Burden of opioid use for pain management among adult herpes zoster patients in the US and the potential impact of vaccination

Figures & data

Table 1. List of HZ-/PHN-related medications and pain medications

Class	Generic names
HZ-/PHN-related medications
Antivirals (oral and intravenous)	Acyclovir, valacyclovir, famciclovir
Non-opioid pain-related medications
Analgesic agents	Acetaminophen, nonsteroidal anti-inflammatory drugs
Anticonvulsants	Gabapentin, pregabalin
Benzodiazepines	Adinazolam, alprazolam, chlordiazepoxide, climazolam, clobazam, clonazepam, clorazepate, diazepam, estazolam, flurazepam, halazepam, loprazolam, lorazepam, lormetazepam, midazolam, nimetazepam, nitrazepam, oxazepam, prazepam, temazepam, triazolam, quazepam
Oral corticosteroids	Prednisone, hydrocortisone, prednisolone, methylprednisolone, triamcinolone, paramethasone, dexamethasone, betamethasone
Tricyclic antidepressants	Amitriptyline, desipramine, nortriptyline
Topical pain relievers	Capsaicin, lidocaine
Muscle relaxants	Flexeril (cyclobenzaprine)
Other medications	Memantine
Opioids
Weak opioids	Codeine, dihydrocodeine, hydrocodone, pentazocine, propoxyphene, tramadol
Strong opioids	Buprenorphine, diamorphine, fentanyl, hydromorphone, meperidine, methadone, morphine, oxymorphone, oxycodone

HZ: herpes zoster; PHN: postherpetic neuralgia.

Source: Fashner and Bell (2011).²⁰

Figure 1. Flow chart of selection of subjects from (a) commercial/Medicare databases and (b) Medicaid database.

HZ: herpes zoster; PHN: postherpetic neuralgia.

Table 2. Demographic and clinical characteristics - matched populations

Characteristic, Statistics	Opioid HZ cohort, N = 39,299	Non-HZ cohort, N = 196,495
Age, mean (SD)	51.0 (15.8)	50.2 (16.7)
Male, %	41.1%	41.1%
Commercial or Medicare payer, %	91.5%	91.5%
Health plan type, %
Health maintenance organization	14.8%	13.1%
Preferred provider organization	51.3%	50.4%
Point of service	6.3%	6.2%
Other	26.6%	25.4%
Missing/unknown	1.0%	4.9%
Geographic region, %
Northeast	14.0%	16.8%
North central	21.0%	20.5%
South	40.9%	38.1%
West	15.3%	13.8%
Unavailable (Medicaid subjects)	8.5%	10.5%
CCI score, mean (SD)^a	0.8 (1.4)	0.8 (1.4)
Common CCI comorbidities, %
Hypertension	25.2%	23.7%
Diabetes	10.2%	10.0%
Chronic pulmonary disease	6.2%	6.6%
Patients with an immunocompromised diagnosis,	12.4%	12.4%
Common immunocompromised diagnoses^c
Cancer	5.9%	4.9%
Solid organ transplant	3.9%	4.5%
Patients with an HZ-related complication	44.7%	NA
Types of HZ-related complications observed
PHN	42.7%	NA
Cutaneous complications	2.2%	NA
Neurological complications (excluding PHN)	0.4%	NA
Ophthalmic complications	4.8%	NA

CCI: Charlson Comorbidity Index; HZ: herpes zoster; PHN: postherpetic neuralgia; SD: standard deviation.

^aThe CCI was calculated based on data recorded during the 6 months prior to the HZ index date.²¹

Table 3. Opioid dosage patterns

Opioid HZ cohort
Characteristic, statistic	41,065	100.0%
Days opioid medication supplied
Mean (SD)	5.9	5.3
Median	5
Minimum, maximum	1.0	90
Opioid dose at initiation (morphine milligram equivalent in mg)
Mean (SD)	6.2	2.1
Median	5
Minimum, maximum	1.8	60
Number of opioid prescriptions during the postindex period
Mean (SD)	1.6	1.6
Median	1
Minimum, maximum	1	35
Number of opioid prescriptions filled during the postindex period
1	28,070	68.4%
2	7,676	18.7%
3	2,622	6.4%
4 +	2,697	6.6%
Days from HZ index date to first observed opioid prescription
Mean (SD)	75.3	109.0
Median	3.0
Minimum, maximum	1.0	366.0
Patients filling a prescription for an opioid during each month of the follow-up period (N, %)
Month 1	25,203	61.4%
Month 2	3,194	7.8%
Month 3	2,915	7.1%
Month 4	2,935	7.1%
Month 5	2,836	6.9%
Month 6	2,921	7.1%
Month 7	2,816	6.9%
Month 8	2,815	6.9%
Month 9	2,953	7.2%
Month 10	2,872	7.0%
Month 11	2,883	7.0%
Month 12	3,058	7.4%
Opioid dose escalation during the postindex period
No	36,609	89.1%
Yes	4,456	10.9%
Patients switched from weak to strong opioids during the postindex period
No	38,596	94.0%
Yes	2,469	6.0%

HZ: herpes zoster; SD: standard deviation.

Table 4. Factors associated with receipt of opioid medication from multivariable logistic regression analysis – commercial database

Factor	Odds Ratio (95% CI)	P
Presence of HZ complications (versus no complications)
PHN (versus no PHN)	2.35 (2.28; 2.42)	<0.01
Cutaneous complications	0.95 (0.87; 1.05)	0.34
Neurological complications (excluding PHN)	1.05 (0.84; 1.30)	0.68
Ophthalmic complications	0.82 (0.77; 0.88)	<0.01
Age on HZ index date (versus <50 years)
50–54 years	1.05 (1.01; 1.09)	0.02
55–59 years	1.06 (1.03; 1.10)	<0.01
60–64 years	1.04 (1.00; 1.09)	0.04
Males (versus females)	1.01 (0.98; 1.04)	0.55
Health plan type (versus health maintenance organization
Preferred provider organization	1.06 (1.01; 1.10)	0.01
Point of service	1.13 (1.06; 1.21)	<0.01
Other	1.06 (1.01; 1.12)	0.02
Geographic region (versus Northeast)
North Central	1.46 (1.40; 1.53)	<0.01
South	1.71 (1.64; 1.78)	<0.01
West	1.57 (1.50; 1.65)	<0.01
Year of HZ index date (versus 2014)
2015	0.93 (0.90; 0.96)	<0.01
2016	0.83 (0.80; 0.86)	<0.01
2017	0.74 (0.70; 0.79)	<0.01
CCI score (versus CCI score = 0)
CCI score 1	1.14 (1.10; 1.18)	<0.01
CCI score 2	1.26 (1.19; 1.33)	<0.01
CCI score 3	1.24 (1.14; 1.35)	<0.01
CCI score ≥4	1.38 (1.28; 1.50)	<0.01
Presence of immunocompromised status (versus no immunocompromised diagnosis)	1.21 (1.15; 1.27)	<0.01

CCI: Charlson Comorbidity Index; CI: confidence interval; HZ: herpes zoster; P, P-value; PHN: postherpetic neuralgia.

Figure 2. Adjusted health care costs by time from HZ Index date and by type of complication.

HZ: herpes zoster; PHN: postherpetic neuralgia.

Table 5. Adjusted health care costs by time from HZ index date and by payer

Opioid HZ cohort vs non-opioid HZ cohorts
	Overall			Commercial			Medicare			Medicaid
Time period after the index date	Opioid HZ cohort	Non-opioid HZ cohort	Difference	Opioid HZ cohort	Non-opioid HZ cohort	Difference	Opioid HZ cohort	Non-opioid HZ cohort	Difference	Opioid HZ cohort	Non-opioid HZ cohort	Difference
Month 1	$2,545	$1,317	$1,228	$2,663	$1,375	$1,288	$3,285	$1,822	$1,463	$1,383	$1,107	$276
Month 2	$2,208	$1,104	$1,104	$2,443	$1,204	$1,239	$2,478	$1,473	$1,005	$1,392	$1,227	$165
Month 3	$2,235	$1,078	$1,157	$2,464	$1,183	$1,281	$2,692	$1,477	$1,215	$1,894	$1,467	$427
Quarter 1	$6,081	$2,845	$3,236	$6,759	$3,136	$3,623	$7,815	$4,294	$3,521	$4,145	$3,214	$931
Quarter 2	$5,899	$2,667	$3,232	$6,134	$2,748	$3,386	$6,823	$3,713	$3,110	$4,439	$3,192	$1,247
Year 1	$23,599	$9,937	$13,662	$25,389	$10,650	$14,739	$27,862	$15,699	$12,163	$20,048	$13,730	$6,318
Opioid HZ cohort vs matched non-HZ cohort
	Overall			Commercial			Medicare			Medicaid
Time period after the index date	Opioid HZ cohort—matched	Matched non-HZ cohort	Difference	Opioid HZ cohort—matched	Matched non-HZ cohort	Difference	Opioid HZ cohort—matched	Matched non-HZ cohort	Difference	Opioid HZ cohort—matched	Matched non-HZ cohort	Difference
Month 1	$2,329	$1,118	$1,211	$2,298	$1,287	$1,011	$3,048	$1,645	$1,403	$1,378	$1,023	$355
Month 2	$2,178	$1,028	$1,150	$2,381	$1,029	$1,352	$2,356	$1,389	$967	$1,287	$1,185	$102
Month 3	$2,089	$987	$1,102	$2,310	$1,018	$1,292	$2,519	$1,369	$1,150	$1,890	$1,329	$561
Quarter 1	$5,812	$2,516	$3,296	$6,429	$2,891	$3,538	$7,618	$4,109	$3,509	$4,099	$3,105	$994
Quarter 2	$5,690	$2,128	$3,562	$5,981	$2,579	$3,402	$6,694	$3,683	$3,011	$4,328	$3,078	$1,250
Year 1	$21,892	$9,104	$12,788	$24,971	$9,872	$15,099	$26,955	$15,088	$11,867	$19,873	$13,029	$6,844

HZ: herpes zoster.

Table 6. Health care resource utilization and costs, by cohort (month 1 after the index date)

	Unmatched patients				Matched patients
Characteristic	Opioid HZ cohort (N = 41,065)		Non-opioid HZ cohort (N = 83,941)		Opioid HZ cohort—matched (N = 39,299)		Non-HZ cohort—matched (N = 196,495)
Inpatient services
≥1 hospital admission (N, %)	992	2.4%	679	0.8%	875	2.2%	1,589	0.8%
Number of admissions
Mean (SD)	0.0	0.2	0.0	0.1	0.0	0.2	0.0	0.1
Median	0.0		0.0		0.0		0.0
Range (minimum, maximum)	0.0	4.0	0.0	5.0	0.0	4.0	0.0	5.0
Total hospital days
Mean (SD)	4.7	5.3	4.5	5.7	4.5	4.9	4.4	6.0
Median	3.0		3.0		3.0		3.0
Range (minimum, maximum)	1.0	64.0	1.0	92.0	1.0	64.0	1.0	96.0
Inpatient costs
Mean (SD)	$603	$7,053	$176	$3,619	$539	$6,646	$187	$5,180
Median	$0		$0		$0		$0
Range (minimum, maximum)	$0	$561,232	$0	$436,417	$0	$561,232	$0	$1,425,620
ED visits
≥1 ED visit (N, %)	9,065	22.1%	7,941	9.5%	8,601	21.9%	4,729	2.4%
Number of unique days with an ED visit
Mean (SD)	0.3	0.6	0.1	0.3	0.3	0.6	0.0	0.2
Median	0.0		0.0		0.0		0.0
Range (minimum, maximum)	0.0	14.0	0.0	6.0	0.0	14.0	0.0	12.0
ED costs
Mean (SD)	$176	$788	$64	$504	$173	$770	$25	$354
Median	$0		$0		$0		$0
Range (minimum, maximum)	$0	$37,261	$0	$33,902	$0	$37,261	$0	$44,183
Outpatient hospital visits
≥1 outpatient hospital visits (N, %)	10,506	25.6%	12,852	15.3%	9,848	25.1%	21,025	10.7%
Number of unique days with an outpatient hospital visit
Mean (SD)	0.4	0.9	0.2	0.7	0.4	0.9	0.2	0.7
Median	0.0		0.0		0.0		0.0
Range (minimum, maximum)	0.0	26.0	0.0	23.0	0.0	26.0	0.0	31.0
Outpatient hospital costs
Mean (SD)	$351	$2,372	$141	$1,396	$336	$2,305	$190	$2,109
Median	$0		$0		$0		$0
Range (minimum, maximum)	$0	$169,758	$0	$156,599	$0	$169,758	$0	$235,502
Physician office visits
≥1 physician office visit (N, %)	35,199	85.7%	74,864	89.2%	33,681	85.7%	69,192	35.2%
Number of unique days with a physician office visits
Mean (SD)	1.8	1.6	1.7	1.4	1.8	1.6	0.7	1.3
Median	1.0		1.0		1.0		0.0
Range (minimum, maximum)	0.0	31.0	0.0	31.0	0.0	31.0	0.0	31.0
Physician office visit costs
Mean (SD)	$274	$863	$236	$523	$271	$860	$123	$666
Median	$147		$135		$145		$0
Range (minimum, maximum)	$0	$69,031	$0	$35,994	$0	$69,031	$0	$134,610
Pharmacy
≥1 prescription (N, %)	39,861	97.1%	82,374	98.1%	38,147	97.1%	95,425	48.6%
Number of prescription claims
Mean (SD)	4.1	2.9	2.8	2.1	4.0	2.9	1.5	2.4
Median	3.0		2.0		3.0		0.0
Range (minimum, maximum)	0.0	131.0	0.0	54.0	0.0	131.0	0.0	50.0
Pharmacy costs
Mean (SD)	$285	$1,029	$233	$1,088	$275	$998	$164	$953
Median	$61		$45		$60		$0
Range (minimum, maximum)	$0	$37,980	$0	$102,224	$0	$37,980	$0	$95,778
Other medical encounters
≥1 other medical encounter (N, %)	11,430	27.8%	20,561	24.5%	10,817	27.5%	24,040	12.2%
Number of unique days with other medical encounters
Mean (SD)	0.5	1.4	0.4	1.3	0.4	1.4	0.2	1.2
Median	0.0		0.0		0.0		0.0
Range (minimum, maximum)	0.0	31.0	0.0	31.0	0.0	31.0	0.0	31.0
Other medical encounter costs
Mean (SD)	$146	$1,557	$88	$1,078	$137	$1,532	$85	$1,140
Median	$0		$0		$0		$0
Range (minimum, maximum)	$0	$136,228	$0	$140,764	$0	$136,228	$0	$144,350
Total health care costs
Mean (SD)	$1,834	$8,243	$939	$4,565	$1,731	$7,845	$775	$6,037
Median	$419		$294		$409		$39
Range (minimum, maximum)	$0	$565,076	$0	$438,574	$0	$565,076	$0	$1,441,256

ED: emergency department; HZ: herpes zoster; SD: standard deviation.

Figure 3. Adjusted health care costs in the 1-year after the HZ index date, by age.

Left: non-matched cohorts HZ-population; Right: matched cohorts, matched opioid cohort and matched non-HZ cohort.

HZ: herpes zoster; Y: years.

Figure 4. HZ-related prescriptions avoided with RZV vaccination in a population of 1 million adults aged ≥50 years .

^aCalculated based on the size of the population vaccinated with RZV and the NNV to avoid one HZ case from RZV cost-effectiveness model.⁴¹

^bCalculated based on number of HZ cases prevented and painkiller prescription rates.

HZ: herpes zoster; NNV: number needed to vaccinate; RZV: recombinant zoster vaccine

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