Impact of adalimumab on disease burden in moderate-to-severe ulcerative colitis patients: The one-year, real-world UCanADA study

Table 1 Baseline patient and disease characteristics

Characteristics		N	n (%) or mean ± SD
Age		94	42.5 (15.3)
Gender	Male	94	56 (59.6)
BMI (kg/m2)		91	25.4 (4.5)
Race	American Indian/Alaska Native	94	1 (1.1)
	Asian		5 (5.3)
	White		88 (93.6)
Employment status	Disability		2 (2.1)
	Employed (fulltime, part time < 35 h/week)		63 (67.0)
	Homemaker		3 (3.2)
	Retired		12 (12.8)
	Student		6 (6.4)
	Temporary leave of absence		1 (1.1)
	Unemployed		6 (6.4)
	Unknown		1 (1.1)
Tobacco use	Current smoker	94	2 (2.1)
	Former smoker		34 (36.2)
	Never smoked		55 (58.5)
	Unknown		3 (3.2)
Alcohol use	Non-drinker	94	20 (21.3)
	Ex-drinker		5 (5.3)
	Light (less than 2 drinks per day)		61 (64.9)
	Moderate (2-4 drinks per day)		5 (5.3)
	Unknown		3 (3.2)
Age at UC diagnosis (yr)		98	34.5 (15.3)
Disease duration (yr)		98	7.9 (8.0)
Family history of UC	No	98	59 (60.2)
	Yes		20 (20.4)
	Unknown		19 (19.4)
Montreal classification of extent of UC	E2	97	55 (56.7)
(prior 3 mo)	E3		42 (43.3)
Mayo Endoscopic Subscore	1	90	1 (1.1)
(prior 3 mo)	2		66 (73.3)
	3		23 (25.6)
Endoscopy (prior 6 mo)	Yes	98	91 (92.9)
UC-related ED visit (prior 6 mo)	Yes	98	13 (13.3)
UC-related hospitalization (prior 6 mo)	Yes	98	12 (12.2)
Previous biologic use	Yes	44	5 (11.4)
Medication use:	Corticosteroids	98	63 (64.3)
Since UC diagnosis to prior 6 mo	Imuran (azathioprine)		37 (37.8)
	6-MP		8 (8.2)
	5-ASA		83 (84.7)
	Methotrexate		5 (5.1)
	Cyclosporine		1 (1.0)
Medication use:	Corticosteroids	98	61 (62.2)
Since prior 6 mo to current	Imuran (azathioprine)		39 (39.8)
	6-MP		5 (5.1)
	5-ASA		67 (68.4)
	Methotrexate		8 (8.2)
	Cyclosporine		0 (0.0)

Montreal classification of extent of UC: E2 = left sided (distal) ulcerative colitis, E3 = extensive (pancolitis) ulcerative colitis; Mayo endoscopic subscore: 0 = normal or inactive disease, 1 = mild disease, 2 = moderate disease, 3 = severe disease; 5-ASA: 5-aminosalicylic acid; 6-MP: Mercaptopurine; BMI: Body mass index; ED: Emergency department; UC: Ulcerative colitis.

Table 2 Patient Health Questionnaire–9 items at week 8 and week 52/final visit

Outcome	ITT			Completers
	Baseline (n = 94)	Week 8 (n = 94)	Week 52/final visit (n = 73)	Baseline (n = 48)	Week 8 (n = 48)	Week 52/final visit (n = 47)
PHQ-9 total score
n	94	82	65	48	43	44
mean ± SD	8.8 (6.3)	6.8 (5.3)	6.5 (5.6)	8.2 (6.7)	5.8 (5.6)	4.6 (4.3)
Median	8.0	6.0	5.0	5.0	5.0	3.0
Min, Max	0.0, 26.0	0.0, 26.0	0.0, 22.0	1.0, 26.0	0.0, 26.0	0.0, 15.0
Change from baseline
n		82	65		43	44
mean ± SD		-2.2 (6.1)	-2.4 (7.1)		-2.5 (6.1)	-3.4 (6.8)
P value		0.002	0.008		0.010	0.002
PHQ-9 category, n (%)
Minimal	35 (37.2)	31 (37.8)	28 (43.1)	23 (47.9)	21 (48.8)	25 (56.8)
Mild	23 (24.5)	30 (36.6)	18 (27.7)	8 (16.7)	14 (32.6)	11 (25.0)
Moderate	18 (19.1)	14 (17.1)	11 (16.9)	9 (18.8)	4 (9.3)	7 (15.9)
Moderately severe	11 (11.7)	4 (4.9)	7 (10.8)	4 (8.3)	2 (4.7)	1 (2.3)
Severe	7 (7.4)	3 (3.7)	1 (1.5)	4 (8.3)	2 (4.7)	0 (0.0)
P value		0.280	0.681		0.610	0.542
PHQ-9: Yellow flag category, n (%)
	36 (38.3)	21 (25.6)	19 (29.2)	17 (35.4)	8 (18.6)	8 (18.2)
P value		0.028	0.083		0.021	0.059
PHQ-9: Red flag category, n (%)
Yes	18 (19.1)	7 (8.5)	8 (12.3)	8 (16.7)	4 (9.3)	1 (2.3)
P value		0.013	0.134		0.180	0.034

The yellow flag category was defined as the proportion of patients with a Patient Health Questionnaire–9 total score ≥ 10, and the red flag category was defined as patients with severe depressive symptoms. ITT: Intent-to-treat; Max: Maximum; Min: Minimum; PHQ-9: Patient Health Questionnaire–9 items.

Table 3 Association between clinical response/remission and improvement in Patient Health Questionnaire–9 items total score at week 52/final visit–intent-to-treat and completers populations

Analysis population	Parameter	Model coefficient (SE)	Est. odds ratio (95%CI)	P value
Clinical response
ITT	Baseline PHQ-9 total score	0.17 (0.06)	1.19 (1.05-1.34)	0.005
	Clinical response at week 52: Yes versus No	0.30 (0.65)	1.35 (0.38-4.84)	0.648
	UC duration (years)	0.11 (0.05)	1.11 (1.00-1.24)	0.051
Completers	Baseline PHQ-9 total score	0.20 (0.10)	1.22 (1.00-1.48)	0.049
	Clinical response at week 52: Yes versus No	-1.29 (1.29)	0.28 (0.02-3.43)	0.317
	UC duration (years)	0.14 (0.08)	1.15 (0.98-1.35)	0.079
Clinical remission
ITT	Baseline PHQ-9 total score	0.28 (0.09)	1.33 (1.11-1.59)	0.002
	Clinical remission at week 52: Yes versus No	2.07 (0.88)	7.94 (1.42-44.41)	0.018
	UC duration (years)	0.11 (0.06)	1.11 (1.00-1.24)	0.054
Completers	Baseline PHQ-9 total score	0.22 (0.11)	1.24 (1.00-1.53)	0.045
	Clinical remission at week 52: Yes versus No	1.39 (1.07)	4.00 (0.50-32.37)	0.193
	UC duration (years)	0.14 (0.08)	1.15 (0.98-1.36)	0.095

Clinical response based on simple clinical colitis activity index (SCCAI): decrease from baseline of ≥ 2; Clinical remission: SCCAI ≤ 2; CI: Confidence interval; ITT: Intent-to-treat; PHQ-9: Patient Health Questionnaire–9 Items; SE: Standard error.

Table 4 Change from baseline in other patient-reported outcomes at weeks 8 and 52–intent-to-treat population

PRO measure	Baseline	Change from baseline
	n (%) or mean ± SD	N	Week 8, n (%) or mean ± SD	P value	N	Week 52, n (%) or mean ± SD	P value
EQ-5D-5L	0.78 (0.17)	83	0.05 (0.17)	0.021	65	0.06 (0.24)	0.049
SIBDQ
Total score	4.26 (1.08)	83	0.60 (1.08)	< 0.001	65	0.71 (1.24)	< 0.001
Social function	4.40 (1.91)	82	0.93 (1.78)	< 0.001	64	1.09 (2.11)	< 0.001
Emotional function	4.32 (0.78)	83	0.23 (0.82)	0.013	65	0.20 (0.93)	0.093
Bowel symptoms	4.25 (1.33)	83	0.69 (1.50)	< 0.001	65	0.93 (1.66)	< 0.001
Systemic symptoms	4.11 (1.63)	83	0.63 (1.33)	< 0.001	65	0.68 (1.56)	< 0.001
FACIT-F
Fatigue subscale	30.10 (13.76)	83	3.78 (12.29)	0.006	65	5.41 (13.87)	0.003
Physical fatigue	17.67 (6.59)	83	2.44 (6.27)	< 0.001	65	3.86 (7.11)	< 0.001
Social impact of fatigue	20.69 (5.02)	82	0.52 (3.97)	0.234	65	1.32 (4.60)	0.024
Emotional fatigue	15.37 (4.71)	83	1.10 (4.24)	0.021	65	2.06 (5.26)	0.002
Functional fatigue	15.65 (5.54)	83	2.07 (5.43)	< 0.001	65	2.58 (6.36)	0.002
Trial outcome index	63.42 (24.02)	83	8.29 (21.79)	< 0.001	65	11.85 (24.85)	< 0.001
FACT-G total score	69.38 (16.99)	82	6.16 (15.58)	< 0.001	65	9.82 (18.58)	< 0.001
FACIT-F total score	99.48 (29.04)	82	9.99 (26.34)	< 0.001	65	15.23 (30.64)	< 0.001
MOS Sleep
Sleep problems index I	40.46 (19.16)	83	-4.14 (15.89)	0.020	65	-6.56 (16.21)	0.002
Sleep problems index II	42.30 (19.69)	83	-3.47 (15.66)	0.047	65	-4.92 (16.75)	0.021
Sleep disturbance scale	41.52 (25.58)	83	-3.67 (20.82	0.112	65	-4.22 (22.30)	0.132
Snoring scale	30.22 (33.08)	81	0.00 (24.49)	1.000	63	2.54 (25.78)	0.437
Short of breath scale	11.06 (19.37)	83	2.41 (21.50)	0.310	65	3.08 (19.12)	0.199
Sleep adequacy	42.13 (26.96)	83	8.07 (26.01)	0.006	65	11.69 (26.31)	< 0.001
Somnolence scale	43.12 (27.35)	83	-1.37 (22.42)	0.581	65	-4.00 (25.24)	0.206
Sleep quantity	6.73 (1.41)	82	0.13 (1.29)	0.371	63	0.34 (1.31)	0.042
WPAI1
Work time missed (%)	18.9 (31.1)	48	-6.7 (30.9)		37	-9.4 (35.0)
Work impairment while working (%)	39.5 (28.5)	46	-14.8 (33.1)		38	-14.5 (35.8)
Overall work impairment (%)	44.2 (30.1)	42	-16.2 (30.2)		35	-14.5 (34.4)
Activity impairment (%)	46.0 (31.9)	83	-16.9 (29.8)		64	-16.7 (33.6)
VOLP
Any paid work productivity loss in the past x months (%)	45 (76.3)	58	-5 (-4.6)		47	-17 (-16.7)
Paid work productivity loss in the past x months (hours)	98.5 (122.7)	51	13.5 (127.8)		42	-42.2 (115.7)
Any unpaid work productivity loss in the past 7 d (%)	20 (29.0)	61	-8 (-9.3)		48	-7 (-1.9)
Unpaid work productivity loss in the past 7 d (hours)	3.9 (11.6)	61	-3.4 (12.4)		48	-1.9 (14.8)
Any costs of lost productivity in the past x month (%)	47 (79.7)	58	-5 (-7.3)		47	-15 (-11.6)
Total costs of lost productivity in the past x months ($)	6075.8 (8890.9)	51	-1328 (5594.9)		42	-1998 (7299.7)

¹Due to health.

EQ-5D-5L: EuroQol 5-Dimensions, 5 Levels; CI: Confidence interval; FACIT-F: Functional Assessment Chronic Illness Therapy-Fatigue; MOS: Medical Outcomes Study; PRO: Patient-reported outcome; SIBDQ: Short Quality of Life in Inflammatory Bowel Disease Questionnaire.

Table 5 Overview of adverse events–safety population

	Events (n = 55)	Patients (n = 98)
All AEs	55	18 (18.4%)
Severe AEs	10 (18.2%)	5 (5.1%)
AEs related to study drug	17 (30.9%)	12 (12.2%)
Mild	5 (29.4%)	4 (4.1%)
Moderate	6 (35.3%)	6 (6.1%)
Severe	4 (23.5%)	2 (2.0%)
Not provided	2 (11.8%)	2 (2.0%)
Serious AEs	27 (49.1%)	7 (7.1%)
Number of patients with AEs
Resulting in hospitalization		6 (6.1%)
Resulting in study drug discontinuation		15 (15.3%)
Malignancy in patients ≤ 30 yr	0	0
Death	0	0

Percentages of patients were calculated based on the total number of patients. Percentages of events were based on the total number of events.

AE: Adverse event.