Clinical outcomes of upadacitinib dose escalation in inflammatory bowel disease: A single-center retrospective cohort study

Table 1 Baseline characteristics of the study population, n (%)/mean ± SD/median (interquartile range)

Characteristic	Value
Age (years)	34 (26-46)
Female sex	24 (43)
Race/ethnicity
White	42 (75)
Black	8 (14)
Asian	3 (5)
Other	3 (5)
IBD subtype
Crohn’s disease	38 (68)
Ulcerative colitis	18 (32)
Prior biologic exposure	2.49 ± 1.25

IBD: Inflammatory bowel disease.

Table 2 Indications for off-label escalated dosing of upadacitinib

Reason for off-label escalated dosing	Number of patients
Symptoms	22
Endoscopic activity	19
Laboratory findings	3
Symptoms and endoscopic activity	5
Symptoms and laboratory findings	3
Endoscopic activity and laboratory findings	2
Symptoms, endoscopic activity, and laboratory findings	1
Imaging and laboratory findings	1

Categories represent mutually exclusive indications (n = 56 total patients); each patient is counted once based on the combination of clinical symptoms, endoscopic activity, imaging findings, and laboratory abnormalities prompting dose escalation.

Table 3 Symptom improvement in entire cohort, n (%)

Symptom	Before, n = 49	After, n = 49	P value
Any symptoms	44 (89.8)	35 (71.4)	0.022
Abdominal pain	28 (57.1)	14 (28.6)	0.003
Urgency	22 (45.0)	8 (16.3)	0.003
Hematochezia	24 (49.0)	10 (20.4)	0.004
Diarrhea	27 (55.1)	18 (36.7)	0.049
Extra-intestinal manifestations	20 (35.7)	13 (23.2)	0.089
Constipation	5 (10.2)	2 (4.1)	0.375
Mucus	7 (14.3)	4 (8.2)	0.450
Nausea	8 (16.3)	7 (14.3)	1.000
Vomiting	2 (4.1)	1 (2.0)	1.000
Tenesmus	5 (10.2)	4 (8.2)	1.000

Gastrointestinal and extra-intestinal symptoms were assessed in all patients. P values were calculated using McNemar’s test. Seven patients were excluded due to lack of paired data.

Table 4 Symptom improvement in patients escalated for uncontrolled symptoms, n (%)

Symptom	Before, n = 30	After, n = 30	P value
Any symptoms	30 (100)	25 (83.3)	0.063
Abdominal pain	19 (63.3)	8 (26.7)	0.003
Urgency	15 (50.0)	7 (23.3)	0.077
Hematochezia	16 (53.3)	5 (16.7)	0.007
Diarrhea	19 (63.3)	12 (40.0)	0.039
Extra-intestinal manifestations	14 (46.7)	10 (33.3)	0.160
Mucus	4 (13.3)	2 (6.7)	0.625
Tenesmus	1 (3.3)	3 (10.0)	0.625
Constipation	3 (10.0)	2 (6.7)	1.000
Nausea	5 (16.7)	5 (16.7)	1.000
Vomiting	2 (6.7)	1 (3.3)	1.000

Gastrointestinal and extra-intestinal symptoms were documented among patients escalated for uncontrolled symptoms. P values were calculated using McNemar’s test.

Table 5 Biomarker outcomes before and after dose escalation (paired observations), median (interquartile range)

Outcome	Before	After	P value
CRP (mg/L)	0.25 (0-1.75)	0 (0-0.96)	0.470
ESR (mm/hour)	27 (7.25-43.25)	17.5 (7.75-59.5)	0.630
Fecal calprotectin (μg/g)	276 (136.5-1030.5)	146 (46-497.5)	0.390

P values were calculated using the Wilcoxon signed-rank test (two-sided). Paired data were available for C-reactive protein (n = 40), erythrocyte sedimentation rate (n = 12), and fecal calprotectin (n = 21). CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate.

Table 6 Endoscopic outcomes before and after dose escalation (paired observations), median (interquartile range)

Endoscopic outcome	Before	After	P value
Mayo endoscopic subscore	3 (2-5)	0 (0-0.5)	0.250
SES-CD	7 (5.5-9)	7 (4-9.5)	0.440

Mayo endoscopic subscore (ulcerative colitis); n = 3 paired observations. Simple endoscopic score for Crohn’s disease; n = 7 paired observations (6 non-zero paired differences included in Wilcoxon analysis). Values are presented as median (interquartile range). P values were calculated using the two-sided Wilcoxon signed-rank test. Given the small sample sizes, results should be interpreted with caution. SES-CD: Simple endoscopic score for Crohn’s disease.