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Initial Use of Pregabalin, Patterns of Pain-Related. Pharmacotherapy, and Healthcare Resource Use among Older Patients With Fibromyalgia. Mugdha Gore ...
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Initial Use of Pregabalin, Patterns of Pain-Related Pharmacotherapy, and Healthcare Resource Use Among Older Patients With Fibromyalgia Mugdha Gore, PhD, BPharm; Alesia Sadosky, PhD, MPH, MBA; Gergana Zlateva, PhD; and Daniel Clauw, MD

Abstract Objective: To characterize the comorbidities, painrelated pharmacotherapy, and healthcare resource use among older patients with fibromyalgia (FM) newly prescribed pregabalin in clinical practice. Methods: Using the PharMetrics database, patients with FM aged 65 or more years (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) who were newly prescribed pregabalin (index event) on or after July 1, 2007, were identified (N = 98, mean age 72.4 ± 6.4 years; 81.6% female). Prevalence of comorbidities, pharmacotherapy, and healthcare resource use/costs (pharmacy, outpatient, inpatient, total) were examined during the 6-month preindex and postindex periods. Results: Patients had a variety of comorbidities including various disorders generally associated with an older population, such as hypertension (41.8%), diabetes (22.5%), and coronary artery disease (15.3%). On average, patients received 3.3 ± 2.3 pregabalin prescriptions; the average number of days of therapy was 121 ± 88.9. Patients had a high medication burden in both the pre- and postindex periods; opioids were the most commonly prescribed medications (54.1% vs 59.2%); combination therapy was also common, with opioids and antidepressants the most frequent (35% in both periods). Except for the use of selective serotonin reuptake inhibitors, which decreased significantly in the postindex period (24.5% vs 19.4%, P = .0253), there were no changes in use of any of the other medications, including nonsteroidal anti-inflammatory drugs (36.7% vs 32.7%), tramadol (17.4% vs 24.5%), muscle relaxants (18.4% vs 21.4%), tricyclic antidepressants (21.4% vs 18.4%), serotonin and norepinephrine reuptake inhibitors (10.2% vs 12.2%), and anticonvulsants (17.4% vs 21.4%) after initiation of pregabalin therapy. There were decreases in the number of physician office visits and total outpatient visits (both P 65 years old) with FM initiated on pregabalin.

Methods Data Source

Data were obtained from the PharMetrics Patient-Centric Database, which is comprised of adjudicated medical and pharmaceutical claims data from a systematic sample of over 95 commercial managed care health plans throughout the United States (Midwest 34%, Northeast 22%, South 29%, West 15%). This database covers more than 57 million individuals, and includes information on patient demographics and enrollment, inpatient and outpatient diagnoses (ICD-9-CM format [International Classification of Diseases, Ninth Revision, Clinical Modification]), and retail and mail order prescription records. Available data on prescriptions include the National Drug Code numbers, days supply, and quantity dispensed. Medical records for each patient can be linked using a unique encrypted patient identifier (thereby maintaining patient confidentiality) to create a longitudinal record of an individual’s healthcare claims during a specified time period. The database is in compliance with the Health Insurance Portability and Accountability Act of 1996. VOL. 16, No. 5

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Sample Selection

Patients 65 years of age or older who had 2 or more healthcare encounters with an associated diagnosis of FM (ICD-9-CM code 729.1X) on or after January 1, 2006, were selected, and a cohort of patients who were newly prescribed pregabalin (index event) after July 1, 2007, were identified; patients had to be naïve to pregabalin during the 6-month pretreatment period. Reasons for exclusion included missing data for age or sex, or lack of continuous enrollment for a period of 6 months prior to (preindex) and 6 months following (postindex) the date of their first prescription. Measures and Analyses

Basic demographic and clinical characteristics of the patients prescribed pregabalin for FM were determined, including average age, sex distribution, and coprevalence of selected chronic conditions, including mental disorders, sleep disorders, digestive disorders, musculoskeletal pain conditions (eg, arthritis and arthropathies, lumbago, low back pain, osteoarthritis), and neuropathic pain conditions. Comorbidities evaluated were those considered to have significant coprevalence in patients with rheumatic diseases such as cardiovascular-related disorders,11 or to be associated with FM or pain (eg, anxiety, depression, sleep disorders).12,13 The prevalence of comorbidities was determined based on the presence of 2 or more healthcare encounters with an associated diagnosis code for the comorbidity during the 6-month preindex period. ICD-9-CM diagnoses codes used to define comorbidities examined in this study are described in Table 1. Pain-related medication exposure was determined based on the proportion of patients who received 1 or more prescriptions during the pre- and postindex periods for the various medications and medication classes recommended and/or used for the treatment of FM or pain in clinical practice.14-24 These medications included short-acting opioids (SAOs [eg, oxycodone, hydrocodone, morphine sulfate]); long-acting opioids (LAOs [eg, controlled-release oxycodone, transdermal fentanyl]); anticonvulsants other than pregabalin and gabapentin (eg, lamotrigine); TCAs (eg, amitriptyline, desipramine); SSRIs (eg, citalopram, paroxetine); selective serotonin and norepinephrine reuptake inhibitors (SNRIs [eg, duloxetine, venlafaxine]); cyclooxygenase (COX)-2 specific and nonspecific nonsteroidal antiinflammatory drugs (NSAIDs); tramadol; tetracyclic and miscellaneous antidepressants (eg, bupropion, trazodone); topical agents approved for neuropathic pain (eg, capsaicin, lidocaine); topical corticosteroids (eg, betamethasone, desoximetasone); injectables (eg, bupivacaine, lidocaine);

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Report n Table 1. Diagnostic Codes Used to Identify Relevant Comorbidities Comorbidity

ICD-9-CM Diagnosis Codes

General Medical Conditions    Neoplasms

140.X-239.X

   Diabetes

250.XX

   Chronic renal failure

585

   Chronic obstructive pulmonary disease Neuropsychiatric Disorders

491.XX, 492.X, 496

   Depression

296.2X, 296.3X, 300.4, 311

   Anxiety

300.00, 300.5, 300.09, 300.20, 300.22, 300.23, 300.29, 300.3, 308.3

   Bipolar disorder

296.4X, 296.5X, 296.6X, 296.7

   Generalized anxiety disorder

300.02

   Panic disorder

300.01, 300.21

   Posttraumatic stress disorder Migraine and Tension Headache

309.81 346.XX, 307.81

Sleep Disorders    Insomnia/sleep disorders

780.5X, 307.4X, 347.0X, 347.1X, V69.4

   Sleep apnea Fatigue-Related Conditions

780.51, 780.53, 780.57

   Chronic fatigue syndrome

780.71

  Other malaise and fatigue Cardiovascular Disorders

780.79

   Hypertension

401.X

   Hyperlipidemia

272.0, 272.1, 272.2, 272.4

   Coronary heart disease

410.XX-414.XX

   Congestive heart failure

428.0

   Peripheral vascular disease Musculoskeletal Pain Conditions

440.2X, 440.3X, 443.89, 443.9

   Rheumatism, excluding the back

725-728.9, 729.3-729.9

   Arthritis and other arthropathies

711.XX, 712.XX, 713.X, 714.4X, 714.8X, 714.9X, 716.XX, 717.XX, 718.XX, 719.XX

   Back and neck pain, excluding low back pain

720.81, 720.89, 720.9, 721.0, 721.2, 721.5, 721.6, 721.7, 721.8, 721.9, 722.11, 722.30, 722.31, 722.39, 722.4, 722.51, 722.60, 722.80, 722.81, 722.82, 722.90, 722.91, 722.92, 723.X (except 723.4), 724.01, 724.1, 724.5, 724.8, 724.9

   Lumbago

724.2

   Low back pain

720.0, 720.1, 720.2, 721.3, 722.10, 722.32, 722.52, 722.83, 722.93, 724.02, 724.6, 724.7X

  Osteoarthritis

715.XX

   Rheumatoid arthritis

714.0, 714.1, 714.2

  Other Gastrointestinal Conditions

730.00-739.X

   Irritable bowel syndrome

564.1

   Gastroesophageal reflux disease

530.11, 530.81

   Gastritis

535.00 -535.5X

  Other

520.5-530.10, 530.19-530.7, 530.82-534.91, 535.60-537.X, 540.0-543.X, 550.00-553.XX, 555.0-558.X, 560.XX, 562.XX, 564.2-579.X

Neuropathic Pain Conditions

053.1, 250.6, 337.1, 337.2X, 337.9, 344.6, 350.1, 350.2, 353.0, 353.1, 353.6, 353.8, 353.9, 354.0, 354.1, 354.2, 354.3, 354.4, 354.5, 354.8, 354.9, 355.0, 355.1, 355.2, 355.3, 355.4, 355.5, 355.6, 355.71, 355.79, 355.8, 355.9, 357.1, 357.2, 357.3, 357.4, 357.5, 357.6, 357.7, 357.8, 357.9, 721.1, 721.41, 721.42, 721.91, 722.7X, 723.4, 724.3, 724.4, 729.2, Malignant neoplasms (140.XX-172.XX, 174.XX-208.XX) in conjunction with neuropathy 337.2X, 353.0, 353.1, 353.2, 353.3, 353.4, 353.8, 353.9, 354.0, 354.1, 354.2, 354.3, 354.4, 354.5, 354.8, 354.9, 355.0, 355.1, 355.2, 355.3, 355.4, 355.5, 355.6, 355.7X, 355.8, 355.9, 357.3, 357.8, 357.9, 729.2

Signs, Symptoms, and Ill-Defined Conditions    Anxiety-related symptoms

780.4, 785.0, 785.1, 786.01, 786.05, 786.09

   Gastric-related symptoms

787.0, 787.01-787.03, 787.1-787.3, 787.9, 787.91, 787.99

  Other

780.02-780.39, 780.6, 780.8-783.9, 784.1-784.9, 785.2-786.00, 786.02-786.04, 786.06, 786.07, 786.1-786.4, 786.6-786.9, 787.4-787.7, 788.0-788.9, 789.1-796.9, 799.X

ICD-9-CM indicates International Classification of Diseases, Ninth Revision, Clinical Modification.

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Initial Use of Pregabalin, Patterns of Pain-Related Pharmacotherapy, and Healthcare Resource Use triptans and other antimigraines; and attention-deficit/hyperactivity disorder drugs. Additionally, exposure to benzodiazepines, sedatives/hypnotics, and muscle relaxants was evaluated, since these may be used adjunctively to treat pain-related mood and sleep disorders, which are frequently reported in patients with FM. Use of opioid analgesics was examined on an aggregate basis (ie, any opioid) and separately by the type of formulation and duration of action (ie, SAOs and LAOs). Because opioid analgesics are often prescribed and used as rescue pain medications or on an “as needed” basis, evaluation of opioid use was stratified by patients who received 1 or more, only 1 or 2 or more opioid prescriptions in the pre- and postindex periods, respectively. The direct medical costs associated with healthcare resources, including physician office visits, emergency department visits, hospitalizations, and other outpatient services (eg, labs, radiology, imaging), were examined for the preand postindex periods. The average number of prescriptions, days of therapy, and the time (days) between prescription refills were determined. The average daily dose was calculated as strength in milligrams multiplied by the quantity prescribed divided by days supply. Several methods were used to evaluate average daily dose. First, the average daily dose was calculated for the index pregabalin prescription as well as across all pregabalin prescriptions during the followup period. Second, the proportion of patients who received a dose within specific predetermined dose levels was evaluated among patients who received only 1, 2, and 3 or more consecutive prescriptions, respectively. A consecutive prescription was defined as a prescription whose “start date” was no later than 15 days after the “end date” of the previous prescription. Patient adherence was determined based on a surrogate outcome, the medication possession ratio (MPR). The MPR evaluates the persistency of medication availability over time in the form of prescription refills, and has been widely used as a measure of adherence when using administrative claims databases. The MPR was calculated as the total days supply (excluding day supply of last prescription) divided by the total number of days between the first and last prescriptions. Statistics

All study analyses were conducted using the SAS software system, PC version 8.0 (SAS Institute Inc, Cary, NC). Since the same subjects were included in the preand postindex periods (ie, matched pairs), McNemar tests were used to assess the statistical significance of changes in proportions of patients who received the various classes of VOL. 16, No. 5

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study medications between these periods. Wilcoxon signed rank tests were used to calculate the statistical significance of differences between the number of prescriptions patients received for the various study medication classes in the preand postindex periods, and for any differences in costs between these periods. An alpha value 5

56 (57.1)

COX-2 inhibitors, SAOs, LAOs, antidepressants, and anti­ convulsants. Opioids were the most frequently prescribed medication (54.1%), especially SAOs (52.0%), followed by NSAIDs (36.7%). Adjunctive medications including benzodiazepines, muscle relaxants, and sedatives/hypnotics that are often used to treat conditions associated with pain,

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such as depression, anxiety, and insomnia, were prescribed in 20% to 32% of patients. Other than a small but significant decrease in the proportion of patients prescribed SSRIs in the postindex period, from 24.5% to 19.4% (P = .0253), there were no changes in the use of any of the medication classes examined in this study, including opioids.

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Initial Use of Pregabalin, Patterns of Pain-Related Pharmacotherapy, and Healthcare Resource Use n Table 3. Proportions (Percent) of Older Patients With Fibromyalgia Newly Prescribed Pregabalin (N = 98) With >1 Claim for Pain-Related Medications in the Pre- and Postindex Periods Patients, % Medication

Preindex

Postindex

Short-acting opioids

52.0

59.2

.1615

Long-acting opioids

11.2

12.2

.5637

Any opioids

54.1

59.2

.3173

COX-2 inhibitors

12.2

14.3

.4795

Nonselective NSAIDs

27.6

22.5

.2253

Any NSAIDs

36.7

32.7

.3458

SSRIs

24.5

19.4

.0253

SNRIs

10.2

12.2

.5271

Tricyclic antidepressants

21.4

18.4

.2568

Anticonvulsants

17.4

21.4

.4142

Muscle relaxants

18.4

21.4

.4913

Benzodiazepines

29.6

31.6

.6171

Sedative/hypnotics

20.4

21.4

.7389

Tramadol

17.4

24.5

.0896

Miscellaneous agents

Pa

6.1

3.1

.1797

Tetracyclic and miscellaneous antidepressants

17.4

17.4

1.0000

Topical agents approved for NeP

10.2

11.2

.7630

Topical corticosteroids

12.2

7.1

.2253

Injectables

0

0



Attention-deficient/hyperactivity disorder drugs

3.1

3.1

1.0000

Triptans

2.0

1.0

.3173

Other antimigraines

0

0



Corticosteroids

22.5

21.4

.8084

All other medications

98.0

95.9

.4142

COX indicates cyclooxygenase; NeP, neuropathic pain; NSAIDs, nonsteroidal anti-inflammatory drugs; SNRIs, serotonin and norepinephrine reuptake inhibitors; SSRIs, selective serotonin reuptake inhibitors. a McNemar test for difference between pre- and postindex periods.

Multiple medication classes were commonly prescribed, with approximately 80% of patients prescribed 2 or more classes, and more than 30% of patients prescribed 5 or more classes in both the pre- and postindex periods. Overall, there was no difference from the pre- to postindex period in the proportion of patients prescribed multiple medication classes (P = .9096). Similarly, as shown in Table 4, there was no overall difference between the 2 periods in the proportion of patients who were prescribed combination therapies (P = .9608); approximately 54% of patients in both periods were prescribed at least 1 combination. The most frequent combination therapy was antidepressants plus opioids, prescribed to 35% of patients in each period, followed by sedatives/hypnotics plus opioids (16% and 17% for the pre- and postindex periods, respectively). VOL. 16, No. 5

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When medications identified in the APS recommendations were evaluated, there were no changes between the 2 treatment periods in the proportion of patients who received any of these medications (Table 5), the number of prescriptions for these medications, or the days of therapy with these medications (data not shown). Tramadol was the medication prescribed to the greatest proportion of patients during the pretreatment and follow-up periods, 17.4% and 24.5%, respectively. Dosing and Adherence to Pregabalin

The average number of pregabalin prescriptions over the 6-month period was 3.3 ± 2.3, with an average of 121 ± 88.9 days of therapy. The average daily dose of the first pregabalin prescription in the postindex period was 149.7 ± 79.8 mg/

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Report n Table 4. Proportions (Percent) of Older Patients With Fibromyalgia Newly Prescribed Pregabalin (N = 98) Who Received Combination Therapy in the Pre- and Postindex Periods Patients, % Combinations

Preindex

Postindex

   0

46.9

45.9

   1

18.4

20.4

Pa

No. of Combinations

   2

16.3

12.2

   3

12.2

10.2

   4

1.0

7.1

   5

2.0

1.0

   >6 Anticonvulsants + antidepressants TCAs + sedatives/hypnotics

.9608

3.1

3.1

11.2

11.2

1.0000

4.1

5.1

.5637

TCAs + SSRIs

3.1

3.1

1.0000

TCAs + NSAIDs

8.2

7.1

.6547

Benzodiazepines + sedatives/hypnotics

7.1

5.1

.4795

Anticonvulsants + sedatives/hypnotics

7.1

5.1

.5271

34.7

34.7

1.0000

Antidepressants + opioids Muscle relaxants + sedatives/hypnotics Benzodiazepines + NSAIDs Anticonvulsants + antidepressants + opioids

3.1

5.1

.3173

10.2

16.3

.0578

6.1

10.2

.2059

16.3

17.4

.7815

Corticosteroids + anticonvulsants

4.1

8.2

.1573

Miscellaneous + anticonvulsants

3.1

1.0

.1573

Miscellaneous + TCAs

4.1

1.0

.0833 .3173

Sedatives/hypnotics + opioids

Miscellaneous + opioids

5.1

3.1

Antimigraine + anticonvulsants

0

0



Antimigraine + TCAs

0

0



Antimigraine + opioids

0

0



Sedatives/hypnotics + anticonvulsants + TCAs

3.1

2.0

.5637

NSAIDs, nonsteroidal anti-inflammatory drugs; TCAs, tricyclic antidepressants; SSRIs, selective serotonin reuptake inhibitors. a McNemar test for difference between pre- and postindex periods.

day, and the average dose across all prescriptions was 168.9 ± 104.4 mg/day. When dosing was evaluated by consecutive prescriptions, of the patients who received 1 (n = 24), 2 (n = 15), or 3 or more (n = 19) prescriptions, only 8.3%, 13.3%, and 21.1%, respectively, received a dose within the therapeutic range for FM (300-450 mg/day) by their first, second, or third prescription. Patient adherence to pregabalin was high; 63.5% of patients achieved an MPR in excess of 80%, and the average MPR was 78.9% ± 25.2%. The median time between prescription refills was 1 day (interquartile range of –8 to 8 days).

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Resource Use, Nonpharmacologic Therapies, and Costs

Results suggested substantial healthcare resource use in both the pre- and postindex periods. There were no differences between the 2 treatment periods in the proportion of patients using the different categories of healthcare resources (physician office visits, emergency department visits, other outpatient visits, and hospitalizations). Almost all of the study patients (99%) visited a physician at least once during both treatment periods; general/family practitioners and internists were the specialists most frequently consulted (40%-45% of patients), with consultations with rheuma-

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Initial Use of Pregabalin, Patterns of Pain-Related Pharmacotherapy, and Healthcare Resource Use n Table 5. Proportions of Patients Prescribed Pregabalin (N = 98) Who tologists (21%-22%) or neurologists also Had >1 Claim for Select Medications Identified in American Pain Society common (20%-22%) in the pre- and Recommendations for the Treatment of Fibromyalgia5 postindex periods. Chiropractors were Percent consulted by approximately 15% of patients, and less frequent consultations Medication Preindex Postindex Pa were reported with psychiatrists (6%Pregabalin — 100.00 — 8%) and psychologists (1%-2%). Cyclobenzaprine 10.20 13.27 .4386 When physician visits were stratiTramadol 17.35 24.49 .0896 fied by specialty, there were no differFluoxetine 6.12 6.12 1.0000 ences in frequency of visits between the Sertraline 5.10 3.06 .1573 2 treatment periods except for physical Venlafaxine 3.06 2.04 .5637 therapists, which decreased by almost Duloxetine 7.14 10.20 .2568 half, from 21.4% to 12.2% (P = .020). However, significant differences were Gabapentin 13.27 15.31 .6547 observed in the number of physician ofa McNemar test for difference between pre- and postindex periods. fice visits and the total number of outpatient visits, with fewer visits reported in the postindex period (Table 6). When nonpharmacologic therapies identified in the Discussion APS recommendations were evaluated, few patients received these therapies. In the preindex period, theraPrevious burden of illness studies have shown that patients peutic exercises/strength training was only used by 15% with FM are characterized by a high prevalence of comorbid of patients and cognitive behavioral therapy was used by conditions and by a substantial medication burden.23-26 The only 10%, with slight but nonsignificant decreases to 11% current study, which is the first to report on the presence of (P = .285) and 7% (P = .083), respectively, in the post­ comorbidities and patterns of pharmacologic therapy among index period. older patients who had a clinical diagnosis of FM, shows that Total median healthcare costs were $6493 (interquartile the burden in these patients is at least as great as in a younger range $3863-$12,095) and $5607 (interquartile range FM population. $35,901-$12,643) for the pre- and postindex periods, reNot surprisingly, given the age of this population (mean spectively. This difference was not significant (P = .634), 72.4 ± 6.4), multiple comorbidities were common, with the and neither were significant differences observed between presence of 5 or more comorbid conditions reported in more the 2 treatment periods for either the cost of any of the than half of the patients. Although the prevalence of many individual healthcare resource categories or for individual of these conditions was comparable to what has previously medications. been reported in similar types of studies in more general, n Table 6. Health Resource Utilization in the Pre- and Postindex Periods Among Older Patients With Fibromyalgia Newly Prescribed Pregabalin (N = 98) Days, n Preindex

Postindex

Median (Interquartile Range)

Mean

Median (Interquartile Range)

Pa

Resource

Mean

Total outpatient visits

18.8

16.0 (11-25)

16.4

15.0 (10-21)

.009

   Physician office visits

12.0

11.0 (7-15)

10.0

8.5 (6-13)

.001

0.4

0

0.4

0

.086

10.6

8.0 (5-12)

9.9

8.0 (5-12)

.722

1.8

0

1.5

0

.547

  Emergency department visits   Other outpatient visits Hospitalizations (inpatient days) a

Wilcoxon test for difference between pre- and postindex periods.

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Report younger FM populations,23,25 the prevalence of other comorbidities that may be expected in an older population were higher. In particular, the prevalence of diseases such as diabetes, osteoarthritis, and a variety of cardiovascular conditions (eg, hypertension, congestive heart failure, peripheral vascular disease) was 2- to 10-fold higher than reported in younger FM populations.23,25,26 It is also interesting to note that among older individuals, the prevalence of anxiety as well as migraine/tension headaches was lower than reported in the studies of younger populations, consistent with what was observed in an early comparison of young and old patients with FM.8 A substantial medication burden was observed in both treatment periods, with the only significant difference in medication use an observed reduction in SSRIs during the postindex period. However, few patients received the 300- to 450-mg/day dose of pregabalin that is recommended for the management of patients with FM.27 While the low number of patients in this study may preclude a more accurate assessment of changes in medications from the pre- to the postindex periods, the suboptimal dosing of pregabalin may also have contributed to a less than optimal reduction in pain. Despite the high treatment burden, few patients were prescribed the individual medications recommended in the APS guidelines for the treatment of pain related to FM.5 However, some of the recommended medications that were prescribed are contraindicated in an older population, according to the modified Beers criteria.28 In particular, amitriptyline, fluoxetine, and cyclobenzaprine were prescribed to 6% to 14% of these individuals. Opioids were the most frequently prescribed medication, and in particular, there was a high rate of prescription of SAOs, consistent with other studies that have evaluated FM treatment patterns23-25; SAOs are often prescribed and used as rescue pain medications or on an “as needed” basis. Also consistent with other studies,23-25 the most frequent combination therapy was opioids plus antidepressants. This finding is not surprising because depression is also commonly reported in patients with FM and was diagnosed in 15% of the present population. While this combination is not necessarily associated with greater side effects than opioids alone even among older individuals,29 the general recommendation is for the cautious use of opioids in older patients.30 These recommendations are based on age-related decreases in hepatic, renal, and gastrointestinal function that may exacerbate issues of safety and tolerability, as well as on the increased presence of polypharmacy and the occurrence of side effects such as drowsiness, dizziness, and motor imbalance that may have more serious consequences in this population relative to younger individuals.30

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There were few changes in resource use between the treatment periods, with only postindex reductions in the number of physician office visits and the total number of outpatient visits showing significance. The overall health resource costs were similar in the 2 treatment periods, suggesting that addition of pregabalin was cost-neutral. The results of this study are subject to several limitations, including the small sample size. Furthermore, this study was based on individuals with FM who were initiated on pregabalin, and it is possible that the characteristics of these patients may be different from those of FM patients in the database who were not initiated on this therapy. Retrospective database analyses are also potentially prone to errors in coding and recording, which may be especially compounded in FM due to the lack of a specific ICD-9-CM diagnosis code for FM. Importantly, it cannot be ascertained from the available data if the prescriptions for pregabalin, or for any of the other medications evaluated in this study, were prescribed for pain related to FM or for other indications. Nevertheless, the information obtained in this study with regard to which medications are being prescribed in older patients with FM can inform future treatment decisions. An additional consideration is that the prescribing of a particular medication does not necessarily imply that the patient filled the prescription or used the medication. However, it should be noted that patient adherence to pregabalin was high, and the MPRs among patients prescribed pregabalin were generally comparable to those reported in the literature for medications used to treat other chronic conditions such as hypertension, hyperlipidemia, and diabetes.

Conclusion This study confirms the substantial comorbidity and medication burden among patients with FM, and suggests that this burden may be higher in older individuals with this disease. While few differences in resource utilization and treatment patterns were observed between the 6-month periods before and after the initiation of pregabalin therapy, the initiation of pregabalin therapy itself appeared to be cost-neutral. The lack of information on FM in older individuals suggests that the current study is an important step in characterizing the burden and needs of this population. Further evaluation of the characteristics of older patients with FM and the challenges associated with their treatment may not only add to our knowledge of this disease, but can improve management strategies in this fragile population, especially related to reducing polypharmacy.

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Initial Use of Pregabalin, Patterns of Pain-Related Pharmacotherapy, and Healthcare Resource Use Acknowledgment

The authors would like to thank E. Jay Bienen for editorial assistance in the preparation of this manuscript, which was funded by Pfizer, Inc. Author Affiliations: From Avalon Health Solutions, Inc (MG), Philadelphia, PA; Pfizer, Inc.—Global Outcomes Research (AS, GZ), New York, NY; and Department of Anesthesiology (DC), University of Michigan, Ann Arbor, MI. Funding Source: This supplement was funded by Pfizer, Inc. Author Disclosures: Dr Gore is principal consultant at Avalon Health Solutions, Inc, who were paid consultants to Pfizer in connection with the development and execution of both this manuscript and the research it describes. Dr Gore also owns stock in Pfizer. Drs Sadosky and Zlateva are employees of Pfizer and own stock in Pfizer. Dr Clauw was not compensated for his participation in this research or for the preparation of this article. Dr Clauw has performed consulting for Cypress Bioscience, Forest, Lilly, Pfizer, Pierre Fabre, and UCB, and has received research funding support from Forest and Pfizer, Inc.  Authorship Information: Concept and design (MG, AS, GZ, DC); acquisition of data (MG); analysis and interpretation of data (MG, AS, GZ); drafting of the manuscript (MG, AS, DC); critical revision of the manuscript for important intellectual content (MG, AS, GZ, DC); statistical analysis (MG); obtaining funding (MG, AS, GZ); administrative, technical, or logistic support (GZ); and supervision (MG, AS, GZ). Address correspondence to: Mugdha Gore, PhD, BPharm, Avalon Health Solutions, Inc, 1518 Walnut St, Ste 1507, Philadelphia, PA 19102. E-mail: [email protected].

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