Effects of non-medical switching on outcomes among patients prescribed tumor necrosis factor inhibitors

Figures & data

Figure 1. Selection process. (A) NMS cohort. (B) Control cohort. Abbreviations. AS, ankylosing spondylitis; CD, Crohn’s disease; ED, emergency department; NLP, natural language processing; NMS, non-medical switch; Ps, psoriasis; PsA, psoriatic arthritis; RA, rheumatoid arthritis; TNF, tumor necrosis factor; UC, ulcerative colitis.

Table 1. Patient characteristics.

Characteristic^a	Control	NMS	p value^b,^c
N	4804	158
Demographics
Female	73.4 (3528)	72.2 (114)	.72
Median (IQR) age	54 (16)	56 (17)	.20
Race			.56
White	79.4 (3813)	81.0 (128)
African American	2.8 (135)	3.2 (5)
Asian	1.5 (72)	2.5 (4)
Other/unknown	16.3 (784)	13.3 (21)
US Census region			.60
Northeast	9.7 (466)	8.2 (13)
South	33.9 (1628)	38.6 (61)
Midwest	31.4 (1508)	30.4 (48)
West	22.2 (1068)	21.5 (34)
Unknown	2.8 (134)	1.3 (2)
Insurance type			.035
Commercial	41.5 (1992)	37.3 (59)
Medicare	11.4 (549)	8.9 (14)
Medicaid	2.6 (126)	1.9 (3)
Other	8.1 (388)	3.2 (5)
Uninsured	1.5 (71)	1.9 (3)
Unknown	15.4 (741)	22.8 (36)
Missing	19.5 (937)	24.1 (38)
ZIP code level median (IQR) household income	40,383 (20,598)	37,892 (11,401)	.002
ZIP code level percentage (IQR) residents with college education or higher	23 (12)	21.5 (10)	.091
Calendar year of index date			<.001
2007	8.9 (429)	1.9 (3)
2008	15.9 (764)	5.1 (8)
2009	15.8 (761)	10.1 (16)
2010	13.2 (634)	16.5 (26)
2011	14.8 (709)	17.1 (27)
2012	19.1 (919)	29.8 (47)
2013	12.2 (588)	19.6 (31)
Clinical characteristics
Immune disorder			.015
Rheumatoid arthritis	75.6 (3630)	65.2 (103)
Crohn’s disease	3.1 (148)	5.1 (8)
Psoriasis	8.3 (398)	8.9 (14)
Ulcerative colitis	0.1 (7)	0.6 (1)
Psoriatic arthritis	8.1 (387)	12.7 (20)
Ankylosing spondylitis	2.2 (106)	5.1 (8)
Missing	2.7 (128)	2.5 (4)
Initial medication			<.001
Etanercept	51.2 (2458)	37.3 (59)
Adalimumab	35.7 (1713)	37.3 (59)
Infliximab	10.9 (525)	12.7 (20)
Certolizumab pegol	0.9 (43)	2.5 (4)
Golimumab	1.4 (65)	10.1 (16)
Member of integrated delivery system	36.1 (1736)	41.8 (66)	.15

^a Findings expressed as % (N) unless noted otherwise.

^b Statistical significance between cohorts was evaluated by Pearson’s χ² test for categorical variables.

^c Statistical significance between cohorts was evaluated by non-parametric two-sample test of equality of medians for continuous variables.

Abbreviations. IQR, interquartile range; NMS, non-medical switch. ZIP Code is a small, contiguous geographic area represented by a single postal code. Integrated delivery system is network of health care organizations under common ownership.

Table 2. Health care use.

Endpoint	Control	NMS	Difference	95% CI	p value
Unadjusted percentages^a
30 days
N^b	4735	153
Ambulatory office or clinic visit	31.4 (1488)	54.3 (83)	22.8	(14.8, 30.8)	<.001
Emergency department usage	0.6 (30)	0.7 (1)	0.02	(−1.3, 1.3)	.98
Hospitalization	0.9 (41)	0.0 (0)	−0.9	(−1.1, −0.6)	<.001
90 days
N^b	4444	140
Ambulatory office or clinic visit	56.7 (2519)	82.1 (115)	25.5	(18.9, 32.0)	<.001
Emergency department usage	1.7 (77)	2.1 (3)	0.4	(−2.0, 2.8)	.74
Hospitalization	1.9 (85)	2.1 (3)	0.2	(−2.2, 2.7)	.85
365 days
N^b	3490	99
Ambulatory office or clinic visit	76.5 (2669)	98.0 (97)	21.5	(18.4, 24.6)	<.001
Emergency department usage	6.0 (208)	9.1 (9)	3.1	(−2.6, 8.9)	.28
Hospitalization	6.5 (227)	8.1 (8)	1.6	(−3.9, 7.0)	.57
Adjusted Percentages^c,^d
30 days
N^b	4735	153
Ambulatory office or clinic visit	31.7	46.4	14.8	(6.6, 22.9)	<.001
Emergency department usage	0.6	0.2	−0.4	(−1.6, 0.8)	.50
Hospitalization	0.9	−0.4	−1.3	(−1.9, −0.6)	<.001
90 days
N^b	4444	140
Ambulatory office or clinic visit	57.0	71.0	14.0	(5.9, 22.0)	<.001
Emergency department usage	1.8	1.3	−0.5	(−2.8, 1.9)	.69
Hospitalization	1.9	1.7	−0.3	(−2.9, 2.3)	.84
365 days
N^b	3490	99
Ambulatory office or clinic visit	76.8	87.8	11.1	(6.0, 16.1)	<.001
Emergency department usage	6.0	7.6	1.6	(−2.3, 5.5)	.43
Hospitalization	6.5	7.0	0.5	(−5.8, 6.7)	.89

^a Findings presented as unadjusted % (N).

^b N reflects patients with complete follow-up (based on EMR coverage) for the specified period.

^c Findings presented as adjusted %.

^d Proportions adjusted for match strata fixed effects and patient race, US Census region, insurance type, ZIP Code-level household income, ZIP Code-level percentage college educated, and calendar year of index date.

Abbreviations. CI, confidence interval; NMS, non-medical switch.

Table 3. Physician documentation of adverse clinical consequences.

Endpoint	Control	NMS	Difference	95% CI	p value
Unadjusted percentages^a
30 days
N^b	4735	153
Any adverse consequence	4.0 (187)	16.3 (25)	12.4	(6.5, 18.2)	<.001
Side effect	1.8 (87)	10.5 (16)	8.6	(3.8, 13.5)	<.001
Diminished efficacy	2.5 (118)	10.5 (16)	8.0	(3.1, 12.8)	<.001
90 days
N^b	4444	140
Any adverse consequence	9.4 (418)	36.4 (51)	27.0	(19.0, 35.0)	<.001
Side effect	5.1 (226)	25.7 (36)	20.6	(13.3, 27.9)	<.001
Diminished efficacy	5.8 (257)	22.1 (31)	16.4	(9.4, 23.3)	<.001
365 days
N^b	3490	99
Any adverse consequence	20.1 (700)	62.6 (62)	42.6	(32.9, 52.2)	<.001
Side effect	12.3 (429)	46.5 (46)	34.2	(24.3, 44.1)	<.001
Diminished efficacy	13.4 (468)	42.4 (42)	29.0	(19.2, 38.8)	<.001
Adjusted percentages^c,^d
30 days
N^b	4735	153
Any adverse consequence	4.0	13.8	9.8	(3.2, 16.3)	.003
Side effect	1.9	9.4	7.6	(2.5, 12.6)	.003
Diminished efficacy	2.5	9.0	6.5	(1.5, 11.4)	.011
90 days
N^b	4444	140
Any adverse consequence	9.6	31.6	22.0	(14.3, 29.7)	<.001
Side effect	5.1	23.7	18.5	(11.1, 26.0)	<.001
Diminished efficacy	5.9	19.1	13.2	(6.9, 19.6)	<.001
365 days
N^b	3490	99
Any adverse consequence	20.3	54.7	34.4	(26.8, 41.9)	<.001
Side effect	12.4	41.5	29.0	(20.6, 37.5)	<.001
Diminished efficacy	13.6	37.1	23.5	(13.5, 33.5)	<.001

^a Findings presented as unadjusted % (N).

^b N reflects patients with complete follow-up (based on EMR coverage) for the specified period.

^c Findings presented as adjusted %.

^d Proportions adjusted for match strata fixed effects and patient race, US Census region, insurance type, ZIP Code-level household income, ZIP Code-level percentage college educated, and calendar year of index date.

Abbreviations. CI, confidence interval; NMS, non-medical switch.

Table 4. Subsequent switching of anti-TNF biological therapy.

Endpoint^a	Control	NMS	Difference	95% CI	p value
Unadjusted percentages
30 days
N^b	4735	153
Any switch	0.8 (36)	5.2 (8)	4.5	(0.9, 8.0)	<.001
Switch related to adverse consequence	0.2 (7)	0.7 (1)	0.5	(−0.8, 1.8)	.44
90 days
N^b	4444	140
Any switch	2.6 (114)	12.1 (17)	9.6	(4.1, 15.0)	.001
Switch related to adverse consequence	0.7 (32)	2.1 (3)	1.4	(−1.0, 3.8)	.25
365 days
N^b	3490	99
Any switch	13.9 (484)	27.3 (27)	13.4	(4.6, 22.3)	.003
Switch related to adverse consequence	4.4 (152)	14.1 (14)	9.8	(2.9, 16.7)	.005
Adjusted percentages^c,^d
30 days
N^b	4735	153
Any switch	0.8	4.2	3.4	(0.2, 6.6)	.037
Switch related to adverse consequence	0.2	0.3	0.1	(−1.1, 1.4)	.87
90 days
N^b	4444	140
Any switch	2.6	10.2	7.6	(2.5, 12.7)	.003
Switch related to adverse consequence	0.7	1.5	0.7	(−1.5, 3.0)	.51
365 days
N^b	3490	99
Any switch	13.9	27.2	13.4	(5.3, 21.4)	.001
Switch related to adverse consequence	4.4	12.7	8.3	(1.8, 14.8)	.012

^a Findings presented as unadjusted % (N).

^b N reflects patients with complete follow-up (based on EMR coverage) for the specified period.

^c Findings presented as adjusted %.

^d Proportions adjusted for match strata fixed effects and patient race, US Census region, insurance type, ZIP Code-level household income, ZIP Code-level percentage college educated, and calendar year of index date.

Abbreviations. CI, confidence interval; NMS, non-medical switch.