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Differences Between COPD Patients Prescribed Revefenacin and Tiotropium Bromide Post-Hospitalization

Differences Between COPD Patients Prescribed Revefenacin and Tiotropium Bromide Post-Hospitalization

 

This real-world evidence study examined demographic and clinical characteristic differences between COPD patients prescribed revefenacin (a nebulized long-acting muscarinic antagonist [LAMA]) or tiotropium bromide (a handheld administered LAMA) following a COPD hospitalization using two observational claims databases. The study period extended from November 9, 2017 through October 31, 2021 and included patients with a COPD-related inpatient hospitalization who received their LAMA within 90 days post-discharge. Compared with patients who received tiotropium bromide (n =5,549), patients receiving revefenacin (n = 456) were older (mean ± standard deviation [SD]): 74.8 ± 7.82 vs. 70.4 ± 10.3; p < 0.001) and had a higher proportional representation in the Medicare Fee-for-Service (FFS) payer group (92.5% vs. 70.6%; p < 0.001). Additionally, the revefenacin cohort was more likely to present a mean Deyo-Charlson Comorbidity Index (CCI) score ≥ 3 (58.1% vs. 54.3%) and were also more likely to be treated with nearly all available maintenance medications prior to the index COPD-hospitalization compared to the tiotropium bromide cohort, including inhaled corticosteroids (34.9% vs. 8.4%), long-acting β2-agonists (32.7% vs. 3.1%), and leukotriene modifiers (16.0% vs. 8.4%; two-sided p’s < 0.01). Given these results, it is concluded the Revefenacin patients were sicker, and therefore suggest that patients taking revefenacin and tiotropium bromide are separate segments of patients with COPD. 

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Background

Chronic obstructive pulmonary disease (COPD) is a progressive pulmonary disease characterized by persistent airflow limitation.1,2 Patients with COPD often have periods of acute worsening of symptoms, known as disease exacerbations,3 which if severe, can result in hospitalization. As such, the reduction of exacerbation severity and frequency is a primary clinical aim. Mechanism of medication delivery is extremely critical, however nearly 20% of patients with advanced COPD do not achieve the necessary peak inspiratory flow to inhale medications delivered via dry powder inhaler.4 Additionally, issues of dexterity and cognitive impairment have also been  shown to affect medication delivery across devices.5-7 As such, patients presenting with any of these issues are often recommended treatment with a nebulizer,8,9 which is generally associated with fewer administration-related challenges.10 To address limitations of the extant literature, we examined the demographic and clinical characteristics of patients with COPD in the Medicare FFS and MORE2 Registry® databases who were prescribed revefenacin delivered via nebulization or tiotropium bromide (“tiotropium” hereafter) delivered via hand-held inhaler post-COPD hospitalization discharge. 

Results

A total of 6,005 patients aged 40+ were included in the study, with 456 (7.6%) receiving revefenacin and 5,549 (92.5%) receiving tiotropium.  Compared with patients who received tiotropium, patients receiving revefenacin were older (mean ± standard deviation [SD]): 74.8 ± 7.82 vs. 70.4 ± 10.3; p < 0.001), had a higher proportion of White individuals (88.2% vs. 76.2%,  had a higher proportional representation in the Medicare FFS payer group (92.5% vs. 70.6%, p < 0.001), and were more likely to reside in the Southern region of the US (39.7% vs. 26.4%, p < 0.001). Additionally, among Medicare beneficiaries, revefenacin patients had a higher proportion qualifying for old age and survivors insurance as the original reason for entitlement (85.7% vs. 58.7%, p < 0.001), and had a higher proportion who did not qualify for Low Income Subsidy Status for Medicare Prescription Drug Coverage (77.0% vs. 69.8%, p < 0.01) compared with the tiotropium group (Table 1).

Table 1. Demographic characteristics of COPD patients treated with revefenacin or tiotropium post-hospitalization

 

Revefenacin Cohort

Tiotropium 

Cohort

Two-Sided p-Value

N =

456

N =

5,549

Mean/N

SD/%

Mean/N

SD/%

Age (M, SD)

74.75

7.82

70.38

10.30

Race/Ethnicity (N, %)

<.0001

White

402

88.2%

4226

76.2%

Black or African American

21

4.6%

507

9.1%

Other 

33

7.2%

816

14.7%

Census Region (N, %)

<.0001

Northeast

58

12.7%

769

13.9%

Midwest

140

30.7%

967

17.4%

South

181

39.7%

1465

26.4%

West

43

9.4%

713

12.8%

Unknown

34

7.5%

1635

29.5%

Dual Eligible Status1 (N, %)

0.0067

No

364

79.8%

4110

74.1%

Yes

92

20.2%

1439

25.9%

Low Income Subsidy (LIS) Status for Medicare Prescription Drug Coverage2 (N, %)

     0.0013

No

351

77.0%

3874

69.8%

Yes

            105

23.0%

1675

30.2%

Compared with the tiotropium cohort, patients in the revefenacin cohort had a slightly higher mean Deyo-Charlson Comorbidity Index (DCI) score (4.8 ± 3.2 vs. 4.6 ± 3.2; p < 0.001) and were more likely to present a mean DCI score ≥ 3 (58.1% vs. 54.3%). However, revefenacin patients presented lower proportions of a number of individual comorbid conditions, including anxiety (2.4% vs. 12.8%), cardiovascular disease (3.1% vs. 11.5%), COVID-19 (6.8% vs. 25.1%), and hypertension (6.6% vs. 23.2%; p’s < 0.001) 

Interestingly, the revefenacin cohort presented a lower proportion of patients with a cognitive or motor disorder (3.3% vs. 13.3%, p < 0.001). Additionally, revefenacin patients were more likely be to be treated with nearly all available maintenance medications, including inhaled corticosteroids (34.9% vs. 8.4%), long-acting β2-agonists (LABA; 32.7% vs. 3.1%), LAMA (12.9% vs. 4.9%), leukotriene modifiers (16.0% vs. 8.4%), macrolide antibiotics (45.4% vs. 36.1%), methylxanthines (4.4% vs. 0.8%), PDE-4 inhibitors (5.7% vs. 2.2%), short-acting β2-agonists (SABA; 75.0% vs. 65.8%), short-acting muscarinic antagonists (SAMA; 13.8% vs. 6.8%), and systemic corticosteroids (80.7% vs. 64.3%, ps < 0.01).  Further, revefenacin patients were more likely to also utilize baseline oxygen therapy (57.5% vs. 29.0%, p < 0.001) compared with tiotropium patients. Conversely, the tiotropium group had a higher proportion of ICS/LABA use (35.3% vs. 27.6%, p < 0.001). Finally, patients in the revefenacin group incurred higher annual mean and median baseline healthcare costs compared with the tiotropium group (mean ± SD (median)): $45,577 ± $44,473 ($31,930) vs. $42,580 ± $45,180 ($26,558) (p < 0.001; Table 2). 

Table 2. 12-Month baseline clinical characteristics of COPD patients treated with revefenacin or tiotropium post-hospitalization

 

Revefenacin Cohort

Tiotropium 

Cohort

Two-Sided p-Value

N =

456

N =

5,549

Mean/N

SD/%

Mean/N

SD/%

Deyo-Charlson Comorbidity Index (DCI) score (Mean, SD)

4.8

3.1

4.6

3.2

<.0001

Median

4.0

4.0

DCI Score (N,%)

0

50

11.0%

896

16.1%

1

81

17.8%

852

15.4%

2

60

13.2%

787

14.2%

3+

265

58.1%

3014

54.3%

Estimated Years with COPD (Mean, SD)

3.2

1.15

2.4

1.55

Comorbidities (N,%)

Anxiety

11

2.4%

713

12.8%

<.0001

Cardiovascilar disease

14

3.1%

637

11.5%

<.0001

COVID-19

31

6.8%

1392

25.1%

<.0001

Diabetes

158

34.6%

1972

35.5%

<.0001

GERD

19

4.2%

591

10.7%

0.4823

Hypertension

30

6.6%

1287

23.2%

<.0001

Tobacco dependence

28

6.1%

1514

27.3%

0.2536

Presence of Cognitive or Motor Disorder (N,%)

15

3.3%

737

13.3%

<.0001

COPD Treatment (N,%)

Inhaled corticosteroids (ICS)

159

34.9%

467

8.4%

<.0001

Long-acting beta agonists (LABA)

149

32.7%

171

3.1%

<.0001

Long-acting muscarinic antagonists (LAMA)

59

12.9%

274

4.9%

<.0001

ICS/LABA

126

27.6%

1959

35.3%

<.0001

Leukotriene modifiers

73

16.0%

465

8.4%

<.0001

Macrolide antibiotics

207

45.4%

2001

36.1%

0.0010

Methylxanthines

20

4.4%

47

0.8%

<.0001

PDE-4 Inhibitors

26

5.7% 

120

2.2%

<.0001

Short-acting beta agonists (SABA)

342

75.0%

3,650

65.8%

0.0041

Short-acting muscarinic antagonists (SAMA)

63

13.8%

376

6.8%

<.0001

Systemic corticosteroids

368

80.7%

3,570

64.3%

<.0001

Oxygen therapy

262

57.5%

1,607

29.0%

<.0001

Nebulizer Use

181

39.7%

1,976

35.6%

0.2778

Total Baseline Healthcare Costs (Mean,SD)

 $45,577

 $44,473

 $42,580

 $45,180 

<.0001

Median costs

 $31,930 

 $26,558

Conclusions

Revefenacin patients tended to be older and potentially suffering from more severe disease based on baseline treatment patterns data. Thus, analyses revealed that the tiotropium and revefenacin treatment groups likely draw from different segments of the COPD population and may have unique clinical needs.

Methodology

We used two de-identified claims databases for this retrospective analysis; the 100% Medicare FFS database through a research-focused data use agreement with the Centers for Medicare & Medicaid Services, and the MORE2 Registry® database, which is a real-world, multi-payer dataset comprised of medical and pharmacy claims. Patients with an inpatient hospitalization with an admitting diagnosis of COPD between November 9, 2018 and September 30, 2020 (Medicare FFS database) or between November 9, 2018 and July 31, 2021 (MORE2 database) and prescribed revefenacin or tiotropium within 90 days post-hospitalization (index treatment) were included. The index hospitalization was set to the date of discharge of the earliest hospitalization with an admitting diagnosis of COPD, which was also followed by a prescription for tiotropium or revefenacin. The earliest fill for revefenacin or tiotropium treatment post discharge was set as the treatment index date. In addition, patients were required to be >40 years of age on the treatment index date and have 12 months of continuous enrollment preceding the treatment index date and ≥ 90 days of continuous enrollment following the treatment index date. Demographics were assessed for all individuals on the treatment index date, while clinical characteristics were measured during the 12-month baseline period.

Notes

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