Real-world treatment pattern and outcomes among patients who took tapentadol IR or oxycodone IR

Abstract

Objective:

To evaluate differences in patient characteristics, healthcare resource utilization, and healthcare costs among patients receiving immediate release (IR) formulations of tapentadol (TAP IR) or oxycodone (OXY IR).

Methods:

Patients (≥18 years) who took TAP IR or OXY IR (6/1/2009–7/31/2011) were selected from the OptumInsight Clinformatics Data Mart claims database. Patients were assigned to the TAP IR or OXY IR cohort based on initial drug usage (index event). Continuous health plan coverage 60 days before (baseline period) and after (follow-up period) the index event was required. TAP IR patients were matched to OXY IR patients (1:1) using exact match of key patient characteristics and propensity score matching with patient demographics and clinical characteristics as covariates. T-test and chi-squared test were utilized to evaluate differences in patient characteristics, healthcare utilization and charges among cohorts.

Results:

Patient profiles during the baseline period significantly differed among TAP IR users (n = 17,539) and OXY IR users (n = 85,821) in the overall study population. The matched sample of TAP IR and OXY IR patients (n = 10,185 in both cohorts) had similar patient characteristics. During the 60-day follow-up period, patients who took TAP IR had a shorter mean hospital LOS (0.21 vs 0.35 days, p < 0.0001), a lower mean number of hospitalizations (0.07 vs 0.10, p < 0.0001), and lower mean inpatient ($2900 vs $4382, p < 0.001) and outpatient healthcare charges ($10,550 vs $11,084, p = 0.047). The higher index opioid prescription charge of TAP IR ($190 vs $150, p < 0.0001) was offset by other lower healthcare charges.

Conclusions:

The characteristics of patients who took TAP IR were different from patients who took OXY IR in many respects. In the sub-set of patients matched on demographic and clinical characteristics, those who took TAP IR used healthcare resources to a lesser extent, which was reflected in their lower healthcare charges, relative to OXY IR users.

Keywords::

• Opioid pain medications
• Tapentadol
• Oxycodone
• Healthcare resource utilization
• Healthcare charges

Introduction

Pain affects more Americans than diabetes, heart disease, and cancer combined1. It is estimated that 50 million Americans suffer from chronic pain resulting from a disease, disorder or accident, and that another 25 million have acute pain resulting from surgery or an accident2. The 2006 report from the National Center for Health Statistics states that 26% of Americans ≥20 years of age had a problem of pain persisting more than 24 hours, with adults ≥65 years of age experiencing pain much more frequently and for a longer duration than younger persons3. According to the National Institutes of Health, 80% of patients within nursing homes suffer pain, and their pain management is inadequate. Additionally, a survey conducted by the American Pain Society reported that 40% of people who suffer from moderate-to-severe pain do not find adequate pain relief2.

Unrelieved pain is associated with longer hospital stays, increased rates of re-hospitalization, and, consequently, higher healthcare costs4–6. Left unrelieved, prolonged acute pain can sensitize the central and peripheral nervous systems, leading to the development of chronic pain, a condition which is even more difficult to treat and associated with far greater healthcare costs1,3. The Institute of Medicine estimates that chronic pain costs the US at least $560–$635 billion (2010 dollars) annually1. This estimate includes the costs of healthcare, which ranges between $261 and $300 billion, and that due to lost productivity at work, and does not include the costs for acute pain1.

Opioid drugs are frequently used to manage moderate-to-severe pain. Tapentadol-immediate release (TAP IR) is a centrally-acting analgesic approved by both the FDA and DEA, and it became available in the US in June 2009 for the relief of moderate-to-severe acute pain in patients 18 years or older. While clinical outcomes of patients administered TAP IR have been assessed in clinical trials7–9, data is limited on the economic outcomes of patients administered TAP IR and those receiving other pain treatment in real-world clinical practice. This study was an early evaluation of patient characteristics, healthcare resource utilization, and related charges among patients who were initially treated with TAP IR or OXY IR.

Patients and methods

Study design

This was a retrospective database study involving two cohorts of patients, those who received TAP IR or OXY IR, a commonly prescribed scheduled II oral opioid medication, for pain management.

Study population

Patients (≥18 years of age) who received TAP IR or OXY IR between 6/1/2009 and 7/31/2011 were selected from the OptumInsight Clinformatics Data Mart managed care claims database. This claims database contains longitudinal patient-level details for 15 million patients and is a nationally representative integrated medical and pharmacy claims-based database. Patients were assigned to the TAP IR cohort based on their initial TAP IR usage (index event). Among patients not using TAP IR, patients were assigned to the OXY IR cohort based on their initial OXY IR usage (index event).

Continuous health plan coverage 60 days before (baseline period) and after (follow-up period) the index event were required for inclusion in the study population. Patients were grouped into an overall study population, with cohorts defined solely on index drug usage, with a sub-set grouped into matched cohorts (1:1) using a combination of exact match and propensity score matching with patient demographics and clinical characteristics as covariates. The matching covariates included age, gender, geographic region, presence of prior hospitalization, diagnosis-related group (DRG) of prior hospitalization, Charlson Comorbidity Index (CCI), which is used to measure overall disease severity and comorbidities, baseline presence of adverse event conditions, baseline resource utilizations, and baseline pain-related comorbidities. Since this study did not involve ‘identifiable human subjects’, it was exempted from Institutional Review Board overview under the Common Rule (45 CFR §46.101(b)(4))10.

Baseline measurements

Demographics consisting of age, age distribution, gender, state of residence, and health plan type and clinical and admission characteristics consisting of CCI score, prior hospitalizations, DRG description for prior hospitalization, comorbidities, and pain-related comorbidities were evaluated for patients within each of the cohorts in the overall and matched study populations during the baseline period.

Outcome measurements

The number of hospitalizations, total hospital length of stay (LOS), total healthcare charges, total inpatient charges, total outpatient medical service charges, total outpatient prescription drug charges, and index opioid prescription drug charges (mean ± standard deviation) were evaluated during the follow-up period among the matched cohorts. In this study charges from healthcare resource utilizations were used to represent the costs of corresponding healthcare services.

Statistical analyses

Logistic regression was used to generate the propensity score for matching of patients. T-test or chi-squared test was utilized where appropriate to determine differences in demographics, clinical and admission characteristics, hospitalization rates, LOS, and charges. A p-value of 0.05 was used to determine the level of statistical significance. All statistical analyses were carried out using SAS 9.2.

Results

Study populations

The total numbers of patients who received TAP IR or OXY IR in the unmatched cohorts were 17,539 and 85,821, respectively. Within the matched study population there were 10,185 patients in each cohort.

Patient demographics prior to matching

Among the unmatched cohorts demographics significantly differed (Table 1). The mean age of the TAP IR cohort was slightly lower (47.2 vs 47.6, p < 0.001), and a greater proportion were female (62% vs 52%, p < 0.001) in comparison to the OXY IR cohort. A significantly lower percentage of patients who took TAP IR had a Health Maintenance Organization (HMO) health plan (7% vs 14%, p < 0.001), with a greater proportion being covered by an Exclusive Provider Organization (16% vs 13%, p < 0.001) and Point-of-Service health plans (72% vs 66%, p < 0.001).

Table 1. Demographics of patients initially receiving TAP IR or OXY IR before and after matching.

	Unmatched				p-value	Matched
	TAP IR		OXY IR			TAP IR		OXY IR
	(n = 17,539)		(n = 85,821)			(n = 10,185)		(n = 10,185)
	n	%	n	%		n	%	n	%
Age
Mean (±SD)	47.2 ± 12.4		47.6 ± 14.0		<0.001	46.1 ± 11.7		46.1 ± 11.7
Median	48		49			47		47
Age groups					<0.001
<35 years	2988	17	17,288	20		1850	18	1867	18
35–44 years	4028	23	16,630	19		2431	24	2403	24
45–54 years	5319	30	22,921	27		3248	32	3238	32
55–64 years	4179	24	21,573	25		2335	23	2379	23
65–74 years	800	5	5104	6		288	3	261	3
≥75 years	225	1	2305	3		33	0.3	37	0.4
Gender					<0.001
Female	10,889	62	44,858	52		5888	58	5888	58
Male	6650	38	40,959	48		4297	42	4297	42
Unknown	0	0	4	0
State of residence* Unmatched/matched					<0.001
FL/FL	3692	21	10,560	12		2360	23	2417	24
GA/GA	2521	14	4577	5		1090	11	1194	12
MN/OH	83	0.5	7960	9		783	8	674	7
TX/NC	964	6	1975	2		492	5	490	5
WI/TX	168	1	5086	6		465	5	436	4
Health plan type					<0.001
EPO	2795	16	10,752	13		1597	16	1577	15
HMO	1285	7	12,039	14		806	8	826	8
Indemnity	257	1	2496	3		87	1	74	1
POS	12,630	72	56,608	66		7368	72	7404	73
PPO	572	3	3766	4		327	3	303	3
Other	0	0	160	0.2		0	0	1	0

SD, Standard deviation; EPO, Exclusive Provider Organization; HMO, Health Maintenance Organization; POS, Point of Service; PPO, Preferred Provider Organization.

*Only top five states of residence shown for cohorts.

Patient clinical and admission characteristics prior to matching

Of the overall study population, patients who received TAP IR had a significantly lower mean CCI score than those who received OXY IR (0.4 ± 1.1 vs 1.0 ± 2.1, p < 0.001) (Table 2). Patients who took TAP IR were also much less likely to have been recently hospitalized (8% vs 34%, p < 0.001) (Table 2). In both cohorts the majority of patients who were hospitalized were treated with pain medication after a major joint replacement or re-attachment of a lower extremity (TAP IR cohort: 22%; OXY IR cohort: 15%, p < 0.001).

Table 2. Baseline clinical and admission characteristics of patients initially receiving TAP IR or OXY IR before and after matching.

	Unmatched				p-value	Matched
	TAP IR		OXY IR			TAP IR		OXY IR
	(n = 17,539)		(n = 85,821)			(n = 10,185)		(n = 10,185)
	n	%	n	%		n	%	n	%
CCI
Mean (±SD)	0.4 (±1.1)		1.0 (±2.1)		<0.001	0.2 (±0.6)		0.2 (±0.6)
Median	0		0			0		0
CCI groups					<0.001
0	13,719	78	56,525	66		9072	89	9072	89
1–2	3134	18	19,000	22		1032	10	1032	10
3–4	435	2	4391	5		48	0.5	48	0.5
≥5	251	1	5905	7		33	0.3	33	0.3
Recently hospitalized					<0.001
Yes	1407	8	28,762	34		326	3	326	3
No	16,132	92	57,059	67		9859	97	9859	97
Baseline comorbidities
Hypertension	3069	20	20,946	25	<0.001	1452	14	1478	15
Diabetes	1248	8	8391	10	<0.001	396	4	396	4
Depression	1274	8	8142	10	<0.001	237	2	237	2
Anxiety	946	6	5480	7	0.020	142	1	142	1
Sleep disorders	1134	7	6114	7	0.804	529	5	522	5
Migraine	588	4	2397	3	<0.001	92	1	119	1
Asthma	563	4	3904	5	<0.001	153	2	157	2
Thyroid disorders	1085	7	5519	7	0.116	172	2	172	2
Seizure	115	0.7	1072	1.3	<0.001	36	0.4	49	1
Pain diagnoses
Back Pain	6712	38	25,190	29	<0.001	3133	31	3133	31
Neck Pain	3141	18	12,110	14	<0.001	1379	14	1398	14
Osteoarthritis	2209	13	12,277	14	<0.001	1094	11	1103	11
Fibromyalgia	1546	9	4324	5	<0.001	551	5	580	6
Rheumatoid Arthritis	289	2	1306	2	0.217	94	1	79	1
Diabetic Peripheral Neuropathy	142	0.8	851	1	0.024	1	0.01	1	0.01
Postherpetic Neuropathy	32	0.2	112	0.1	0.093	10	0.1	11	0.1
Other Neuropathic Pain	151	1	531	1	<0.001	56	0.6	46	0.5

CCI, Charlson Comorbidity Index; SD, Standard deviation.

Among the overall study population, patients who took TAP IR were less likely to have hypertension (20% vs 25%, p < 0.001), diabetes (8% vs 10%, p < 0.001), depression (8% vs 10%, p < 0.001), anxiety, (6% vs 7%, p = 0.020), asthma (4% vs 5%, p < 0.001), and seizures (0.7% vs 1.3%, p < 0.001), but more likely to be treated for migraines (4% vs 3%, p < 0.001) in comparison to patients who took OXY IR (Table 2).

Additionally, a greater proportion of patients who were prescribed TAP IR had back pain (38% vs 29%, p < 0.001), neck pain (18% vs 14%, p < 0.001), and fibromyalgia (9% vs 5%, p < 0.001) than patients prescribed OXY IR (Table 2). A slightly greater proportion of patients who took OXY IR had osteoarthritis (14% vs 13%, p < 0.001) and diabetic peripheral neuropathy (1.0% vs 0.8%, p = 0.024) in comparison to patients who took TAP IR (Table 2).

Demographics, clinical, healthcare resource utilization, and charges after patient matching

The matched cohorts were similar in all demographic and clinical characteristics at baseline (Table 2). Of note, the matching procedure ascertained that the proportion of patients with the various pain diagnoses (both nociceptive and neuropathic) were similar.

After matching for key patient characteristics, during the follow-up period, the TAP IR cohort had a lower mean number of hospitalizations (mean ± SD) (0.07 ± 0.29 vs 0.10 ± 0.37, p < 0.001) and shorter mean hospital LOS (0.21 ± 1.34 vs 0.35 ± 1.83 days, p < 0.001) (Figure 1). The lesser healthcare resource utilization for the TAP IR cohort was reflected in lower healthcare charges, such that the mean total healthcare charge ($14,423 ± $27,345 vs $16,502 ± $39,339, p < 0.001), inpatient charge ($2900 ± $17,017 vs $4382 ± $30,257, p < 0.001), outpatient charge ($10,550 ± $18,746 vs $11,084 ± $19,522, p = 0.047), and total prescription charge ($973 ± $1656 vs $1036 ± $1584, p = 0.006) were lower, relative to the OXY IR cohort (Figure 2). The mean charge for index prescription of TAP IR was slightly greater than that of OXY IR ($190 ± $209 vs $150 ± $290, p < 0.001).

Figure 1. Mean number of hospitalizations (a) and length of stay (b) associated with TAP IR and OXY IR treatment during the follow-up period after patient matching.

Figure 2. Mean total healthcare charges with breakdown (a) and opioid prescription charges (b) associated with TAP IR and OXY IR treatment during the follow-up period after patient matching.

In order to ensure that the analysis of differences of healthcare charges were not influenced by outliers in real-world clinical practice, we further carried out a sensitivity analysis by removing the top three charge outliers (both high and low) from the TAP IR and OXY IR cohorts, and then re-evaluated total healthcare charges. In this sensitivity analysis, the mean total healthcare charges were $13,265 for the TAP IR cohort and $15,097 for the OXY IR cohort (median: TAP IR: $3703, OXY IR: $3745; 25th percentile: TAP IR: $670, OXY IR: $581; 75th percentile: TAP IR: $15,001, OXY IR: $17,598). The results from this sensitivity analysis were consistent with the findings of the base case population.

Discussion

This study provides the first early evaluation of economic outcomes of patients prescribed TAP IR or OXY IR in real-world clinical practice. Of the overall study cohorts, patients prescribed TAP IR were slightly younger and a greater proportion were female than patients prescribed OXY IR. Also, TAP IR users were less sickly, as described by a lower mean CCI score and much less likely to have been recently hospitalized in comparison to OXY IR users; however, they had more pain-related comorbidity. The differences in patient characteristics between TAP IR and OXY IR users may influence the effectiveness of pain management drugs and analysis of economic outcomes.

In contrast to clinical trials, the patients within this large observational analysis were not randomized to achieve an equal distribution of patient demographics and clinical characteristics among treatment cohorts, and such differences on characteristics may produce biased estimates of treatment effects on outcomes. To minimize selection bias and confounding factors and their influences on outcomes, we used propensity score matching as a method of adjustment11. This technique controlled for many of the observable differences between patient cohorts by providing a summary measure of the conditional probability of being assigned to the TAP IR group based on a set of confounders (i.e., key demographics, prior hospitalizations, diagnosis-related group (DRG) of prior hospitalization, and comorbidities)11. Although the process of matching substantially reduced the original size of the study cohorts, the final matched cohorts included greater than 10,000 patients in each group and allowed for a more relevant evaluation of differences in healthcare resource utilization and charges among patients who used TAP IR or OXY IR.

Among hospitalized patients of the matched study cohorts, TAP IR usage was associated with a 40% shorter hospital stay, as well as 34% lower total inpatient charges, relative to usage of OXY IR. Additionally, total outpatient medical service charges were 10% lower for patients who took TAP IR. The slightly higher charge for TAP IR relative to OXY IR was outweighed by the reduction in other healthcare charges, which included inpatient and outpatient medical service charges and all prescription charges for patients who took TAP IR, relative to those who took OXY IR.

The results from the overall study cohorts showed that patients who initially received TAP IR more often had pain-related comorbidities, suggesting their pain management requires improvement in both the inpatient and outpatient care settings. Sub-optimal pain management over-burdens healthcare resources, affects patient quality-of-life, and comes at a substantial cost, healthcare and societal wise1. This is especially true when acute pain progresses to chronic pain. In future studies it will be important to compare clinical outcomes of patients using TAP IR and OXY IR in a variety of clinical settings wherein differences in patient characteristics, including pain frequency and severity, and specific causes of pain are taken into account, as these data will be important for clinical decision-makers.

Our study yields an early-view of informative results on patients who use TAP IR and OXY IR in the real world, but has some inherent limitations. Pain frequency and severity are not available in the database and, therefore, potential differences in these pain variables between treatment cohorts could not be accounted for, although types of pain conditions, comorbidities, and demographic characteristics were all taken into account. Despite these limitations, to our knowledge this is the first study that provides insights on the real world pattern of healthcare use and cost in a sub-set of matched TAP IR and OXY IR patients, and contributes to filling the information gap on health economic implications of short acting opioids. However, further investigation on the comparative effectiveness of these pain medications in a variety of different clinical settings is warranted. This study is subject to potential selection bias due to its non-randomized design; however, matching was conducted in order to minimize such bias. Coding errors, documentation errors, and incomplete information in the OptumInsight Clinformatics Data Mart claims database may affect data integrity, although these discrepancies would likely be equally distributed across both study cohorts.

Conclusions

When patient differences were taken into consideration, the results from this early evaluation suggest that TAP IR usage is associated with reduced hospitalizations, shorter hospital lengths of stay, and lower total healthcare charges, relative to OXY IR usage. Additional real-world studies are warranted to further validate these findings, as well as determine whether clinical outcomes differ among patients taking TAP IR and OXY IR.

Transparency

Declaration of funding

This research was supported by Janssen Scientific Affairs, LLC.

Declaration of financial/other interests

Jay Lin is an employee of Novosys Health, which has received research funds from Janssen Scientific Affairs, LLC in connection with conducting this study and development of this manuscript. Wing Chow, Myoung Kim, and Marcia Rupnow are employees of Janssen Scientific Affairs, LLC. JME Peer Reviewers on this manuscript have no relevant financial relationships to disclose.

Acknowledgements

The authors acknowledge Melissa Lingohr-Smith from Novosys Health in the editorial support and review of this manuscript.

Previous presentation

A related poster was presented at PAINWeek on September 6, 2012, in Las Vegas, Nevada.