Treatment persistence and maintenance dose titration among ulcerative colitis patients on biologics: a pooled study of three United States claim databases

Figures & data

Figure 1. Flow-chart for patient inclusion criteria. *IBM Study Period: January 1, 2014–September 30, 2018; Optum Study Period: January 1, 2014–March 31, 2019; IQVIA Study Period: January 1, 2014–December 31, 2018. **IBM Identification Period: January 1, 2015–September 30, 2017; Optum Identification Period: January 1, 2015–March 31, 2018; IQVIA Identification Period: January 1, 2015–December 31, 2017.

Table 1. Descriptive baseline characteristics for pooled bio-naïve and bio-experienced patients.

	Adalimumab		Golimumab		Infliximab		Vedolizumab
	Bio-naïve	Bio-experienced	Bio-naïve	Bio-experienced	Bio-naïve	Bio-experienced	Bio-naïve	Bio-experienced
Sample size	3,102	369	246	210	1,885	524	873	1,019
Age, mean (SD)	39.9 (12.9)	40.4 (13.0)	40.0 (13.2)	41.5 (12.6)	40.0 (13.5)	39.2 (12.8)	41.2 (12.6)	40.7 (12.6)
Age group, n (%)
18–34	1,151 (37.1%)	126 (34.1%)	91 (37.0%)	66 (31.4%)	697 (37.0%)	208 (39.7%)	286 (32.8%)	343 (33.7%)
35–54	1,437 (46.3%)	180 (48.8%)	112 (45.5%)	100 (47.6%)	845 (44.8%)	242 (46.2%)	440 (50.4%)	508 (49.9%)
55–64	514 (16.6%)	63 (17.1%)	43 (17.5%)	44 (21.0%)	343 (18.2%)	74 (14.1%)	147 (16.8%)	168 (16.5%)
Sex, n (%)
Male	1,906 (61.4%)	218 (59.1%)	142 (57.7%)	130 (61.9%)	1135 (60.2%)	328 (62.6%)	520 (59.6%)	652 (64.0%)
Female	1,196 (38.6%)	151 (40.9%)	104 (42.3%)	80 (38.1%)	750 (39.8%)	196 (37.4%)	353 (40.4%)	367 (36.0%)
US geographic region, n (%)
Northeast	541 (17.4%)	58 (15.7%)	24 (9.8%)	39 (18.6%)	324 (17.2%)	81 (15.5%)	169 (19.4%)	196 (19.2%)
North Central	763 (24.6%)	106 (28.7%)	59 (24.0%)	53 (25.2%)	572 (30.3%)	155 (29.6%)	236 (27.0%)	293 (28.8%)
South	1,312 (42.3%)	156 (42.3%)	123 (50.0%)	93 (44.3%)	719 (38.1%)	204 (38.9%)	337 (38.6%)	393 (38.6%)
West	432 (13.9%)	45 (12.2%)	36 (14.6%)	22 (10.5%)	232 (12.3%)	78 (14.9%)	122 (14.0%)	130 (12.8%)
Unknown	54 (1.7%)	4 (1.1%)	4 (1.6%)	3 (1.4%)	38 (2.0%)	6 (1.1%)	9 (1.0%)	7 (0.7%)
Charlson Comorbidity Index Score, mean (SD)	0.7 (1.2)	0.7 (1.2)	0.6 (1.0)	0.7 (1.2)	0.8 (1.5)	0.8 (1.1)	0.8 (1.4)	0.7 (1.2)
Baseline Comorbidities, n (%)
Anemia	823 (26.5%)	94 (25.5%)	60 (24.4%)	63 (30.0%)	655 (34.7%)	188 (35.9%)	237 (27.1%)	321 (31.5%)
Anxiety	441 (14.2%)	55 (14.9%)	27 (11.0%)	18 (8.6%)	258 (13.7%)	72 (13.7%)	123 (14.1%)	146 (14.3%)
Arthritis	150 (4.8%)	14 (3.8%)	12 (4.9%)	7 (3.3%)	78 (4.1%)	31 (5.9%)	49 (5.6%)	57 (5.6%)
Celiac disease	69 (2.2%)	8 (2.2%)	3 (1.2%)	6 (2.9%)	40 (2.1%)	17 (3.2%)	25 (2.9%)	25 (2.5%)
Chronic pain	89 (2.9%)	9 (2.4%)	8 (3.3%)	10 (4.8%)	59 (3.1%)	15 (2.9%)	18 (2.1%)	42 (4.1%)
Clostridium difficile	123 (4.0%)	18 (4.9%)	6 (2.4%)	10 (4.8%)	112 (5.9%)	37 (7.1%)	49 (5.6%)	77 (7.6%)
Depression	356 (11.5%)	52 (14.1%)	31 (12.6%)	30 (14.3%)	249 (13.2%)	80 (15.3%)	108 (12.4%)	130 (12.8%)
Diabetes	190 (6.1%)	28 (7.6%)	15 (6.1%)	22 (10.5%)	116 (6.2%)	32 (6.1%)	59 (6.8%)	67 (6.6%)
Fatigue	436 (14.1%)	55 (14.9%)	29 (11.8%)	34 (16.2%)	283 (15.0%)	76 (14.5%)	128 (14.7%)	142 (13.9%)
Obesity	274 (8.8%)	41 (11.1%)	21 (8.5%)	19 (9.0%)	175 (9.3%)	54 (10.3%)	81 (9.3%)	101 (9.9%)

Abbreviation. SD, Standard Deviation.

Figure 2. Unadjusted persistence rates among UC Patients during 12-month follow-up period using variable gap definition*. *Variable definition for ADA was 28 days; GOL was 56 days; IFX and VDZ was 112 days.

Table 2. Treatment patterns for pooled bio-naïve and bio-experienced patients.

Cohorts	Adalimumab^c		Golimumab		Infliximab		Vedolizumab
	Bio-naïve	Bio-experienced	Bio-naïve	Bio-experienced	Bio-naïve	Bio-experienced	Bio-naïve	Bio-experienced
Sample size	3,102	369	246	210	1,885	524	873	1,019
Main analysis – Using a variable gap definition^a
Persistence, n (%)	1,510 (48.7%)	182 (49.3%)	132 (53.7%)	100 (47.6%)	1,367 (72.5%)	368 (70.2%)	685 (78.5%)	796 (78.1%)
Discontinuation, n (%)	1,592 (51.3%)	187 (50.7%)	114 (46.3%)	110 (52.4%)	518 (27.5%)	156 (29.8%)	188 (21.5%)	223 (22.0%)
Switch, n (%)	564 (18.2%)	57 (15.4%)	54 (22.0%)	45 (21.4%)	214 (11.4%)	72 (13.7%)	53 (6.1%)	46 (4.5%)
Adalimumab	n/a	n/a	12 (4.9%)	4 (1.9%)	71 (3.8%)	5 (1.0%)	7 (0.8%)	11 (1.1%)
Golimumab	64 (2.1%)	11 (3.0%)	n/a	n/a	6 (0.3%)	5 (1.0%)	3 (0.3%)	8 (0.8%)
Infliximab	258 (8.3%)	6 (1.6%)	21 (8.5%)	15 (7.1%)	n/a	n/a	43 (4.9%)	27 (2.6%)
Vedolizumab	242 (7.8%)	40 (10.8%)	21 (8.5%)	26 (12.4%)	137 (7.3%)	62 (11.8%)	n/a	n/a
Restart of index biologic, n (%)	492 (15.9%)	58 (15.7%)	18 (7.3%)	9 (4.3%)	46 (2.4%)	7 (1.3%)	34 (3.9%)	30 (2.9%)
Discontinuation without restart or switch, n (%)	536 (17.3%)	72 (19.5%)	42 (17.1%)	56 (26.7%)	258 (13.7%)	77 (14.7%)	101 (11.6%)	147 (14.4%)
Sensitivity analysis – Using a fixed gap definition^b
Persistence, n (%)	1,969 (63.5%)	233 (63.1%)	144 (58.5%)	109 (51.9%)	1,303 (69.1%)	345 (65.8%)	658 (75.4%)	761 (74.7%)
Discontinuation, n (%)	1,133 (36.5%)	136 (36.9%)	102 (41.5%)	101 (48.1%)	582 (30.9%)	179 (34.2%)	215 (24.6%)	258 (25.3%)
Switch, n (%)	544 (17.5%)	59 (16.0%)	52 (21.1%)	45 (21.4%)	234 (12.4%)	78 (14.9%)	59 (6.8%)	51 (5.0%)
Restart of index biologic, n (%)	82 (2.6%)	12 (3.3%)	11 (4.5%)	2 (1.0%)	68 (3.6%)	10 (1.9%)	46 (5.3%)	46 (4.5%)
Discontinuation without restart or switch, n (%)	507 (16.3%)	65 (17.6%)	39 (15.9%)	54 (25.7%)	280 (14.9%)	91 (17.4%)	110 (12.6%)	161 (15.8%)
Medication Possession Ratio, mean (SD)	0.7 (0.3)	0.7 (0.3)	0.7 (0.3)	0.6 (0.3)	0.8 (0.4)	0.9 (0.4)	0.8 (0.3)	0.9 (0.4)
Patients with MPR ≥0.8, n (%)	1,783 (57.5%)	213 (57.7%)	129 (52.4%)	95 (45.2%)	1,170 (62.1%)	351 (67.0%)	562 (64.4%)	732 (71.8%)

^aA variable discontinuation gap of >28 days for ADA, 56 days for GOL, and >112 days for IFX and VDZ between the run-out date of one biologic and the start date of the next biologic claim (gap approximately two times the maintenance dosing interval) was used to define discontinuation.

^bA fixed gap of 90 days between the run-out date of one biologic and the start date of the next biologic claim was used to define discontinuation as sensitivity analysis.

^cAnother sensitivity analysis using a 60-day gap definition was evaluated for ADA. Among bio-naïve patients, 58.9% were persistent on ADA during the follow-up, 18.4% switched biologics, 5.1% of patients discontinued then restarted ADA, and 17.7% discontinued without restart or switch, whereas, for bio-experienced ADA patients, persistence was observed in 58.8%, 16.5% patients switched biologics, 5.4% patients discontinued then restarted ADA, and 19.2% discontinued without restart or switch.

Abbreviations. n/a, Not applicable; MPR, Medication Possession Ratio; SD, Standard Deviation.

Table 3. Dosing titration for pooled bio-naïve and bio-experienced patients.

Adalimumab (patients with ≥2 maintenance doses)	Doses	Bio-naïve	Bio-experienced
Sample size		2,599	217
50% Dose escalation	≥60 mg/2 weeks	337 (13.0%)	35 (16.1%)
100% Dose escalation	≥80 mg/2 weeks	82 (3.2%)	15 (6.9%)
50% Dose reduction	≤20 mg/2 weeks	21 (0.8%)	1 (0.5%)
Using 20% variation – patients on label	[32–48] mg/2 weeks	1,949 (75.0%)	158 (72.8%)
Using 20% variation – patients with dose escalation	>48 mg/2 weeks	497 (19.1%)	46 (21.2%)
Using 20% variation – patients with dose reduction	<32 mg/2 weeks	153 (5.9%)	13 (6.0%)
Golimumab (patients with ≥ 2 maintenance doses)	Doses	Bio-naïve	Bio-experienced
Sample size		187	77
50% Dose escalation	≥150 mg/4 weeks	3 (1.6%)	2 (2.6%)
100% Dose escalation	≥200 mg/4 weeks	2 (1.1%)	2 (2.6%)
50% Dose reduction	≤50 mg/4 weeks	1 (0.5%)	0 (0.0%)
Using 20% variation – patients on label	[80–120] mg/4 weeks	161 (86.1%)	67 (87.0%)
Using 20% variation – patients with dose escalation	>120 mg/4 weeks	8 (4.3%)	5 (6.5%)
Using 20% variation – patients with dose reduction	<80 mg/4 weeks	18 (9.6%)	5 (6.5%)
Vedolizumab (patients with ≥ 2 maintenance doses)	Doses	Bio-naïve	Bio-experienced
Sample size		582	365
50% Dose escalation	≥450 mg/8 weeks	47 (8.1%)	36 (9.9%)
100% Dose escalation	≥600 mg/8 weeks	2 (0.3%)	5 (1.4%)
50% Dose reduction	≤150 mg/8 weeks	0 (0.0%)	2 (0.6%)
Using 20% variation – patients on label	[240–360] mg/8 weeks	468 (80.4%)	283 (77.5%)
Using 20% variation – patients with dose escalation	>360 mg/8 weeks	95 (16.3%)	73 (20.0%)
Using 20% variation – patients with dose reduction	<240 mg/8 weeks	19 (3.3%)	9 (2.5%)

Data availability statement

Due to data user agreement between the authors and the data vendor, data cannot be made publicly available.