Switching and Discontinuation Patterns Among Patients Stable on Originator Infliximab Who Switched to an Infliximab Biosimilar or Remained on Originator Infliximab

Figures & data

Figure 1 Study design.

Abbreviations: AS, ankylosing spondylitis; CD, Crohn’s disease; IFX, infliximab; PsA, psoriatic arthritis; PsO, plaque psoriasis; RA, rheumatoid arthritis; UC, ulcerative colitis.

Figure 2 Patient selection.

Notes: ^aDiagnosis was identified using the following ICD-9 CM and ICD-10 CM codes: RA (ICD-9 CM code 714.0; ICD-10 CM code: M05.1-M05.9, M06), PsA (ICD-9 CM code 696.0; ICD-10 CM code: L40.5x), PsO (ICD-9 CM code 696.1; ICD-10 CM code: L40.0-L40.4, L40.8, L40.9), or AS (ICD-9 CM code 720.0; ICD-10 CM code: M45.x), CD (ICD-9 CM code 555.x; IDC-10 CM code K50.x), UC (ICD-9 CM code 556.x; IDC-10 CM code K51.x). ^bOriginator IFX was identified using the GPI code 5250504000 and HCPCS code J1745. IFX biosimilars were identified using the following codes: infliximab-abda (GPI code 5250504010; HCPCS code Q5102, Q5103), infliximab-dyyb (GPI code 5250504020; HCPCS code Q5102, Q5104), and infliximab-qbtx (GPI code 5250504060). ^cPregnancy was identified using the ICD-9 CM code V22.x and ICD-10 CM codes Z33.x and Z34.xx. ^dDiagnosis of heart failure was identified using the ICD-9-CM code 428.xx and ICD-10-CM code I50.x.

Abbreviations: AS, ankylosing spondylitis; CD, Crohn’s disease; GPI, Generic Product Identifier; HCPCS, Healthcare Common Procedure Coding System; ICD-9 CM/ICD-10 CM, international classification of disease, ninth/tenth revision, clinical modification; IFX, infliximab; PsA, psoriatic arthritis; PsO, plaque psoriasis; RA, rheumatoid arthritis; UC, ulcerative colitis.

Table 1 Baseline Demographic and Clinical Characteristics

	Matched Sample
	Prevalent Population			Incident Population
	Switchers	Continuers	Standardized Difference	Switchers	Continuers	Standardized Difference
	N=1109	N=3327		N=571	N=1713
Age in years, mean ± SD [median]	57.3 ± 16.3 [60.0]	56.9 ± 16.3 [60.0]	2.1%	56.5 ± 15.7 [57.0]	55.9 ± 15.4 [57.0]	4.2%
Female, n (%)	724 (65.3%)	2198 (66.1%)	1.6%	380 (66.5%)	1162 (67.8%)	2.7%
Year of index date, n (%)
2016	8 (0.7%)	24 (0.7%)	0.0%	4 (0.7%)	12 (0.7%)	0.0%
2017	408 (36.8%)	1249 (37.5%)	1.6%	169 (29.6%)	563 (32.9%)	7.1%
2018	456 (41.1%)	1410 (42.4%)	2.6%	274 (48.0%)	810 (47.3%)	1.4%
2019	237 (21.4%)	644 (19.4%)	5.0%	124 (21.7%)	328 (19.1%)	6.4%
US region, n (%)
South	309 (27.9%)	979 (29.4%)	3.5%	142 (24.9%)	428 (25.0%)	0.3%
Midwest	446 (40.2%)	1269 (38.1%)	4.3%	245 (42.9%)	713 (41.6%)	2.6%
Northeast	101 (9.1%)	324 (9.7%)	2.2%	51 (8.9%)	157 (9.2%)	0.8%
West	244 (22.0%)	743 (22.3%)	0.8%	132 (23.1%)	414 (24.2%)	2.5%
Unknown	9 (0.8%)	12 (0.4%)	5.9%	1 (0.2%)	1 (0.1%)	3.4%
Type of insurance plan, n (%)
Commercial	474 (42.7%)	1422 (42.7%)	0.0%	246 (43.1%)	722 (42.1%)	1.9%
Medicare	453 (40.8%)	1385 (41.6%)	1.6%	220 (38.5%)	673 (39.3%)	1.6%
Medicaid	149 (13.4%)	424 (12.7%)	2.1%	92 (16.1%)	272 (15.9%)	0.6%
Other	33 (3.0%)	96 (2.9%)	0.5%	13 (2.3%)	46 (2.7%)	2.6%
Specialty of physician prescribing IFX at index date, n (%)
Rheumatology	488 (44.0%)	1494 (44.9%)	1.8%	243 (42.6%)	750 (43.8%)	2.5%
Gastroenterology	301 (27.1%)	906 (27.2%)	0.2%	158 (27.7%)	474 (27.7%)	0.0%
Infectious diseases	12 (1.1%)	55 (1.7%)	4.9%	10 (1.8%)	38 (2.2%)	3.3%
Hematology/oncology	55 (5.0%)	122 (3.7%)	6.4%	32 (5.6%)	67 (3.9%)	8.0%
Oncology medical	20 (1.8%)	26 (0.8%)	9.1%	10 (1.8%)	13 (0.8%)	8.9%
Other/unknown	233 (21.0%)	724 (21.8%)	1.8%	118 (20.7%)	371 (21.7%)	2.4%
Prior history of CID, n (%)
RA	464 (41.8%)	1392 (41.8%)	0.0%	220 (38.5%)	660 (38.5%)	0.0%
PsA	151 (13.6%)	446 (13.4%)	0.6%	86 (15.1%)	272 (15.9%)	2.3%
PsO	87 (7.8%)	262 (7.9%)	0.1%	49 (8.6%)	156 (9.1%)	1.9%
AS	77 (6.9%)	226 (6.8%)	0.6%	47 (8.2%)	149 (8.7%)	1.7%
IBD	523 (47.2%)	1569 (47.2%)	0.0%	271 (47.5%)	813 (47.5%)	0.0%
CD	382 (34.4%)	1141 (34.3%)	0.3%	200 (35.0%)	596 (34.8%)	0.5%
UC	202 (18.2%)	587 (17.6%)	1.5%	107 (18.7%)	311 (18.2%)	1.5%
Quan-CCI, mean ± SD [median]	1.09 ± 1.30 [1.00]	1.09 ± 1.29 [1.00]	0.2%	1.10 ± 1.36 [1.00]	1.06 ± 1.27 [1.00]	2.8%
Baseline drug use, n (%)
Antidepressants	429 (38.7%)	1283 (38.6%)	0.3%	242 (42.4%)	747 (43.6%)	2.5%
NSAIDs	310 (28.0%)	947 (28.5%)	1.1%	163 (28.5%)	573 (33.5%)	10.6%
Corticosteroids	676 (61.0%)	1998 (60.1%)	1.8%	379 (66.4%)	1108 (64.7%)	3.6%
Biologics	1109 (100.0%)	3327 (100.0%)	0.0%	571 (100.0%)	1713 (100.0%)	0.0%
PDE4 inhibitors	3 (0.3%)	12 (0.4%)	1.6%	2 (0.4%)	9 (0.5%)	2.7%
Opioids	573 (51.7%)	1702 (51.2%)	1.0%	311 (54.5%)	961 (56.1%)	3.3%
Non-narcotic analgesics	51 (4.6%)	177 (5.3%)	3.3%	28 (4.9%)	85 (5.0%)	0.3%
DMARDs	641 (57.8%)	1962 (59.0%)	2.4%	343 (60.1%)	1082 (63.2%)	6.4%
Duration of treatment with originator IFX prior to index date days mean ± SD [median]	≥1073 ± 619 [991]	≥1035 ± 671 [893]	6.0%	762 ± 443 [628]	746 ± 480 [607]	3.6%
Place of service for index claim
Medical
Outpatient	1006 (90.7%)	3006 (90.4%)	1.2%	516 (90.4%)	1539 (89.8%)	1.8%
Inpatient	0 (0.0%)	0 (0.0%)	-	0 (0.0%)	0 (0.0%)	–
Emergency room	2 (0.2%)	9 (0.3%)	1.9%	1 (0.2%)	4 (0.2%)	1.3%
Other services	61 (5.5%)	197 (5.9%)	1.8%	37 (6.5%)	127 (7.4%)	3.7%
Pharmacy	30 (2.7%)	84 (2.5%)	1.1%	11 (1.9%)	29 (1.7%)	1.8%
Medical and pharmacy	10 (0.9%)	31 (0.9%)	0.3%	6 (1.1%)	14 (0.8%)	2.4%

Abbreviations: AS ankylosing spondylitis; CD Crohn’s disease; CID chronic inflammatory disease; DMARD disease modifying anti-rheumatic drug; IBD inflammatory bowel disease; IFX infliximab; NSAID non-steroidal anti-inflammatory drug; PDE4 phosphodiesterase-4; PsA psoriatic arthritis; PsO plaque psoriasis; Quan-CCI Quan-Charlson comorbidity index; RA, rheumatoid arthritis; SD, standard deviation; UC, ulcerative colitis; US, United States.

Figure 3 KM curves of (A) time to switch to another originator biologic among the prevalent population and (B) time to switch to another originator biologic among the incident population.

Note: *p<0.05. Abbreviations: CI, confidence interval; HR, hazard ratio; KM, Kaplan–Meier.

Figure 4 Proportion of patients switching to another originator biologic agent among switchers in the (A) prevalent population (N=1109; mean observation period of 337 days) and (B) incident population (N=571; mean observation period of 314 days).

Abbreviations: IFX, infliximab.

Table 2 KM Analysis of Time to Switch to Another Originator Biologic (Including Originator IFX) for the RA and IBD Subgroups

	0 Months	3 Months	6 Months	9 Months	12 Months	18 Months
RA subgroup
Prevalent population
KM rates (95% CI)
Switchers	100.00%	91.1% (88.0, 93.4)	83.4% (79.4, 86.8)	76.3% (71.5, 80.4)	70.3% (65.0, 75.0)	67.2% (61.5, 72.3)
Continuers	100.00%	97.3% (96.3, 98.1)	94.3% (92.7, 95.5)	92.2% (90.3, 93.7)	90.8% (88.7, 92.5)	89.2% (86.8, 91.2)
P-value of Log rank test	–	<0.001*	<0.001*	<0.001*	<0.001*	<0.001*
Incident population
KM rates (95% CI)
Switchers	100.00%	91.7% (86.9, 94.7)	83.4% (77.1, 88.1)	75.7% (68.2, 81.7)	73.8% (66.0, 80.1)	69.5% (60.5, 76.9)
Continuers	100.00%	96.2% (94.3, 97.4)	93.0% (90.5, 94.9)	90.0% (86.9, 92.4)	88.6% (85.2, 91.3)	82.4% (77.3, 86.5)
P-value of Log rank test	–	0.008*	<0.001*	<0.001*	<0.001 *	<0.001*
IBD subgroup
Prevalent population
KM rates (95% CI)
Switchers	100.00%	86.1% (82.6, 89.0)	80.9% (76.8, 84.4)	78.0% (73.6, 81.9)	73.3% (68.1, 77.8)	70.1% (64.2, 75.3)
Continuers	100.00%	97.9% (97.0, 98.5)	95.3% (93.9, 96.4)	93.7% (92.1, 95.0)	92.1% (90.2, 93.7)	90.3% (87.9, 92.2)
P-value of Log rank test	–	<0.001*	<0.001*	<0.001*	<0.001*	<0.001*
Incident population
KM rates (95% CI)
Switchers	100.00%	84.7% (79.4, 88.7)	80.4% (74.4, 85.0)	78.2% (71.9, 83.3)	72.3% (64.7, 78.6)	65.0% (54.8, 73.4)
Continuers	100.00%	96.6% (95.0, 97.7)	94.7% (92.6, 96.2)	92.9% (90.4, 94.7)	89.2% (86.0, 91.8)	87.6% (83.8, 90.6)
P-value of Log rank test	–	<0.001*	<0.001*	<0.001*	<0.001*	<0.001*

Note: *p<0.05.

Abbreviations: CI, confidence interval; IBD, inflammatory bowel disease; KM, Kaplan–Meier; RA, rheumatoid arthritis.

Figure 5 Switching and discontinuation rates for prevalent (switchers, N=1109; continuers, N=3327) and incident (switchers, N=571; continuers, N=1713) patients in the overall population, prevalent (switchers, N=464; continuers, N=1392) and incident (switchers, N=220; continuers, N=660) patients in the RA subgroup, as well as prevalent (switchers, N=523; continuers, N=1569) and incident (switchers, N=271; continuers, N=813) patients in the IBD subgroup.

Note: *p<0.05. Abbreviations: CI, confidence interval; HR, hazard ratio; IBD, inflammatory bowel disease; RA, rheumatoid arthritis.