Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis

Table 1 Patient characteristics at baseline

Characteristic	n = 101
Age, years, median (IQR)	35 (28.0, 47.0)
Sex
Male, n (%)	60 (59.4)
Female, n (%)	41 (40.6)
Duration of UC, years, median (IQR)	4.8 (1.5, 10.0)
Disease extent, n (%)
Left-sided colitis	18 (17.8)
Pancolitis	83 (82.2)
Family history of IBD, n (%)	7 (6.9)
Smoking classification, n (%)
Never smoked	66 (65.3)
Current smoker	14 (13.9)
Ex-smoker	21 (20.8)
Comorbidities, n (%)
Hypertension	7 (6.9)
Dyslipidemia	6 (5.9)
Diabetes mellitus	3 (3.0)
Thrombosis	2 (2.0)
Past history of herpes zoster, n (%)	1 (1.0)
Total Mayo score (n = 54), median (IQR)	9.0 (7.0,10.0)
Partial Mayo score, median (IQR)	6.0 (4.0, 7.0)
Mayo endoscopic subscore (n = 54), median (IQR)	2.0 (2.0, 3.0)
1, n (%)	3.0 (5.0, 6.0)
2, n (%)	26 (48.1)
3, n (%)	25 (46.3)
Intractability, n (%)
Steroid dependent	48 (47.5)
Steroid refractory	51 (50.5)
C-reactive protein (mg/dL), median (IQR)	0.3 (0.1, 1.0)
Albumin (g/dL), median (IQR)	3.9 (3.5, 4.2)
White blood cells (/μL), median (IQR)	7180.0 (5490.0, 9160.0)
Lymphocytes (/μL), median (IQR)	1506.0 (1083.0, 1874.0)
Hemoglobin (g/dL), median (IQR)	12.3 (11.1, 13.8)
Total Cholesterol (mg/dL) (n = 71), median (IQR)	179.0 (163.0, 199.0)
Concomitant drugs at baseline, n (%)
5-aminosalicylic acid	68 (67.3)
Systemic corticosteroid	23 (22.8)
Topical corticosteroid	22 (21.8)
History of treatment at baseline
Previous corticosteroid, n (%)	99 (98.0)
Previous immunomodulator, n (%)	70 (69.3)
Previous cytapheresis, n (%)	27 (26.7)
Previous tacrolimus, n (%)	31 (30.7)
Previous biologics, n (%)	67 (66.3)
Anti-TNF-α agent, n (%)	63 (62.4)
Infliximab	38 (37.6)
Adalimumab	27 (26.7)
Golimumab	19 (18.8)
Number of anti-TNF-α agent failure, n (%)
1 agent	44 (43.6)
2 agents	17 (16.8)
3 agents	2 (2.0)
Vedolizumab, n (%)	11 (10.9)
Anti-TNF-α agent and vedolizumab, n (%)	7 (6.9)

IBD: Inflammatory bowel disease; IQR: Interquartile range; TNF-α: Tumor necrosis factor α; UC: Ulcerative colitis.

Table 2 Baseline factors associated with the efficacy of Tofacitinib at week 8

Variable	Univariate analyses			Multivariate analyses
	Non-responder (n = 34)	Responder (n = 67)	P value	Odds ratio	95%CI	P value
Age, years, median (IQR)	32.5 (27.5, 46.0)	37.0 (28.0, 47.5)	0.27	1.02	0.99-1.05	0.28
Sex (M/F), n	20/14	40/27	1.00
Baseline partial Mayo score, median (IQR)	7.0 (5.3, 8.0)	5.0 (4.0, 7.0)	< 0.001	0.61	0.45-0.82	0.001
Disease duration, years, median (IQR)	6.2 (1.7, 9.9)	4.5 (1.6, 10.0)	0.84
Disease extent, n (%)
Left-sided colitis	8 (23.5)	10 (14.9)
Extensive colitis	26 (76.5)	57 (85.1)	0.29
Family history of IBD, n (%)	3 (8.8)	4 (6.0)	0.69
Current smoker, n (%)	5 (14.7)	9 (13.4)	1.00
Intractability (dependent/refractory), n	16/18	32/33	1.00
Albumin, g/dL, median (IQR)	3.9 (3.5, 4.3)	3.9 (3.6, 4.2)	0.88
C-reactive protein, mg/dL, median (IQR)	0.2 (0.1, 0.7)	0.3 (0.1, 1.1)	0.49
White blood cells, /μL, median (IQR)	6660.0 (5107.5, 8415.0)	7260.0 (5760.0, 9460.0)	0.15	1.00	1.00-1.00	0.17
Hemoglobin, g/dL, median (IQR)	12.4 (11.1, 13.7)	12.3 (11.2, 14.0)	1.00
Baseline systemic corticosteroid use, n (%)	8 (23.5)	15 (22.4)	1.00
Previous immunomodulator, n (%)	24 (70.6)	46 (68.7)	1.00
Previous tacrolimus, n (%)	11 (32.4)	20 (29.9)	0.82
Previous biologics, n (%)
Previous anti TNF-α agent	22 (64.7)	41 (61.2)	0.83
Previous vedolizumab	4 (11.8)	7 (10.4)	1.00

CI: Confidence interval; IBD: Inflammatory bowel disease; IQR: Interquartile range; TNF-α: Tumor necrosis factor α.

Table 3 Adverse event, n (%)

Safety profile		Incidence rates per 100 patient-years
Hypercholesterolemia	17 (15.3)	21.1
Herpes zoster	6 (5.4)	7.5
Upper respiratory tract infection	5 (4.5)	6.2
Fever	4 (3.6)	5.0
Headache	3 (2.7)	3.7
Influenza	3 (2.7)	3.7
Lower leg edema	2 (1.8)	2.5
General fatigue	2 (1.8)	2.5
Sore throat	2 (1.8)	2.5
Bronchitis	1 (0.9)	1.2
Herpes labialis	1 (0.9)	1.2
Norovirus enteritis	1 (0.9)	1.2
Clostridioides difficile colitis	1 (0.9)	1.2
Folliculitis	1 (0.9)	1.2
Palpitations	1 (0.9)	1.2
Joint pain	1 (0.9)	1.2
General pain	1 (0.9)	1.2
Dizziness	1 (0.9)	1.2
Sleepiness	1 (0.9)	1.2
Deep vein thrombosis	1 (0.9)	1.2
Dysplasia	1 (0.9)	1.2
Elevation of creatine kinase	1 (0.9)	1.2
Abnormal liver function tests	1 (0.9)	1.2

Table 4 Characteristics of patients who developed herpes zoster

Case	Age	Sex	Prior TNF-α failure	TOF dose (mg/day)	Week of onset	pMS at onset	Lymphocyte count (/μL)	Concomitant drug	Therapy for HZ	TOF therapy	Area of HZ	Postherpetic neuralgia
1	68	F	(+)	10	30	1	1362	5ASA; PPI; ARB	OAD	Continuation	Lower leg	(+)
2	30	F	(+)	20	5	0	1570	Prednisolone 10 mg	OAD	Resumption after drug withdrawal	Head; Neck; Back	(-)
3	25	F	(+)	10	23	1	1102	5ASA	OAD	Continuation	Back	(-)
4	48	M	(+)	10	31	1	1810	5ASA	OAD	Resumption after drug withdrawal	Abdomen	(-)
5	54	F	(-)	20	5	1	2127	Iron preparations	OAD	Discontinuation	Buttocks	(-)
6	53	M	(+)	10	26	0	922	(-)	OAD	Continuation	Back	(-)

5ASA: 5-aminosalicylate; ARB: Angiotensin II receptor blocker; HZ: Herpes zoster; OAD: Oral antiviral drug; pMS: Partial Mayo Score; PPI: Proton pump inhibitor; TNF-α: Tumor necrosis factor α; TOF: Tofacitinib.