Persistence and healthcare utilization associated with the use of buprenorphine/naloxone film and tablet formulation therapy in adults with opioid dependence

Figures & data

Figure 1. Cohort selection. BUP/NAL, buprenorphine/naloxone.

Figure 2. Population identification: patients in the database.

Figure 3. Kaplan Meier Curve: Time to discontinuation. BUP/NAL, buprenorphine/naloxone.

Table 1. ICD9-CM codes used for comorbidities.

Diagnosis	Code ICD-9-CM
Candiasis	‘112’ [Candiasis]
Chlamydia and gonococcus infections	‘098’ [Gonococcal infections] ‘099’ [Other venereal diseases]
Drugs abuse and dependence	‘V58.6’ [Long-term (current) drug use] ‘292’ [Drug psychoses] ‘305’ [Nondependent abuse of drugs] ‘303’ [Alcohol dependence syndrome] ‘304’ [Drug dependence] ‘96X’ and ‘97X’ [Poisoning by drugs, medicinal, and biological substances]
Drug and pregnancy	‘648.3’ [Drug dependence complicating pregnancy, childbirth, or the puerperium] ‘648.4’ [Mental disorders complicating pregnancy, childbirth, or the puerperium] ‘634’ [Spontaneous abortion] ‘764’ [Slow fetal growth and fetal malnutrition] ‘765’ [Disorders relating to short gestation and unspecified low birth weight]
Endocarditis	‘421.0’ [Acute and sub-acute bacterial endocarditis] ‘421.9’ [Acute endocarditis, unspecified]
HIV	‘042’ [Human immunodeficiency virus infection with specified conditions]
Hepatitis	‘070’ [Viral hepatitis]
Mental disorder (except drug use)	‘29X’, ‘30X’, and ‘31X’ [Mental disorders] and not ‘303’, ‘304’, ‘305’ [Psychoactive substance]
Acute pain	‘338.1’ [Acute pain]
Chronic pain	‘338.2’ [Chronic pain]
Phlebitis and thrombophlebitis	‘451’ [Phlebitis and thrombophlebitis]
Septicemia	‘038’ [Septicemia]
Soft tissues infections	‘683’ [Lymphadenitis, acute] ‘682’ [Other cellulitis and abscess] ‘680’ [Carbuncle and furuncle
Syphilis	‘09X’ [Syphilis and other venereal diseases]
Tetanus	‘037’ [Tetanus]
Tuberculosis	‘010’ [Primary tuberculous infection] ‘011’ [Pulmonary tuberculosis] ‘012’ [Other respiratory tuberculosis] ‘013’ [Tuberculosis of meninges and central nervous system] ‘014’ [Tuberculosis of intestines, peritoneum, and mesenteric glands] ‘015’ [Tuberculosis of bones and joints] ‘016’ [Tuberculosis of genitourinary system] ‘017’ [Tuberculosis of other organs] ‘018’ [Miliary tuberculosis]

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

Table 2. Patient characteristics at index date, by formulation.

Characteristic	BUP/NAL		p-value
	Tablet	Film
Gender
Female	563 (37.28%)	961 (34.38%)	0.06
Male	947 (62.72%)	1834 (65.62%)
Age
Mean (SD)	35.65 (12.32)	34.34 (11.83)	0.001
95% CI	35.03; 36.27	33.90; 34.77
Region
West	211 (14.00%)	416 (14.89%)	0.01
Midwest	310 (20.57%)	558 (19.97%)
South	757 (50.23%)	1489 (53.29%)
Northeast	229 (15.20%)	331 (11.85%)
Insurance plan product
EPO	234 (15.50%)	397 (14.20%)	0.12
HMO	110 (7.28%)	230 (8.23%)
Indemnity	1 (0.07%)	8 (0.29%)
Point of service	1110 (73.51%)	2084 (74.54%)
PPO	54 (3.58%)	77 (2.75%)
Follow-up duration
Mean (SD)	412.81 (236.22)	292.70 (185.93)	<0.0001
95% CI	400.88; 424.73	285.81; 299.60
Min–Max	24.00–851.00	30.00; 826.00
Daily dose at index date (mg)
0–8	500 (33.11%)	779 (27.86%)	<0.0001
8–12	114 (7.55%)	194 (6.94%)
12–16	560 (37.09%)	1175 (42.02%)
16+	336 (22.25%)	648 (23.18%)
Comorbidities 12 months before index date
Drugs abuse	1134 (75.10%)	2159 (77.22%)	0.12
Hepatitis	46 (3.05%)	75 (2.68%)	0.49
Mental disorder (except drug use)	1010 (66.89%)	1728 (61.80%)	0.001
Acute pain	98 (6.49%)	151 (5.40%)	0.14
Chronic pain	208 (13.77%)	332 (11.87%)	0.07
Soft tissues infections	128 (8.48%)	219 (7.83%)	0.46
≥1 diagnosis of opioid dependence or abuse in the 12 months before index date	800 (52.98%)	1587 (56.76%)	0.02
≥1 opioid prescription	1044 (69.14%)	1856 (66.38%)	0.07
≥1 chronic pain diagnosis	208 (13.77%)	332 (11.87%)	0.07
≥1 opioid prescription or one chronic pain diagnosis	1056 (69.93%)	1866 (66.74%)	0.03
≥1 acute pain diagnosis	98 (6.49%)	151 (5.40%)	0.14
% copayment of the index date prescription
Mean (SD)	15.61 (13.50)	15.19 (12.15)	0.59
95% CI	14.93; 16.29	14.74; 15.64

BUP/NAL, buprenorphine/naloxone; EPO, Exclusive Provider Organization; HMO, Health Maintenance Organization; PPO, Preferred Provider Organization; SD, Standard Deviation; CI, Confidence Interval.

Table 3. Adjusted healthcare costs and resource utilization in the 12 months before and after index date.

	12 months before index date			12 months after index date
Resource utilization	BUP/NAL tablet (n = 1503)	BUP/NAL film (n = 2779)	p-value	BUP/NAL tablet (n = 775)	BUP/NAL film (n = 857)	p-value
Pharmacy claims
Mean	28.32	26.76	0.0893	33.61	32.71	0.2624
CI	[24.37;32.90]	[23.16;30.92]		[27.65;40.85]	[26.95;39.70]
Probability to have at least one hospitalization
Mean	0.34	0.3	0.004	0.23	0.19	0.0158
CI	[0.30;0.39]	[0.26;0.35]		[0.20;0.25]	[0.17;0.22]
Probability to have at least one ER visit
Mean	0.14	0.12	0.1306	0.11	0.1	0.3852
CI	[0.12;0.15]	[0.11;0.13]		[0.09;0.13]	[0.08;0.12]
Outpatient visits
Mean	8.74	8.93	0.2074	9.51	9.88	0.0185
CI	[7.96;9.61]	[8.14;9.80]		[8.60;10.52]	[8.95;10.92]
Costs
Pharmacy
Mean	2,546	2,008	<0.0001	4,467	4,028	0.0039
CI	[1,988;3,260]	[1,582;2,549]		[2,886;6,963]	[2,586;6,275]
Hospitalization
Mean	9,987	7,534	0.0049^+	8,198	5,371	0.0806^+
CI	[7,105;14,038]	[4,562;10,392]	0.0040^++	[5,550;12,111]	[3,499;8,245]	0.0158^++
ER visit
Mean	91	66	0.0842^+	79	57	0.3917^+
CI	[63;130]	[48;91]	0.1306^++	[42;145]	[28;112]	0.3852^++
Outpatient
Mean	7,066*	6,478*	0.0485	6,668*	5,507*	0.0104
CI	[5,799;8,612]	[5,346;7,849]		[2,685;16,558]	[2,217;13,676]
Total healthcare costs
Mean	20,632	17,772	0.0008	19,853	14,431	<0.0001
CI	[16,895;25,195]	[14,644;21,569]		[4,515;87,291]	[3,277;63,532]

BUP/NAL, buprenorphine/naloxone; CI, Confidence interval.

*Costs associated with all the outpatient claims (not only visits).

+from generalized linear model on; ++ from logistic model.

Table 4. Generalized linear models* on total healthcare costs in the 6 and 12 months post-index periods.

Parameter	Category	6 months after index date (tablet: 1165 patients; Film: 1751 patients)				12 months after index date (tablet: 775 patients; Film: 857 patients)
		Cost ratio	Confidence interval		p-value	Cost ratio	Confidence interval		p-value
Intercept**		8912	6103	13,016	<0.0001	16,897	10,573	27,000	<0.0001
ITT at index date [REF: BUP/NAL tablet]	BUP/NAL film	0.76	0.68	0.84	<0.0001	0.73	0.63	0.84	<0.0001
Diagnosis of Mental disorder 12 m prior index date		1.08	0.93	1.25	0.308	1.21	1.00	1.47	0.0524
Gender [REF: Male]	Female	1.02	0.91	1.14	0.7709	1.01	0.88	1.15	0.9295
Health insurance plan [REF: PPO/Other]	EPO	0.83	0.62	1.11	0.2071	0.74	0.50	1.09	0.1307
	HMO	0.83	0.60	1.16	0.2755	0.80	0.52	1.24	0.3254
	IND	1.72	0.85	3.51	0.1324	0.58	0.00	927.32	0.8845
	POS	0.95	0.73	1.22	0.6721	1.01	0.73	1.40	0.9633
Age [REF: 18 years]		0.99	0.99	1.00	0.0001	0.99	0.98	0.99	0.0002
Total costs 12 months prior to index date	2nd quartile	1.59	1.17	2.17	0.0028	1.23	0.84	1.81	0.2808
[REF: 1st quartile]	3rd quartile	2.19	1.63	2.93	<0.0001	1.99	1.40	2.81	0.0001
	4th quartile	3.60	2.72	4.76	<0.0001	3.31	2.38	4.61	<0.0001
Daily dose at index date		0.99	0.98	1.00	0.0453	0.99	0.99	1.00	0.2176

BUP/NAL, buprenorphine/naloxone; PPO, Preferred Provider Organization; EPO, Exclusive Provider Organization; HMO, Health Maintenance Organization; IND, Indemnity plan; POS, Point of Service; IIT, Intent to treat.

*Generalized linear model with log link function and Gaussian distribution.

**Represents mean cost for reference patient (tablet, with diagnosis of mental disorder before index date, male, with PPO/other insurance plan, aged 18 years, total charge before index date in 1st quartile).

Table 5. Generalized linear model* on total monthly costs, by treatment phase.

Parameter	Category	Cost ratio	Confidence interval		p-value
Intercept		979.46**	743.52	1290.26	<0.0001
Treatment phase [REF: Tablet - Before treatment]	Tablet - Initiation	2.47	2.16	2.82	<0.0001
	Tablet - Treatment	1.06	0.92	1.22	0.4212
	Tablet - Discontinuation	1.51	1.18	1.93	0.001
	Tablet - After treatment	1.16	0.92	1.48	0.2131
	Tablet - Re-initiation	1.28	1.00	1.64	0.0515
	Film - Before treatment	0.80	0.69	0.93	0.0034
	Film - Initiation	1.69	1.46	1.97	<0.0001
	Film - Treatment	0.84	0.72	0.97	0.02
	Film - Discontinuation	1.30	1.02	1.67	0.0338
	Film - After treatment	0.95	0.77	1.17	0.6189
	Film - Re-initiation	1.24	0.86	1.79	0.2519
Gender [REF: Male]	Female	1.10	0.99	1.23	0.0866
Age [REF: 18years]		1.00	0.99	1.00	0.7803
Geographical area [REF: Northeast]	West	0.94	0.77	1.16	0.5806
	Midwest	1.23	1.02	1.48	0.0293
	South	1.00	0.83	1.19	0.9799
Health insurance plan [REF: PPO + IND + HMO]	EPO	1.03	0.86	1.24	0.7501
	POS	1.06	0.91	1.24	0.4253
Diagnosis of Mental disorder 12 m prior index date		2.00	1.75	2.28	<0.0001

BUP/NAL, buprenorphine/naloxone; PPO, Preferred Provider Organization; EPO, Exclusive Provider Organization; HMO, Health Maintenance Organization; IND, Indemnity plan; POS, Point Of Service.

*Repeated measures generalized linear model with log link function and Gaussian distribution.

**Represents mean cost ($) for reference patient-month (tablet group, before treatment, male, aged 18 years, living in Northeast region, with PPO/other insurance plan, diagnosis of mental disorder before index date).