A 4-Year Retrospective Claims Analysis of Oral Corticosteroid Use and Health Conditions in Newly Diagnosed Medicare FFS Patients with COPD

Figures & data

Table 1 Potential Adverse Health Conditions and Events of Interest

Chronic Conditions	Acute Events
Atrial fibrillation/flutter	Gastrointestinal bleeding/peptic ulcers
Avascular necrosis	Myocardial infarction
Cardiomyopathy	Osteoporotic fracture
Cardiovascular disease	Other infections that may be associated with immunosuppression
Cataracts	Sepsis
Chronic kidney disease	Stroke
Depression/anxiety
Dyslipidemia
Dyspepsia
Glaucoma
Heart failure
Hypertension
Metabolic syndrome/pre-diabetes
Mycobacterium avium infection
Non-healing extremity ulcer
Obesity
Osteoporosis
Peripheral arterial disease
Psychosis
Sleep apnea
Sleep disorders (non-apnea)
Thromboembolism
Type 2 diabetes

Table 2 Patient Characteristics for Total Study Population (N=183,637)

Characteristic	n	%
Age at index
Aged 40–64	42,836	23.3%
Aged 65–69	27,724	15.1%
Aged 70–74	36,826	20.1%
Aged 75–79	28,544	15.5%
Aged 80+	47,707	26.0%
Mean age	71.8
Median age	72
Sex
Female	101,471	55.3%
Male	82,166	44.7%
Low Income Subsidy eligibility
Non low-income subsidy eligible at index	95,663	52.1%
Low-income subsidy eligible at index	87,974	47.9%
Medicaid-Medicare dual eligibility
Non dual-eligible at index	107,499	58.5%
Dual-eligible at index	76,138	41.5%
Metropolitan Statistical Area (MSA)
Residence in an MSA	133,448	72.7%
Residence outside an MSA	50,189	27.3%
Race
White	155,704	84.8%
Black	17,248	9.4%
Other	9,876	5.4%
Unknown	809	0.4%
Follow-Up Time in Study Population
At least 12 months post-index	183,637	100.0%
At least 24 months post-index	142,852	77.8%
At least 36 months post-index	111,577	60.8%
At least 48 months post-index	88,029	47.9%
Mean follow-up post-index (months)	37
Median follow-up post-index (months)	47

Table 3 OCS Use Patterns

	1–12 Months Post-Index		1–24 Months Post-Index		1–36 Months Post-Index		1–48 Months Post-Index
OCS Use within Time Period	n/Mean	%/Median	n/Mean	%/Median	n/Mean	%/Median	n/Mean	%/Median
Patients included in analysis	183,637	100%	183,637	100%	183,637	100%	183,637	100%
Average patient months in period per patient	12		23		31		37
Cumulative OCS Dose^a
0 mg	149,317	81%	133,854	73%	124,465	68%	118,112	64%
>0 to 500 mg	29,091	16%	39,400	21%	44,563	24%	47,612	26%
>500 to 1000 mg	3,752	2%	6,927	4%	9,249	5%	10,930	6%
>1000 to 1500 mg	784	0%	1,679	1%	2,557	1%	3,209	2%
>1500 mg	693	0%	1,777	1%	2,803	2%	3,774	2%
Mean/median mg among >0 mg patients	343	210	422	250	481	280	526	300
Number of OCS Prescriptions
0	149,317	81%	133,854	73%	124,465	68%	118,112	64%
1 Fill	24,433	13%	30,807	17%	33,367	18%	34,658	19%
2 Fills	6,251	3%	10,435	6%	12,755	7%	14,222	8%
3 Fills	1,948	1%	4,040	2%	5,717	3%	6,870	4%
≥4 Fills	1,688	1%	4,501	2%	7,333	4%	9,775	5%
Pattern of OCS use
No OCS use	149,317	81%	133,854	73%	124,465	68%	118,112	64%
Single episode	26,649	15%	33,627	18%	36,406	20%	37,819	21%
Sporadic episodes: at least 365 days apart	> 0	~0%	2,706	1%	5,128	3%	7,068	4%
Infrequent episodes: 182–364 days apart	1,816	1%	3,055	2%	3,373	2%	3,450	2%
Moderately infrequent episodes: 90–181 days apart	1,669	1%	2,164	1%	2,238	1%	2,263	1%
Frequent episodes: 15–89 days apart	2,982	2%	3,596	2%	3,796	2%	3,855	2%
Mixed: gaps between episodes are a mixture of the patterns listed above	> 1,194	~1%	4,635	3%	8,231	4%	11,070	6%

Notes: Results may be approximated with “>” or “~” in accordance with the CMS data use agreement. ^aCumulative OCS dose is standardized to prednisolone equivalents.

Abbreviations: OCS, oral corticosteroid; mg, milligram; CMS, Centers for Medicare & Medicaid Services.

Figure 1 Cumulative distribution of OCS episodes by days supplied.

Abbreviation: OCS, oral corticosteroid.

Table 4 COPD Exacerbations by Severity for Initial 12-Month Period and by Cumulative Prednisolone Exposure Over 48-Month Period

% of Patients with COPD Exacerbations in the Specified Time Period	Months 1–12 Post-Index	Cumulative Prednisolone Equivalent OCS Use in Months 1–48 Post-Index
	All Patients	All Patients	0 mg	>0-500 mg	>500-1000 mg	>1000-1500 mg	>1500 mg
Patients included in analysis	183,637	183,637	118,112	47,578	10,942	3,214	3,791
Average patient months in period per patient	12	37	36	39	41	41	41
COPD Hospitalizations
% of patients with no exacerbations	89%	80%	85%	75%	67%	61%	53%
% of patients with 1 exacerbation	9%	14%	12%	18%	20%	22%	24%
% of patients with 2 exacerbations	1%	3%	2%	5%	7%	9%	11%
% of patients with at least 3 exacerbations	>0%	2%	1%	2%	5%	8%	13%
Hospitalization or ED COPD Exacerbations
% of patients with no exacerbations	83%	72%	80%	61%	51%	46%	39%
% of patients with 1 exacerbation	14%	19%	15%	27%	26%	24%	25%
% of patients with 2 exacerbations	2%	5%	3%	8%	12%	14%	13%
% of patients with 3 exacerbations	1%	3%	1%	4%	11%	16%	23%
Hospitalization, ED, or Ambulatory COPD Exacerbations
% of patients with no exacerbations	66%	48%	60%	29%	17%	13%	13%
% of patients with 1 exacerbation	25%	26%	25%	32%	23%	17%	14%
% of patients with 2 exacerbations	6%	12%	9%	18%	19%	16%	12%
% of patients with at least 3 exacerbations	3%	14%	7%	20%	41%	54%	61%

Notes: Results may be approximated with “>” or “~” in accordance with the CMS data use agreement.

Abbreviations: COPD, chronic obstructive pulmonary disease; OCS, oral corticosteroid; ED, emergency department; mg, milligram; CMS, Centers for Medicare & Medicaid Services.

Table 5 Comorbidities and Potential Adverse Health Outcomes Identified in the Baseline and Post-Index Periods

Health Outcome	Patients with Chronic Health Condition or Acute Event in Baseline Period		Patients with Incident Health Outcome in 1–48 Months Post-Index
	n	%	n	%
Health Conditions/Events Examined	29		29
Cardiovascular	153,722	83.7%	102,315	55.7%
Chronic Condition	153,639	83.7%	99,953	54.4%
Atrial fibrillation/flutter	22,463	12.2%	20,641	11.2%
Cardiomyopathy	7,966	4.3%	8,904	4.8%
Cardiovascular disease	51,603	28.1%	28,061	15.3%
Dyslipidemia	109,808	59.8%	24,326	13.2%
Heart failure	17,865	9.7%	30,916	16.8%
Hypertension	123,904	67.5%	19,596	10.7%
Non-healing extremity ulcer	11,323	6.2%	14,859	8.1%
Peripheral arterial disease	26,813	14.6%	24,365	13.3%
Thromboembolism	5,837	3.2%	8,576	4.7%
Event	5,046	2.7%	13,075	7.1%
Myocardial infarction	2,349	1.3%	6,560	3.6%
Stroke	2,774	1.5%	6,880	3.7%
Metabolic	67,953	37.0%	43,677	23.8%
Chronic Condition	67,953	37.0%	43,677	23.8%
Metabolic syndrome/pre-diabetes	1,051	0.6%	4,566	2.5%
Obesity	32,182	17.5%	31,442	17.1%
Type 2 diabetes	50,571	27.5%	12,684	6.9%
Bone	28,799	15.7%	36,992	20.1%
Chronic Condition	19,462	10.6%	18,122	9.9%
Avascular necrosis	667	0.4%	1,099	0.6%
Osteoporosis	18,917	10.3%	17,192	9.4%
Event	13,520	7.4%	24,599	13.4%
Osteoporotic fracture	13,520	7.4%	24,599	13.4%
Renal	25,542	13.9%	20,020	10.9%
Chronic Condition	25,542	13.9%	20,020	10.9%
Chronic kidney disease	25,542	13.9%	20,020	10.9%
Gastrointestinal	58,170	31.7%	50,400	27.4%
Chronic Condition	53,122	28.9%	36,722	20.0%
Dyspepsia	53,122	28.9%	36,722	20.0%
Event	11,034	6.0%	19,775	10.8%
Gastrointestinal bleeding/peptic ulcers	11,034	6.0%	19,775	10.8%
Ophthalmological	65,186	35.5%	43,686	23.8%
Chronic Condition	65,186	35.5%	43,686	23.8%
Cataracts	51,819	28.2%	36,777	20.0%
Glaucoma	25,754	14.0%	12,094	6.6%
Sleep	30,665	16.7%	24,108	13.1%
Chronic Condition	30,665	16.7%	24,108	13.1%
Sleep apnea	16,987	9.3%	11,039	6.0%
Sleep disorders (non-apnea)	16,747	9.1%	14,918	8.1%
Infection	86,987	47.4%	140,732	76.6%
Chronic Condition	> 170	~0%	338	0.2%
Mycobacterium avium infection	> 170	~0%	338	0.2%
Event	86,927	47.3%	140,696	76.6%
Other infections that may be associated with SCS-related immunosuppression	86,482	47.1%	140,012	76.2%
Sepsis	7,205	3.9%	25,565	13.9%
Mental Health	66,297	36.1%	35,173	19.2%
Chronic Condition	66,297	36.1%	35,173	19.2%
Depression/anxiety	59,467	32.4%	27,284	14.9%
Psychosis	17,313	9.4%	10,658	5.8%

Notes: Results may be approximated with “>” or “~” in accordance with the CMS data use agreement.

Abbreviation: CMS, Centers for Medicare & Medicaid Services.

Figure 2 Potential adverse health outcomes in months 1–48 post-index by OCS exposure.

Abbreviations: OCS, oral corticosteroid; mg, milligram.

Figure 3 Hazard Ratios for univariate regressions by cumulative prednisolone equivalent OCS dose in mg (vs 0 mg) for (A) heart failure and (B) cardiovascular disease.^a

Notes: ^aDotted lines reflect 95% confidence interval.

Abbreviations: OCS, oral corticosteroid; mg, milligram.

Table 6 Multivariable Regression Results for Cumulative OCS Dose

Health Outcomes	Hazard Ratio
	Cumulative Prednisolone Equivalent OCS Dose Grouping (vs 0 mg)
	>0-250 mg	>250-500 mg	>500-750 mg	>750-1000 mg	>1000-1500 mg	>1500 mg
Cardiovascular disease	0.897*	0.895*	1.040	1.102	1.155	1.497*
Heart failure	0.884*	0.986	1.108*	1.116	1.259*	1.531*
Peripheral arterial disease	0.863*	0.850*	0.899	0.838	0.917	1.070
Obesity	1.013	1.126*	1.196*	1.201*	1.195*	1.311*
Osteoporotic fracture	0.977	1.006	1.058	0.975	1.086	1.341*
Dyspepsia	0.929*	1.015	1.089	1.029	1.443*	1.462*
Cataracts	1.009	1.068*	1.093*	1.160*	1.209*	1.334*
Other infections that may be associated with SCS-related immunosuppression	1.034*	1.061*	1.185*	1.207*	1.099	1.443*
Sepsis	0.936*	1.005	0.997	1.098	1.140	1.808*
Depression/anxiety	0.876*	0.935	1.070	0.950	1.186	1.282*

Notes: *at least 2.5 estimated standard deviations away from a 1.0 hazard ratio. Numbers in italics are less than 2.5 estimated standard deviations away from a 1.0 hazard ratio.

Abbreviations: OCS, oral corticosteroid; mg, milligram.

Table 7 Multivariable Regression Results for Cumulative OCS Dose – Excluding Patients with COPD Hospitalizations in the 48 Months Post-Index (Includes 80% of Study Population)

	Cumulative Prednisolone Equivalent OCS Dose Grouping (vs 0 mg)
Patient Count	>0-250 mg	>250-500 mg	>500-750 mg	>750-1000 mg	>1000-1500 mg	>1500 mg
Full Study Population	118,112	47,578	7,186	3,756	3,214	3,791
No COPD Hospitalizations	100,733	35,575	4,915	2,469	1,952	2,008
% in Subpopulation	85%	75%	68%	66%	61%	53%
Health Outcomes	Hazard Ratio
Cardiovascular disease	0.871*	0.865*	0.942	1.059	0.947	0.879
Heart failure	0.856*	0.894*	0.843*	0.933	0.872	1.101
Peripheral arterial disease	0.851*	0.823*	0.797*	0.864	0.843	0.793
Obesity	1.049	1.138*	1.216*	1.289*	1.238	1.216
Osteoporotic fracture	0.963	0.983	1.049	0.914	1.009	1.213
Dyspepsia	0.978	0.986	1.040	1.025	1.336*	1.207
Cataracts	1.015	1.073*	1.098	1.147	1.252*	1.356*
Other infections that may be associated with SCS-related immunosuppression	1.071*	1.070*	1.178*	1.194*	0.961	1.377*
Sepsis	0.840*	0.770*	0.615*	0.574*	0.691	1.016
Depression/anxiety	0.884*	0.909*	1.040	0.884	1.155	1.156

Notes: *at least 2.5 estimated standard deviations away from a 1.0 hazard ratio. Numbers in italics are less than 2.5 estimated standard deviations away from a 1.0 hazard ratio.

Abbreviations: COPD, chronic obstructive pulmonary disease; OCS, oral corticosteroid; mg, milligram.

Figure 4 Parameter (as percent of the total number of outcomes analyzed) and 95% confidence interval for the increase in specified health outcomes associated with >1000 mg vs 0 mg prednisolone equivalent OCS dose in the 48 months post-index.

Abbreviations: OCS, oral corticosteroid; mg, milligram.