Performance of tacrolimus in hospitalized patients with steroid-refractory acute severe ulcerative colitis

Table 1 Demographic and disease-specific baseline characteristics of the 22 included patients

Characteristic	n = 22
Gender, n (m/f)	9/13
Age at admission (yr, mean ± SEM)	33.2 ± 7.1 (range: 18-66)
Age at first diagnosis (yr, mean ± SEM)	25.5 ± 5.6 (n = 21, uk in 1) (range: 14-58)
Disease duration at admission (yr, mean ± SEM )	6.2 ± 1.3 (n = 21, uk in 1) (range: 0-19)
Disease extent according to Montreal classification at admission, n (E2:E3)	4:18
Previous anti-TNFα therapy failure, n (%)	5/22 (22.7)
Previous thiopurine therapy, n (%)	9/22 (40.9)
Systemic steroid therapy at admission, n (%)	15/22 (68.2)
Oral mesalamine at admission, n (%)	15/22 (68.2)
Anti-TNFα therapy at admission, n (%)	1/22 (4.5) (third infliximab infusion had been applied 23 d prior to admission)
Thiopurine therapy at admission, n (%)	1/22 (4.5) (on azathioprine for 32 mo prior to admission)
Body mass index (BMI) at admission (kg/m2, mean ± SEM)	20.3 ± 4.3 (range: 12.1-26.8)
Body temperature at admission (°C, mean ± SEM)	38.0 ± 0.2 (range: 36.6-39.6)
Heart rate at admission (beats per minute, mean ± SEM)	97.2 ± 2.9 (range: 80-135)
Number of bowel movements per 24 h at admission (mean ± SEM)	13.5 ± 1.4 (range: 7-30)
Presence of bloody stools at admission, n (%)	22/22 (100)
Plasma CRP concentration at hospital admission (mg/L, mean ± SEM)	87.5 ± 14.3 (range: 2.0-310.4)
WBC count at admission (/nL, mean ± SEM)	12.6 ± 1.0 (range: 4.4-22.8)
Platelet count at admission (/nL, mean ± SEM)	453 ± 29 (232-724)
Blood hemoglobin concentration at admission (g/dL, mean ± SEM)	10.8 ± 0.3 (7.7-14.5)
Endoscopic Mayo score at admission, n (Mayo 2:Mayo 3) (sigmoidoscopy)	7:15

n: Number; m: Male; f: Female; SEM: Standard error of the mean; TNF: Tumor necrosis factor; CRP: C-reactive protein; uk: Unknown; WBC: White blood cell.

Table 2 Clinical data obtained during the hospital stay

Variable	n = 22
Systemic antibiotic treatment during hospital stay, n (%)	21/22 (95.5)
Duration of IV steroid therapy prior to start of tacrolimus therapy (mean ± SEM)	6.7 ± 0.7
Use of parenteral nutrition during hospital stay, n (%)	9/22 (40.9)
Blood transfusion during hospital stay, n (%)	10/22 (45.5)
Oral mesalamine therapy during hospital stay, n (%)	17/22 (77.3)
Stay in intermediate care unit during part of the hospitalization, n (%)	4/22 (18.2)
Duration of hospital stay, d (mean ± SEM)	22.8 ± 4.9
Addition of a second immunosuppressive as a maintenance therapy during hospital stay, n (%)	10/22 (45.5)
Anti-integrin (vedolizumab)	5/22 (22.7)
Thiopurine (azathioprine or 6-mercaptopurine)	5/22 (22.7)

SEM: Standard error of the mean; IV: Intravenous.

Table 3 Characteristics and outcome of tacrolimus therapy

Variable	n = 22
Intravenous initiation of tacrolimus treatment, n (%)	15/22 (68.2)
Duration of intravenous tacrolimus therapy (d, mean ± SEM)	4.0 ± 0.9 (range: 2-13)
Duration of tacrolimus therapy until discharge from the hospital or transfer to surgery (d, mean ± SEM)	15.9 ± 3.4 (n = 20)
Initial dose of intravenous tacrolimus (mg/24 h, mean ± SEM)	1.4 ± 0.4 (n = 15)
Initial dose of intravenous tacrolimus per body weight (μg/kg/24 h, mean ± SEM)	26 ± 3 (n = 15)
Initial dose of oral tacrolimus (mg/24 h, mean ± SEM)	5.3 ± 2.2 (n = 7)
Initial dose of oral tacrolimus per body weight (μg/kg/24 h, mean ± SEM)	95 ± 31 (n = 7)
Time to achievement of target tacrolimus trough level after intravenous treatment initiation (d, mean ± SEM)	3.1 ± 0.4 (n = 14)
Time to achievement of target tacrolimus trough level after oral treatment initiation (d, mean ± SEM)	4.2 ± 1.2 (n = 7)
Total duration of tacrolimus therapy to end of therapy or last follow-up (d, mean ± SEM)	128 ± 28.5 (range: 2-266)
Patients discharged from the hospital under continued tacrolimus therapy, n (%)	19/22 (86.4)
Clinical response to tacrolimus therapy, including remission, n (%)	18/22 (81.8)
Clinical remission under tacrolimus therapy, n (%)	8/22 (36.4)
Colectomy during follow-up, n (%)	7/22 (31.8)
Direct transmission to the surgery department after primary failure of tacrolimus therapy, n (%)	2/22 (9.1)
Time from start of tacrolimus therapy to colectomy (d, mean ± SEM)	97.4 ± 20.8 (range: 5-194)

SEM: Standard error of the mean.

Table 4 Documented suspected side effects of tacrolimus during intravenous and oral treatment

Suspected side effect	n = 22
None, n (%)	10/22 (45.5)
Treatment discontinuation due to side effects, n (%)	2/22 (9.1) (1 due to severe vomiting, 1 due to anemia and leukopenia)
Nausea ± vomiting, n (%)	3/22 (13.6)
Stomach pain, n (%)	1/22 (4.5)
Headache, n (%)	1/22 (4.5)
Tremor, n (%)	4/22 (18.2)
Paresthesias, n (%)	1/22 (4.5)
Photosensitivity, n (%)	1/22 (4.5)
Itching rash, n (%)	1/22 (4.5)
Joint or back pain, n (%)	1/22 (4.5)
Muscle pain or cramps, n (%)	2/22 (9.1)
Temperature intolerance, n (%)	3/22 (13.6)
Anemia, leukopenia, n (%)	1/22 (4.5)
Loss of hair, n (%)	1/22 (4.5)