Retrospective analysis to describe associations between tumor necrosis factor alpha inhibitors and COPD-related hospitalizations

Figures & data

Figure 1 Patient selection.

Abbreviations: AS, ankylosing spondylitis; DMARD, disease-modifying antirheumatic drug; PsA, psoriatic arthritis; PsO, psoriasis; RA, rheumatoid arthritis; TNFi, tumor necrosis factor-alpha inhibitor.

Table 1 Patient demographic characteristics

Demographic characteristics	All patients	TNFi only	TNFi + DMARD	DMARD only	Untreated
	N=40,687	n=3,583	n=7,337	n=14,420	n=15,347
Age (years), mean (SD)	59.8 (13.9)	55.0 (13.5)	57.3 (12.0)	61.9 (13.1)	60.2 (15.0)
Age group (years), n (%)
18–34	1,720 (4.2)	258 (7.2)	280 (3.8)	380 (2.6)	802 (5.2)
35–44	3,531 (8.7)	497 (13.9)	739 (10.1)	914 (6.3)	1,381 (9.0)
45–54	8,240 (20.3)	947 (26.4)	1,769 (24.1)	2,548 (17.7)	2,976 (19.4)
55–64	13,329 (32.8)	1,094 (30.5)	2,702 (36.8)	4,829 (33.5)	4,704 (30.7)
≥65	13,867 (34.1)	787 (22.0)	1,847 (25.2)	5,749 (39.9)	5,484 (35.7)
Female, n (%)	27,373 (67.3)	2,087 (58.3)	5,370 (73.2)	10,283 (71.3)	9,633 (62.8)
Geographic region, n (%)
Northeast	6,280 (15.4)	538 (15.0)	950 (13.0)	2,080 (14.4)	2,712 (17.7)
North Central	12,556 (30.9)	1,002 (28.0)	2,166 (29.5)	4,704 (32.6)	4,684 (30.5)
South	14,891 (36.6)	1,419 (39.6)	2,919 (39.8)	5,202 (36.1)	5,351 (34.9)
West	6,588 (16.2)	587 (16.4)	1,243 (16.9)	2,323 (16.1)	2,435 (15.9)
Unknown	372 (0.9)	37 (1.0)	59 (0.8)	111 (0.8)	165 (1.1)
Insurance plan type, n (%)
Capitated	36,967 (90.9)	3,259 (91.0)	6,649 (90.6)	13,084 (90.7)	13,975 (91.1)
Non-capitated	3,720 (9.1)	324 (9.0)	688 (9.4)	1,336 (9.3)	1,372 (8.9)
Days of follow-up, mean (SD)	882 (614)	888 (591)	1,073 (648)	905 (609)	767 (580)

Abbreviations: DMARD, disease-modifying antirheumatic drug; SD, standard deviation; TNFi, tumor necrosis factor inhibitors.

Table 2 Patient clinical characteristics

Clinical characteristics	All patients	TNFi only	TNFi + DMARD	DMARD only	Untreated
	N=40,687	n=3,583	n=7,337	n=14,420	n=15,347
Deyo-Charlson Comorbidity Index, mean (SD)	1.5 (1.6)	1.1 (1.4)	1.4 (1.2)	1.7 (1.5)	1.5 (1.8)
Baseline comorbid conditions, n (%)
Anxiety	2,990 (7.3)	260 (7.3)	474 (6.5)	913 (6.3)	1,343 (8.8)
Asthma	5,209 (12.8)	424 (11.8)	922 (12.6)	1,963 (13.6)	1,900 (12.4)
Congestive heart failure	2,714 (6.7)	137 (3.8)	260 (3.5)	1,011 (7.0)	1,306 (8.5)
Depression	4,220 (10.4)	342 (9.5)	755 (10.3)	1,422 (9.9)	1,701 (11.1)
Hyperlipidemia	11,423 (28.1)	899 (25.1)	1,658 (22.6)	3,938 (27.3)	4,928 (32.1)
Hypertension	18,314 (45.0)	1,397 (39.0)	2,873 (39.2)	6,678 (46.3)	7,366 (48.0)
Obesity	2,138 (5.3)	194 (5.4)	320 (4.4)	671 (4.7)	953 (6.2)
Osteoarthritis	5,992 (14.7)	441 (12.3)	1,101 (15.0)	2,240 (15.5)	2,210 (14.4)
Osteoporosis	3,060 (7.5)	179 (5.0)	576 (7.9)	1,316 (9.1)	989 (6.4)
Pneumonia	1,606 (3.9)	98 (2.7)	216 (2.9)	623 (4.3)	669 (4.4)
Type 2 diabetes	7,179 (17.6)	594 (16.6)	1,069 (14.6)	2,495 (17.3)	3,021 (19.7)
Pre-index TNFi indicated condition, n (%)
Rheumatoid arthritis	23,101 (56.8)	1,514 (42.3)	5,747 (78.3)	10,165 (70.5)	5,675 (37.0)
Psoriasis	9,633 (23.7)	1,425 (39.8)	768 (10.5)	1,351 (9.4)	6,089 (39.7)
Psoriatic arthritis	3,002 (7.4)	675 (18.8)	817 (11.1)	753 (5.2)	757 (4.9)
Ankylosing spondylitis	1,057 (2.6)	260 (7.3)	172 (2.3)	158 (1.1)	467 (3.0)
Pre-index concomitant medications, n (%)
Oral/self-administered corticosteroids	18,042 (44.3)	1,272 (35.5)	4,049 (55.2)	7,776 (53.9)	4,945 (32.2)
IV corticosteroids	14,455 (35.5)	1,147 (32.0)	3,064 (41.8)	5,387 (37.4)	4,857 (31.6)
Inhaled corticosteroids	9,693 (23.8)	814 (22.7)	1,940 (26.4)	3,784 (26.2)	3,155 (20.6)
SABA	7,797 (19.2)	664 (18.5)	1,513 (20.6)	3,059 (21.2)	2,561 (16.7)
LABA	4,079 (10.0)	342 (9.5)	825 (11.2)	1,622 (11.2)	1,290 (8.4)
Long-acting anti-muscarinics	1,092 (2.7)	90 (2.5)	192 (2.6)	455 (3.2)	355 (2.3)
Antibiotics	28,513 (70.1)	2,461 (68.7)	5,522 (75.3)	10,678 (74.1)	9,852 (64.2)
Theophylline	211 (0.5)	13 (0.4)	36 (0.5)	88 (0.6)	74 (0.5)
Ipratropium bromide	2,032 (5.0)	142 (4.0)	343 (4.7)	846 (5.9)	701 (4.6)
Other biologics	113 (0.3)	3 (0.1)	14 (0.2)	68 (0.5)	28 (0.2)
Physician specialty at index COPD diagnosis, n (%)
Rheumatologist	15,152 (37.2)	1,356 (37.8)	3,960 (54.0)	6,589 (45.7)	3,247 (21.2)
Dermatologist	11,306 (27.8)	1,375 (38.4)	1,464 (20.0)	2,966 (20.6)	5,501 (35.8)
Pulmonologist	3,521 (8.7)	294 (8.2)	628 (8.6)	1,431 (9.9)	1,168 (7.6)

Abbreviations: DMARD, disease-modifying antirheumatic drug; IV, intravenous; LABA, long-acting beta-agonist; SABA, short-acting beta-agonist; SD, standard deviation; TNFi, tumor necrosis factor inhibitors.

Figure 2 Unadjusted probability of first COPD-related hospitalization by days after starting treatment.

Abbreviations: TNFi, tumor necrosis factor inhibitors; IP, inpatient.

Figure 3 Adjusted^a probability of first COPD-related hospitalization by days after starting treatment.

Notes: ^aAdjusted for age, gender, region, baseline CCI, baseline diagnosis of: RA, PsA, PsO, AS, hypertension, pneumonia, asthma, Type 2 diabetes, obesity, depression, hyperlipidemia, osteoporosis, congestive heart failure, anxiety, and baseline use of: non-biologic DMARD, oral/self-administered corticosteroids, inhaled corticosteroids, physician-administered corticosteroids, LABA, SABA, long-acting anti-muscarinics, ipratropium bromide, antibiotics, and baseline biologic use (ETA, ADA, INF, GOL, CTZ, or other).
Abbreviations: AS, ankylosing spondylitis; CCI, Deyo-Charlson Comorbidity Index; DMARD, disease-modifying antirheumatic drug; PsA, psoriatic arthritis; PsO, psoriasis; RA, rheumatoid arthritis; LABA, long-acting beta-agonist; SABA, short-acting beta-agonist; TNFi, tumor necrosis factor inhibitors; IP, inpatient; ETA, etanercept; ADA, adalimumab; INF, infliximab; GOL, golimumab; CTZ, certolizumab.

Figure 4 Hazard ratio of COPD-related hospitalization or ER visits during 3-year follow-up period.

Note: Hazard ratios with 95% confidence intervals.

Abbreviations: ER, emergency room; TNFi, tumor necrosis factor inhibitors.

Figure 5 Hazard ratio of COPD-related hospitalization or ER visits during 3-year follow-up period, all ages combined.

Notes: Referent for medication use is no pharmacy claims during pre-index period. Referent for comorbidities is no diagnoses during pre-index period. Referent for comorbidity score is 0 during pre-index period. Hazard ratios with 95% confidence intervals.
Abbreviations: DMARD, disease-modifying antirheumatic drug; ER, emergency room; IV, intravenous.

Table S1 Adjusted relative risk of a COPD-related IP admission or ER visit by age

Cohort	All ages		18–44 years		45–54 years		55–64 years		≥65 years
	HR	P-value	HR	P-value	HR	P-value	HR	P-value	HR	P-value
TNFi only	1.003	0.97	0.530	0.09	0.999	0.99	1.175	0.24	1.002	0.99
TNFi and DMARD	0.678	<0.0001	0.877	0.57	0.731	0.02	0.619	<0.0001	0.700	<0.0001
DMARD only	1.000	–	1.000	–	1.000	–	1.000	–	1.000	–

Note: ‘–’ indicates referent.

Abbreviations: DMARD, disease-modifying antirheumatic drug; ER, emergency room, HR, hazard ratio; IP, inpatient; TNFi, tumor necrosis factor-alpha inhibitor.