Table 1 Characteristics of included studies

Brian G Feagan 2023 [17]

Canada

2

FM6-12; EMS ≥ 2

aminosalicylates and corticosteroids (prednisone

or equivalent)

Guselkumab

(week 0, 4, 8 200 mg)

Golimumab

(0 week 200 mg, 100 mg at week2, then 100 mg every 4 week)

12

weeks

39.1(13.67)

38.1(10.47)

40/71

42/72

69.6(16.72)

73.9(17.11)

5.4(5.70)

4.7(4.48)

Wan XM 2022 [18]

China

Not reported

Not reported

-

Adamumab

(0week160mg, 80 mg at week 2,then 40 mg/week)

Mesalazine

12 weeks

42. 24 (13. 46)

43. 32 (13. 21)

15/28

14/28

-

-

3.63 (2. 23)

3. 32 (2. 32)

Severine Vermeire 2022 [19]

Canada

3

FMS6-12;CRES ≥ 2; RBS ≥ 1; SFS ≥ 1

5-aminosalicylates, Oral corticosteroids, Immuno­­suppressants such as AZA, 6-mercaptopurine, and metho­trexate

Etrolizumab

(105 mg once every 4 weeks)

Placebo

10 weeks

36 (18–77)*

38 (18–69)*

60/108

52/106

BMI:24 (13–80)*

BMI:25 (15–46)*

5.4 (0.6–44.0)*

5.9 (0.3–40.4)*

David T Rubin 2022 [20]

USA

3

FMS6-12; EMS ≥ 2; RBS ≥ 1

oral 5-aminosalicylates,Oral corticosteroids, Immuno–suppressants such as AZA, 6-mercaptopurine, and metho­trexate

Etrolizumab

(105 mg once every 4 weeks)

Adalimumab

(160 mg on day 1, 80 mg at week 2;40 mg at weeks 4, 6, and 8)

Placebo

8 weeks

36.5 (18–79)*

41.0 (19–75)*

36.0 (19–78)*

74/144

82/142

39/72

BMI:22.7 (15.0–33.6)*

BMI:24.3 (15.7–43.3)*

BMI:23.2 (15.6–40.6)*

3.4 (0.4–41.9)*

4.0(0.3–36.4)*

4.7 (0.3–40.8)*

Etrolizumab

(105 mg once every 4 weeks)

Adalimumab

(160 mg on day 1, 80 mg at week 2;40 mg at weeks 4, 6, and 8)

Placebo

8 weeks

39.0 (18–77)*

38.0 (18–71)*

36.5 (18–79)*

84/143

81/143

38/72

BMI:25.0 (16.4–48.9)*

BMI:24.1 (16.4–40.7)*

BMI:23.7 (16.9–45.8)*

3.6 (0.3–58.8)*

4.1 (0.3–37.9)*

4.0 (0.3–25.4)*

Laurent Peyrin-Biroulet 2022 [21]

France

3

FMS6-12; EMS ≥ 2; RBS ≥ 1

oral 5-aminosalicylates, Oral corticosteroids, Immunosuppressants such as AZA, 6-mercaptopurine, and methotrexate

Etrolizumab

(105 mg once every 4 weeks)

Placebo

14 weeks

39.0 (18–76)*

36.0 (18–76)*

224/384

54/95

BMI:24.3 (14.3–62.1)*

BMI:24.4 (15.5–46∙2)*

7.10 (0.6–44.0)*

7.36 (0.8–40.9)*

Masakazu Nagahori 2021 [22]

Japan

3

FMS6-12; EMS ≥ 2

Not reported

Vedolizumab

(300 mg at Weeks 0, 2, and 6)

Placebo

6 weeks

42.3(14.4)

44.0(16.0)

99/164

55/82

-

-

7.2 (6.2)

8.6 (8.0)

Taku Kobayashi 2021 [23]

Japan

3

FM6-12; EMS ≥ 2

Oral corticosteroids or AZA or 6-mercaptopurine

Vedolizumab

(108 mg Q2W)

Vedolizumab

(300 mg Q8W)

Placebo

44 weeks

46.0(15.5)

54.5(19.1)

43.6(13.0)

7/10

2/2

6/10

62.9(16.3)

61.8(6.8)

58.2(10.6)

8.2(8.0)

7.1(4.0)

10.3(6.6)

William J. Sandborn 2020 [24]

USA

3

FM6-12; EMS ≥ 2

Mesalamine, AZA, 6-mercaptopurine, oral corticosteroids

Vedolizumab

(108 mg Q2W SC)

Vedolizumab

(300 mg Q8W IV)

Placebo

48 weeks

38.1 (13.1)

41.6 (14.1)

39.4 (11.7)

65/106

31/54

34/56

71.6 (17.2)

77.0 (16.9)

74.0 (20.9)

8.2 (5.9)

8.0 (6.2)

7.4 (7.1)

Remo Panaccione 2020 [25]

Canada

2A

FM6-12; EMS ≥ 2

aminosalicylic,

Immunosuppressants,

oral corticosteroids

Ustekinumab

(90 mg Q12w)

Ustekinumab

(90 mg Q8w)

Placebo

44 weeks

40.4 (13.22)

39.9 (12.92)

42.9 (14.54)

77/141

82/143

73/115

71.60 (60.00;

83.80)

70.80 (59.00;

85.30)

72.00 (60.00;

79.40)

-

-

Raja Atreya 2020 [26]

Germany

2B

FM6-12; EMS ≥ 2

5-aminosalicylic acid or sulphasalazine or glucocorticosteroids

Cobitolimod

(2 *31 mg)

Cobitolimod

(2 *125 mg)

Cobitolimod

(4 *125 mg)

Cobitolimod

(2 *250 mg)

Placebo

3 weeks

47.4 (16.4)

47.0 (16.9)

47.2 (14.9)

46.2 (14.0)

45.5 (15.2)

26/40

20/43

23/42

36/42

33/44

75.5 (16.7)

71.5 (14.9)

73.1 (17.5)

73.3 (13.2)

78∙1 (12.9)

7∙9 (6.5)

8∙5 (7.4)

8∙1 (6.8)

7∙9 (6.8)

7∙4 (7.3)

B.E. Sands 2019 [27]

USA

Not report

FM6-12; EMS ≥ 2

Aminosalicylates, corticosteroids, immunomodulators

Ustekinumab

(6 mg/kg)

Ustekinumab

(130 mg)

Placebo

8 weeks

41.7(13.7)

42.2(13.9)

41.2(13.5)

195/320

190/322

197/319

73.0(19.3)

73.7(16.8)

72.9(16.8)

8.2(7.8)

8.1(7.2)

8.0(7.2)

Chen BL 2017 [28]

China

Not report

FMS6-12

Mercaptopurine

AZA; Mesalazine

Methylprednisolone

Infliximab

(5 mg/kg at week 0,2,6,14,22)

Placebo

26 weeks

39.2(12.6)

37.0(11.4)

21/50

29/49

60.69(13.62)

57.16(11.63)

5.21(5.11)

5.91(5.05)

Séverine Vermeire 2017 [29]

USA

2

FMS ≥ 6; EMS ≥ 2

Not reported

PF-00547659

(7.5 mg Q4W)

PF-00547659

(22.5 mg Q4W)

PF-00547659

(75 mg Q4W)

PF-00547659

(225 mg Q4W)

Placebo

12 weeks

41.3 (12.5)

42.1 (14.7)

37.7 (12.4)

41.3 (13.2)

38.6 (12.7)

39/71

45/70

38/73

42/70

44/73

BMI:24.3 (4.2)

BMI:24.3 (4.5)

BMI:25.4 (6.0)

BMI:25.4 (5.8)

BMI:25.5 (6.0)

-

-

William J. Sandborn 2016 [30]

USA

2b

FMS6-12; EMS ≥ 2

Aminosalicylates, Prednisone or AZA, or 6-mercaptopurine

Eldelumab

(day1-8, every other week thereafter)

Eldelumab

(day1-8, every other week thereafter)

Placebo

64 days

40.8 (15.1)

39.0 (12.7)

42.7 (14.2)

54/84

44/85

43/83

-

-

3.9 (0.5–39.6)*

5.0 (0.5–27.0)*

5.7 (0.5–31.2)*

P. Rutgeerts 2015 [31]

Belgium

2/3

FMS6-12; EMS ≥ 2

Not reported

golimumab

(1 mg/kg)

golimumab

(2 mg/kg)

golimumab

(4 mg/kg)

Placebo

6 weeks

40.7(15.51)

42.3(13.14)

39.9(14.07)

40.9(12.58)

41/62

36/75

50/77

47/77

-

-

6.2(5.07)

7.6(8.04)

6.5(6.54)

6.8(6.59)

Yasuo Suzuki 2014 [32]

Japan

2/3

FMS6-12; EMS ≥ 2

Prednisolone, AZA, 6-mercaptopurine

Adalimumab

(80 mg at week 0, then 40 mg every other week)

Adalimumab

(160/80 mg at weeks 0/2, then 40 mg every other week)

Placebo

52 weeks

44.4(15.0)

42.5(14.6)

41.3(13.6)

50/87

61/90

70/96

58.7(11.1)

60.1(12.3)

60.8(14.1)

8.3 (7.7)

7.8 (7.1)

7.8 (6.6)

William J. Sandborn 2014 [33]

USA

2/3

FMS6-12; EMS ≥ 2

Aminosalicylate

corticosteroids

Golimumab

(200 mg and then 100 mg)

Golimumab

(400 mg and then 200 mg)

Placebo

6 weeks

40.0(3.54)

40.7(13.75)

39.0(13.04)

180/331

201/331

175/331

-

-

6.4(6.17)

6.4(6.27)

6.0(6.65)

Remo Panaccione 2014 [34]

UK

Not reported

FMS6-12;

none

Infliximab

(5 mg/kg at weeks 0,2,6)

Azathioprine

(2.5 mg/kg)

Infliximab + Azathioprine

16 weeks

38.5 (12.7)

40.7 (13.2)

38.0 (12.2)

42/78

33/79

48/80

-

-

6.3 (6.5)

6.6 (7.8)

5.2 (5.1)

Lloyd Mayer 2014 [35]

USA

2

FMS6-12; EMS ≥ 2

5-Aminosalicylates, prednisolone ≤ 20 mg/day,6-mercaptopurine

BMS-936557

(10 mg/kg every other week)

Placebo

8 weeks

44.7 (12.8)

41.8 (14.2)

37/55

31/54

81.9 (16.1)

74.5 (18.1)

6.7 (7.8)

5.5 (4.4)

William J. Sandborn 2014 [36]

USA

2/3

FMS6-12; EMS ≥ 2

Aminosalicylates,

Corticosteroids,

mesalamine

Golimumab

(50 mg Q4W)

Golimumab

(100 mg Q4W)

Placebo

54 weeks

41.4(13.84)

39.1(13.11)

40.2 ± 14.0

77/154

89/154

75/156

-

-

6.8(6.93)

7.2(7.04)

6.9(6.96)

William J. Sandborn 2014 [37]

USA

Not reported

FMS ≥ 10; SFS ≥ 2

mesalamine, AZA, 6-mercaptopurine, or methotrexate

Visilizumab

(5 mg/kg on days 1 and 2)

Placebo

45 days

40.4 (12.9)

40.8 (13.5)

52/84

28/43

75.5 (17.3)

74.8 (16.8)

6.4 (6.8)

6.8 (7.1)

BRUCE E. SANDS 2012 [38]

USA

2

FMS6-12;

Prednisone, AZA, mercaptopurine, 5-aminosalicylate

Basiliximab

(20 mg, at week0,2,4)

Basiliximab

(40 mg, at week0,2,4)

Placebo

8 weeks

43 (14)

39 (12)

38 (11)

27/46

31/52

31/51

70.3 (15)

70.3 (19)

69.7 (18)

-

-

William J. Sandborn 2012 [39]

USA

3

FMS6-12; EMS ≥ 2

Prednisone, AZA, 6-mercaptopurine, 5-aminosalicylate

Adalimumab

(160 mg at week 0, 80 mg at week 2, then 40 mg every other week)

Placebo

52 weeks

39.6(12.47)

41.3 ± 13.22

142/248

152/246

75.3(17.71)

77.1(17.31)

8.1(7.09)

8.5(7.37)

G Van Assche 2006 [40]

Japan

Not reported

FMS5-10;

Oral corticosteroid

5-aminosalicylates, methylprednisolone 32 mg/day or less (or equivalent dose of other corticosteroid), AZA, and 6-mercaptopurine were permitted

Daclizumab

(1 mg/kg, at weeks 0 and 4)

Daclizumab

(2 mg/kg,at weeks 0, 2, 4, and 6)

Placebo

6 weeks

47.4 (14.09)

42.6 (15.37)

40.7 (13.23)

29/56

25/47

33/56

76.6 (19.45)

79.8 (19.29)

80.5 (19.24)

7.8 (6.62)

8.3 (8.06)

6.8 (7.35)

Paul Rutgeerts 2005 [41]

Belgium

Not reported

FMS6-12;

corticosteroids alone or in combination with AZA or mercaptopurine

Infliximab

(5 mg/ kilogram Q8w)

Infliximab

(10 mg/ kilogram Q8w)

Placebo

54 weeks

42.4(14.3)

41.8(14.9)

41.4(13.7)

78/121

72/122

72/121

80.0(17.8)

76.9(17.1)

76.8(16.2)

5.9(5.4)

8.4(8.1)

6.2(5.9)

corticosteroids alone or in combination with AZA or mercaptopurine and medications containing 5-aminosalicylates

Infliximab

(5 mg/ kilogram Q8w)

Infliximab

(10 mg/ kilogram Q8w)

Placebo

30 weeks

40.5(13.1)

40.3(13.3)

39.9(13.5)

76/121

68/120

71/123

78.4(17.8)

79.6(20.6)

76.1(17.4)

6.7(5.3)

6.5(5.8)

6.5(6.7)

C S J Probert 2003 [42]

UK

Not reported

ulcerative colitis symptom score of 6 or more

Prednisolone 30 mg

Infliximab

(5 mg/ kilogram at weeks 0, 2)

Placebo

2 weeks

41 (35.5–50.5)*

40 (29–43.5)*

-

-

66 (61–78)*

72 (60–8)*

-

-