Evaluation of healthcare resource utilization and costs in employees with pain associated with diabetic peripheral neuropathy treated with pregabalin or duloxetine

Figures & data

Table 1.  Medications used for managing painful DPN*.

Medication class	Generic name
Non-opioid analgesics (‘NSAIDS’ – Rx only)	Celecoxib, diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac tromethamine, mefenamic acid, meloxicam, nabumetone, naproxen, naproxen sodium, oxaprozin, piroxicam, sulindac, tolmetin sodium, salsalate
Opioid analgesics	Strong opioids: Alfentanil, buprenorphine, fentanyl, hydromorphone, levorphanol tartrate, meperidine, methadone, morphine sulphate, oxycodone, oxymorphone, remifentanil Weak opioids: Butorphanol, codeine, dihydrocodeine, hydrocodone, nalbuphine, pentazocine, propoxyphene, tramadol, and combinations (with acetaminophen, aspirin, etc.)
Anticonvulsants	1st generation: Carbamazepine, divalproex, ethosuximide, phenytoin, primidone, valproate sodium, valproic acid 2nd generation: Gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, zonisamide
Antidepressants	Tricyclics: Amitriptyline and its combinations, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, trimipramine Selective serotonin reuptake inhibitors (SSRIs): Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline Serotonin norepinephrine reuptake inhibitors (SNRIs): Duloxetine, desvenlafaxine, nefazodone, venlafaxine Other: Bupropion, isocarboxazid, maprotiline, mirtazapine, phenelzine, selegiline, tranylcypromine, trazodone
Anesthetics	Lidocaine patch (Lidoderm)

*Only oral and transdermal (patch) medications were included.

Table 2.  Sample size attrition table.

Attrition criterion	Sample
Diabetic peripheral neuropathy diagnosis 4/1/2006–6/  30/2008	160,679
Treated for pain within 60 days on or after DPN diagnosis	53,120
Six months of continuous eligibility both pre- and post-index	37,718
No epilepsy, postherpetic neuralgia, transplant surgery, cancer, or fibromyalgia	32,705
Less than 90 total days in a long-term care facility pre- or post-index	32,633
No pregnancy pre- or post-index	32,496
Age 18–64 years at index	32,468
No pregabalin or duloxetine pre-index	28,060
Employees only (no spouses or dependents)	17,727
Pregabalin index medication before matching*	1,576
Duloxetine index medication before matching*	479
Pregabalin patients after matching	473
Duloxetine patients after matching	473

*Patients in the matching pool met all inclusion and exclusion criteria (index dates were reset to the first pregabalin or duloxetine prescription claim in the index period).

Table 3.  Baseline patient demographic and clinical characteristics.

Characteristic	Pregabalin		Duloxetine		p-value
	n/mean	%/SD	n/mean	%/SD
Number of patients	473	100.0%	473	100.0%
Age, in years	53.6	7.0	53.5	7.4	0.864
Gender					0.268
Male	242	51.2%	259	54.8%
Female	231	48.8%	214	45.2%
Geographic region					0.649
Northeast	42	8.9%	38	8.0%
North Central	103	21.8%	110	23.3%
South	247	52.2%	244	51.6%
West	81	17.1%	79	16.7%
Other	0	0.0%	2	0.4%
Insurance plan type					0.941
Comprehensive	32	6.8%	33	7.0%
Health maintenance org.	79	16.7%	86	18.2%
Point-of-service	50	10.6%	51	10.8%
Preferred provider org.	280	59.2%	274	57.9%
Other	32	6.8%	29	6.1%
Deyo–Charlson Comorbidity Index	2.8	1.5	2.8	1.5	0.601
Select pre-index comorbidities
Diabetes type 1	64	13.5%	71	15.0%	0.515
Diabetes type 2	373	78.9%	367	77.6%	0.636
Other diabetes complications	149	31.5%	141	29.8%	0.573
Hypertension	160	33.8%	155	32.8%	0.730
Dyslipidemia	87	18.4%	92	19.5%	0.678
Musculoskeletal pain	236	49.9%	224	47.4%	0.435
Back pain with neuropathic involvement	44	9.3%	39	8.2%	0.566
Other back pain	76	16.1%	79	16.7%	0.792
Neck pain with neuropathic involvement	11	2.3%	17	3.6%	0.250
Other neck pain (spinal)	41	8.7%	36	7.6%	0.552
Arthritis	62	13.1%	65	13.7%	0.775
Causalgia and other painful neuropathies	62	13.1%	69	14.6%	0.510
Anxiety	103	21.8%	104	22.0%	0.937
Depression	37	7.8%	41	8.7%	0.636
Sleep disorders	45	9.5%	51	10.8%	0.518
Pre-index medication use
Insulin only (without other antihyperglycemics)	85	18.0%	92	19.5%	0.560
Non-insulin antihyperglycemics only	200	42.3%	175	37.0%	0.097
Insulin and other antihyperglycemics	118	24.9%	133	28.1%	0.269
Anxiolytics	81	17.1%	78	16.5%	0.794
Hypnotics	62	13.1%	71	15.0%	0.400
Antihypertensives	347	73.4%	362	76.5%	0.260
Statins	254	53.7%	238	50.3%	0.298
Systemic corticosteroids	45	9.5%	33	7.0%	0.156
Muscle relaxants	55	11.6%	50	10.6%	0.605
Total all-cause costs pre-index, $	16,635	36,560	17,024	45,797	0.885

Table 4.  Pre-index to post-index pDPN medication utilization.

	Pregabalin		Duloxetine		DID†	DID p-value
	Pre-index	Differences pre- to post-index*	Pre-index	Differences pre- to post-index*
Percentage with any pDPN-related analgesic	59.2%	40.8%	63.8%	36.2%	−4.7%	0.142
No. of unique pDPN-related analgesics	1.4 ± 1.8	1.2‡	1.5 ± 1.7	1.1‡	−0.1	0.302
Mean no. of pDPN-related prescriptions	2.9 ± 4.4	3.1‡	3.0 ± 3.9	2.9‡	−0.1	0.621
Non-opioid analgesics	22.4%	0.0%	22.4%	−3.2%	−3.2%	0.285
Opioid analgesics	14.6%	2.1%	13.5%	3.8%‡	1.7%	0.417
Strong only	8.0%	0.8%	7.8%	2.3%‡	1.5%	0.326
Weak only	6.1%	0.8%	5.3%	1.5%	0.6%	0.696
Both	0.4%	0.4%	0.4%	0.0%	−0.4%	0.480
Anticonvulsants
Pregabalin	0.0%	100.0%	0.0%	6.3%	−93.7%	<0.001
1st generation	1.1%	0.0%	1.1%	0.4%	0.4%	0.414
2nd generation other than pregabalin	23.0%	−9.5%‡	23.3%	0.2%	9.3%	0.001
Antidepressants
Duloxetine	0.0%	3.6%	0.0%	100.0%	96.4%	<0.001
Tricyclic antidepressants	10.8%	−2.1%	9.9%	−3.4%‡	−1.3%	0.471
Selective serotonin reuptake inhibitors	18.2%	1.5%	21.4%	−11.4%‡	−12.9%	<0.001
Serotonin norepinephrine reuptake  inhibitors other than duloxetine	4.7%	−0.2%	5.9%	−2.7%‡	−2.5%	0.028
Other antidepressants	8.5%	0.2%	8.5%	0.8%	0.6%	0.680
Lidocaine patch	2.1%	0.2%	3.0%	1.1%	0.8%	0.493
Anxiolytics	17.1%	0.4%	16.5%	1.5%	1.1%	0.612
Hypnotics	13.1%	2.5%	15.0%	0.8%	−1.7%	0.371

*Differences pre- to post-index are post-index minus pre-index.

†Difference-in-differences is duloxetine pre- to post-index differences minus pregabalin pre- to post-index differences.

‡Statistically significant difference pre- to post-index, at p < 0.050 significance level.

Table 5.  Unadjusted all-cause utilization differences pre-index to post-index and differences between cohorts.

All-cause utilization	Differences Pre- to post-index*		DID†	DID p-value
	Pregabalin	Duloxetine
Inpatient admissions
Patients with an admission	−3.6%	−7.0%‡	−3.4%	0.269
Admissions per patient (all patients)	−0.06	−0.11‡	−0.05	0.349
Length of stay	−2.4	−2.6	−0.3	0.891
Emergency department visits
Patients with a visit	−4.4%	0.8%	5.3%	0.117
Visits per patient (all patients)	−0.10	0.04	0.06	0.486
Physician office visits
Patients with a visit	−2.5%‡	−1.7%‡	0.8%	0.446
Visits per patient (all patients)	0.17	−0.52‡	−0.69	0.021
Other outpatient services
Patients with other services	−2.5%‡	−2.1%‡	0.4%	0.762
Other service visits per patient (all patients)	−0.46	−2.43‡	−1.98	0.256
Medication utilization
Prescriptions per patient	4.6‡	4.2‡	−0.4	0.626
Unique medications per patient	1.30‡	1.26‡	−0.04	0.916
Imputed absence hours	−5.0	−8.3‡	−3.3	0.545

*Differences pre- to post-index are post-index minus pre-index.

†Difference-in-differences (DID) is duloxetine pre- to post-index differences minus pregabalin pre- to post-index differences.

‡Statistically significant difference pre- to post-index, at p < 0.050 significance level.

Table 6.  Unadjusted all-cause and pDPN-attributable expenditures post-index, differences pre-index to post-index and differences between cohorts.

	Pregabalin		Duloxetine		DID†	DID p-value
	Post-index	Difference pre- to post-index*	Post-index	Difference pre- to post-index*
All-cause expenditures
Inpatient admissions	$4,743 ± 23,315	−$2,239	$4,063 ± 20,057	−$3,337	−$1,098	0.642
Emergency dept. visits	$215 ± 720	−$25	$282 ± 933	−$41	−$15	0.856
Physician office visits	$610 ± 501	−$2	$591 ± 483	−$90‡	−$88	0.004
Other outpatient services	$5,743 ± 22,343	−$116	$5,054 ± 16,644	−$518	−$402	0.572
Total medication	$3,164 ± 4,532	$645‡	$3,268 ± 2,647	$695‡	$51	0.616
Total all‐cause healthcare	$14,885 ± 38,320	−$1,750	$13,680 ± 31,208	−$3,344	−$1,594	0.550
Imputed all-cause absences	$663 ± 2,224	−$113	$514 ± 1,939	−$235	−122	0.465
pDPN-attributable Expenditures
pDPN-related analgesics	$824 ± 1,669	$476‡	$845 ± 804	$530‡	$53	0.221
Total pDPN	$1,996 ± 9,128	$267	$1,591 ± 3,982	−$1,186	−$1,454	0.088

*Expenditure differences are measured as the difference in the mean per member during the 6-month pre-index to 6-month post-index periods (post-index minus pre-index).

†Difference-in-differences (DID) is duloxetine pre- to post-index expenditure differences minus pregabalin pre- to post-index expenditure differences.

‡Statistically significant difference pre- to post-index, at p < 0.050 significance level.

Table 7.  Marginal effects comparing pregabalin and duloxetine for pDPN-specific medications, expenditures, and indirect costs.

Parameter	Marginal effect*	Standard error†	p-value	95% Confidence limits
Reference: duloxetine				Lower	Upper
Probability of opioid use	−0.013	0.013	0.328	−0.040	0.013
Number of pDPN-related analgesics used	0.108	0.162	0.506	−0.210	0.426
Total pDPN-attributable expenditure (2008 USD)	$145	$158	0.359	−$165	$454
Total all-cause expenditure (2008 USD)	$154	$1,174	0.895	−$2,147	$2,456
Probability of all-cause absence	0.034	0.028	0.215	−0.020	0.088
Indirect costs among individuals with any absence	−$458	$464	0.324	−$1,367	$452

*Marginal effects are the adjusted effects for the 6-month follow-up period.

†Standard errors of the marginal effects were computed using the delta method.