseline, repeated-measures analysis of variance.

Table IV. Mean productivity and patient satisfaction 12 months of sumatriptan therapy.

Baseline Productivity No. of days missed No. of days worked with symptoms Percentage of effectiveness No. of hours of work affected No. of days of work affected Satisfaction How well it worked How easy it was to take How fast it worked No. of doses for relief Effectiveness against migraine pain Effectiveness for relief of other symptoms

scores* at baseline

3 Months

and after 3, 6, and

Duration of Therapy 6 Months 12 Months

2.87 10.80 58.5 7.83 2.05

0.84’ 6.68: 65.0’ 4.70’ 1.50’

0.87+ 6.36+ 66.4’ 5.02+ 1.67’

0.86’ 5.27’ 66.9’ 5.25’ 1.56’

3.03 1.96 3.39 3.41 3.53 3.54

1.46+ 1.82 1.53+ 1.80+ 1.64+

1.451 1.91 1.58f 1.89: 1.76+ 1.76+

1.53+ 1.97 1.47+ 1.951 1.67+ 1.671

*Responses were scored as I = very satisfied, 2 = somewhat satisfied, or 5 = very dissatisfied. ‘I’ < 0.05 versus baseline, repeated-measures analysis of variance.

198

Baseline

0

n 6 months n l12 months

80.

Figure

0

1.70+ 3 = neutral,

4 = somewhat

dissatisfied,

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hours after dosing. Across moderate or severe attacks, 81% (120/148) of patients experienced relief (reduction of moderate or severe pain to mild or no pain) within 2 hours after dosing, and 57% (84/148) experienced complete relief. Ninety-three percent of patients reported meaningful relief 24 hours after the initial dose. Twenty percent of patients used a second dose of sumatriptan after documented headache relief within 2 to 24 hours of the initial dose. The per-patient percentagesof attacks during which the patient experienced relief and complete relief 2 hours postdose were 79% (117048) and 53% (78/148), respectively. The per-patient percentage of attacks during which the patient experienced meaningful relief within 2 hours was 89% (131/148). DISCUSSION AND CONCLUSIONS The results of this study demonstratethat the use of sumatriptan for effective acute control of migraine attacks in an HMO setting was associatedwith reducedhealth care use and sustainedimprovements in health-related quality of life, productivity, and patient satisfaction over a 12-month period. The frequency of migraine-related use of general outpatient services, telephone calls, urgent care services, and emergency department visits decreased during the 12 months of sumatriptantherapy compared with the 12 months preceding study entry. Interim analysisof the dataI revealed that reductions in health care use became evident as early as 3 months after initiation of sumatriptan treatment. These data suggestingthat effective migraine managementreducesthe frequency of medical consultationsare especially germane to primary care pro-

viders, the physicians most frequently consulted for headache.1 These data are consistentwith a report by Greiner and Addy2” of a study conducted in a group-modelHMO. The number of migraine-related office visits decreasedduring the year after sumatriptan wasaddedto the formulary comparedwith the year before. In contrast, Streator and Shearer24 reported that the number of emergency department and physician office visits were higher in an independentpractice-association HMO during the 6 months after sumatriptan was introduced onto the marketplacecomparedwith the 6 months before. The reasonsfor the discrepancy between the results of Streator and Shearerand thoseof the presentstudy and the study by Greiner andAddy are unclear. The increasein the numberof health care visits in the independent-practiceassociationHMO may be partly attributed to patients’ awarenessof the availability of a new therapy for migraine. In addition, the increasein the number of health care visits reportedby Streator and Shearermay reflect physicians’ cautious approach to the use of a new injectable product. The use of migraine-related pharmacy servicesincreasedslightly during sumatriptan treatmentin this study, a resultprobably attributableto patients’free accessto sumatriptan during the study period. The increaseduseof pharmacyservicesmay have been offset by the reduction in generaloutpatient, urgent care, and emergencydepartment visits. More recently, Legg et al25reportedthat while monthly drug expenditures increased,total migraine healthcare expenditures were 41% lower after initiation of sumatriptanand the cost-effectivenessratio was 47% more favorable. This possibility warrants further investigation, as do other economicimplicationsof thesedata. 199

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The health-related quality-of-life data complement the health care use data by demonstrating that the benefits of sumatriptan treatment are manifested in terms that are meaningful to the patient. Statistically significant improvements relative to pre-sumatriptan baseline values in health-related quality of life occurred within 3 months after initiation of sumatriptan treatment in all MSQ dimensions and in 7 of 8 SF-36 dimensions,and these improvements continued throughout the 12-month study period. Across the entire study period, scores on the role-physical (limitations in role functioning due to physical health), bodily pain, social functioning, and role-emotional (limitations in role functioning due to emotional health) dimensionswere both clinically and significantly improved compared with presumatriptan baseline values. Healthrelated quality-of-life scoreswere similar after 3, 6, and 12 months of treatment, a result suggesting that appreciable levels of improvement in health-related quality of life are achieved early (within 3 months of treatment initiation) and maintained over the course of sumatriptan therapy. Similar improvements in health-related quality of life measuredon the SF-36 were observed 6 to 9 months after sumatriptan was initially prescribed to 147 patients with migraine who were treated at the Cleveland Clinic HeadacheCenter.26The improvements that are seenin the physical, emotional, and social aspects of health-related quality of life may be partially attributable to patients’ realization, as they gain experience with sumatriptan, that they can effectively managetheir migraine without compromising their overall functional ability. Sumatriptan may restore a senseof control over an intermittent and unpredictable diseasestate. 200

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The results of another study22employing the SF-36 Health Survey and the MSQ suggest that sumatriptan-associated improvements in health-related quality of life are maintained for at least 2 years. In that study of 344 patients, 3 SF-36 Health Survey dimensions and all MSQ dimensionswere significantly improved during 24 months of subcutaneoussumatriptan treatment compared with pre-sumatriptan baselinevalues. It should be noted that the construct “health-related quality of life” encompassespatients’ overall functional status, well-being, and perceived health.‘6x27Accordingly, health-related quality of life measuressuch asthe SF-36 and the MSQ reflect the global effects of disease on daily well-being and functioning rather than the acute effects of disease symptoms. In the case of migraine, the acute symptomatic impact of the diseaseis just one of the componentsaffecting the measurementof health-related quality of life. Complementingthe health-relatedquality-of-life results,data from this study suggest that sumatriptan therapy also has a positive effect on patients’ productivity. Patientsmissedfewer days of work due to migraine, worked fewer days with migraine symptoms,and had fewer hours and days of work affected by migraine during sumatriptan treatment compared with baseline. Thesedata are consistentwith results of other studies, including a doublemasked,placebo-controlledstudy with sumatriptan injection, in which patients reported an approximate 50% reduction in time lost from work across their work shifts.21,23.28 Eighty-three percent of 160 group-model HMO patients who had used sumatriptan during the 6 months after it was added to the formulary also reported that they missedfewer days of work due to

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migraine.23 In another study in which 43 HMO members used sumatriptan for 6 months for the treatment of migraine, the amount of lost workplace productivity and nonworkplace activity time declined by 35%.*l The determinantsof lost workplace productivity and nonworkplace activity time-time missedfrom work dueto symptoms, time worked with symptoms, and time normal activities were carried on with symptoms-were each lower during 6 monthsof sumatriptantherapy than during 12 to 18 weeks of patients’ usual therapy. Finally, the availability of sumatriptanfor migraine treatmentin an independentpractice associationresultedin improved work productivity, with a benefit-to-cost ratio of 10.1 . .29Thesedata21*23,24 and data from the presentstudy offer strongevidence that sumatriptan counteracts the detrimental effects of migraine on daily functioning, both at work and at home. Consistent with the quality-of-life and health care use data, patient satisfaction ratings demonstrated that patients were very satisfied with the efficacy and time to onset of action of sumatriptan in the present study. During sumatriptan treatment, more than two thirds of patients indicated that they were very satisfied with how well and how fast their medication worked. In contrast, 11% and 10% of patients were very satisfied with how well and how fast, respectively, their usual medication worked at baseline. The patient satisfaction data suggestthat sumatriptan was an effective, well-received alternative to patients’ usual therapy. In fact, most patients experienced headacherelief within 2 hours of taking sumatriptan, and headacherelief was experienced in the majority of attacks per patient-effects observed regardless of whether the 4-point pain scaleor patient-

defined meaningful relief was used as a measure.More than 90% of patients experiencedmeaningful relief within 2 hours of the initial dose, and only 20% of patients used a second dose of sumatriptan within 2 to 24 hours of the initial dose. These clinical efficacy data corroborate those from placebo-controlled, doublemaskedstudiesin which subcutaneoussumatriptan alleviated headacheand associated migraine symptoms, such as nausea, photophobia, and phonophobia, in 70% to 80% of patients, compared with 30% to 40% with placebo.**J3 Onset of relief in double-maskedtrials occurred as early as 10 minutes after dosing.12x13 Recurrence rates of 17% to 39% have been reported in other studies.30s31 A recent publication by Sheftell et a13*reported lower recurrence ratesin migraineurswho had shorter time to treatment or complete relief. Patients in the present study were allowed to treat mild, moderate,or severeattacks and had unrestricted access to sumatriptan. The low recurrence rate reported in this study may be the result of improved treatment access. Becausethe presentstudy did not include a placebo control group, the effects on the study results of participating in a clinical trial cannot be distinguishedfrom the effects of the study drug. It is possiblethat patients’participation in the study increased their accessto treatment, migraine knowledge, and awarenessof appropriate migraine treatment.This awarenessmay have resultedin better managementof headaches and less disability, thereby reducing the number of generaloffice visits for ongoing migraine care. Nevertheless, the consistency of the clinical andhealth-relatedquality-of-life data reported in this study with the results of other studies4J2,‘3,22 (some placebo-controlled)supportsthe contention 201

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that the improvements observed in this study result from sumatriptan treatment. The finding that improvements were maintained through at least 12 months of treatment also lends support to this contention. In this context, it is important to note that the design of this study simulates the changes that HMO members experience when new migraine treatment opportunities are introduced into a managed care setting. Hence, despite the lack of a concurrent control group, these findings may be relevant to similar managed care organizations and patient populations. Health care professionalsmust consider the economicand humanisticaswell asthe clinical impact of their treatment decisions.33Physicians should understandthe effects of various migraine therapies on both clinical end points and extraclinical variables such as health care use, productivity, and health-relatedquality of life. The data from this study give a comprehensive picture of the effects on thesevariables of 12 monthsof treatment with subcutaneous sumatriptan. Consideredin the context of other data, our results indicate that sumatriptan is an effective treatment that counters the detrimental clinical, humanistic, and economic effects of migraine. ACKNOWLEDGMENTS This research was supported by Glaxo Wellcome Inc., Research Triangle Park, North Carolina. This work was previously presentedat the 48th Annual Meeting of the American Academy of Neurology, March 23-30, 1996, San Francisco, California. The authors acknowledge the contributions of Paul Meisner, PharmD; Jamie Blose, PharmD; and Mary Boshkoff. 202

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