Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website https://www.gastrores.org

Original Article

Volume 16, Number 6, December 2023, pages 289-306

Comparing the Efficacy and Safety of Adalimumab and Vedolizumab in Treating Moderate to Severe Crohn’s Disease and Ulcerative Colitis

Figure 2. Forest plot for achieving clinical remission at induction phase in (a) ADA and (b) VDZ versus control group among CD patients. ADA: adalimumab; CD: Crohn’s disease; VDZ: vedolizumab.

Figure 3. Forest plot for achieving clinical response at induction phase in (a) ADA and (b) VDZ versus control group among CD patients. ADA: adalimumab; CD: Crohn’s disease; VDZ: vedolizumab.

Figure 4. Forest plot for achieving clinical remission at maintenance phase in (a) ADA and (b) VDZ versus control group among CD patients. ADA: adalimumab; CD: Crohn’s disease; VDZ: vedolizumab.

Figure 5. Forest plot for achieving clinical response at maintenance phase in (a) ADA and (b) VDZ versus control group among CD patients. ADA: adalimumab; CD: Crohn’s disease; VDZ: vedolizumab.

Figure 6. Forest plot for achieving clinical remission at induction phase in (a) ADA and (b) VDZ versus control group among UC patients. ADA: adalimumab; UC: ulcerative colitis; VDZ: vedolizumab.

Figure 7. Forest plot for achieving clinical response at induction phase in (a) ADA and (b) VDZ versus control group among UC patients. ADA: adalimumab; UC: ulcerative colitis; VDZ: vedolizumab.

Figure 8. Forest plot for achieving mucosal healing at induction phase in (a) ADA and (b) VDZ versus control group among UC patients. ADA: adalimumab; UC: ulcerative colitis; VDZ: vedolizumab.

Figure 9. Forest plot for achieving clinical remission at maintenance phase in (a) ADA and (b) VDZ versus control group among UC patients. ADA: adalimumab; UC: ulcerative colitis; VDZ: vedolizumab.

Figure 10. Forest plot for achieving clinical response at maintenance phase in (a) ADA and (b) VDZ versus control group among UC patients. ADA: adalimumab; UC: ulcerative colitis; VDZ: vedolizumab.

Figure 11. Forest plot for achieving mucosal healing at maintenance phase in (a) ADA and (b) VDZ versus control group among UC patients. ADA: adalimumab; UC: ulcerative colitis; VDZ: vedolizumab.

Figure 12. Forest plot for serious adverse events in (a) ADA and (b) VDZ versus control group among CD patients. ADA: adalimumab; CD: Crohn’s disease; VDZ: vedolizumab.

Figure 13. Forest plot for serious adverse events in (a) ADA and (b) VDZ versus control group among UC patients. ADA: adalimumab; UC: ulcerative colitis; VDZ: vedolizumab.

**Table 1.** Characteristics of Included Studies
Study	Location	Period	Design	Study phase	Name of trial	Sample size	Mean age, years	Male sex, %	Trial duration, weeks	Outcomes
Chen et al, 2020 [12]	15 sites in China	August 17, 2015 to December 15, 2017	Multicenter, phase III randomized trial (The study comprised an 8-week double-blind (DB) period followed by an 18-week open-label (OL) period)	Induction	-	205	32.9	68%	26	-Clinical remission at week 4. -Clinical response at week 4. -Adverse events
Colombel et al, 2007 [13]	92 sites in Europe, the United States, and Canada	July 2003 to September 2005	Multicenter, phase 3, randomized, double-blind, placebo-controlled trial	Maintenance	Crohn’s Trial of the Fully Human Antibody Adalimumab for Remission Maintenance (CHARM)	854	37.1	11.9%	56	-Clinical response at weeks 26 and 56. -Clinical remission at weeks 26 and 56. -Adverse events
Hanauer et al, 2006 [14]	55 centers in Europe, the United States, and Canada	July 24, 2002 to December 18, 2003	Multicenter, randomized, double-blind, placebo-controlled trial	Induction	Clinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn’s Disease (CLASSIC-I)	299	38	46%	4	-Clinical remission at week 4. -Clinical response at week 4. -Adverse events
Rutgeerts et al, 2012 [15]	19 sites in Europe, the United States, and Canada	August 2006 to September 2008	Randomized, double-blind, placebo-controlled, maintenance/withdrawal study of adalimumab	Induction and Maintenance	Extend the safety and efficacy of adalimumab through endoscopic healing (EXTEND)	129	37.1	37.2%	52	-Clinical remission at weeks 12 and 52. -Clinical response at weeks 12 and 52. -Mucosal healing at weeks 12 and 52. -Adverse events.
Sandborn et al, 2007a [16]	52 sites in the United States, Canada, and Europe	November 2004 to December 2005	Randomized, double-blind, placebo-controlled trial	Induction	-	325	38	35%	4	-Clinical remission at week 4. -Clinical response at week 4. -Adverse events.
Sandborn et al, 2007b [17]	Multi-countries	August 28, 2002 to January 12, 2005	Multi-center, randomized, double-blind, placebo-controlled trial	Maintenance	Clinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn’s Disease (CLASSIC-II)	55	36	40%	56	-Clinical remission at week 56. -Clinical response at week 56. -Adverse events.
Watanabe et al, 2012 [18]	Japan	January 2007 to December 2008	Multicenter, randomized, double-blind, placebo-controlled trial	Induction and maintenance	-	90	31.1	59.9%	56	-Clinical remission at week 4 and 56. -Clinical response at week 4 and 56. -Adverse events.
Sandborn et al, 2013 [19]	285 medical centers in 39 countries	December 2008 to May 2012	Phase 3, randomized, parallel-group, double-blind, placebo-controlled study	Induction and maintenance	GEMINI 2	1115	36.1	46.6%	52	-Clinical remission at week 6 and 52. -Clinical response at week 6 and 52. -Adverse events.
Sands et al, 2014 [20]	107 sites in North America, Europe, Asia, Africa, and Australia	November 2010 to April 2012	Phase 3, randomized, placebo-controlled, double-blind, multinational, multicenter trial	Induction	GEMINI 3	315	35.8	56.5%	10	-Clinical remission at week 6 and 10. -Clinical response at week 6 and 10. -Adverse events.
Vermeire et al, 2022 [21]	169 sites in 30 countries	December 2015 to May 2019	Randomized, double-blind, placebo-controlled, phase 3 trial	Maintenance	VISIBLE 2	409	37	53.2%	52	-Clinical remission at week 52. -Clinical response at week 52. -Adverse events.
Watanabe et al, 2020 [22]	77 centers in Japan	January 28, 2014 to November 16, 2017	A prospective, multicenter, randomized, double-blind, placebo-controlled phase 3 trial	Induction and maintenance	-	157	34.6	64%	60	-Clinical remission at weeks 10 and 60. -Clinical response at weeks 10 and 60. -Adverse events.
Croft et al, 2021 [23]	24 hospitals in 10 countries	January 1, 2014 to December 22, 2020	A double-blind, placebo-controlled phase 3 trial	Induction and maintenance	ENVISION I	93	14.1	45%	52	-Clinical remission at weeks 8 and 52. -Clinical response at week 52. -Mucosal healing at week 52. -Adverse events.
Reinisch et al, 2011 [24]	94 centers in North America and Europe	August 2007 to February 2010	Phase III, multicenter, randomized, double-blind, placebo-controlled trial	Induction	-	390	37.5	62.3%	8	-Clinical remission at week 8. -Clinical response at week 8. -Mucosal healing at week 8. -Adverse events.
Sandborn et al, 2012 [25]	103 centers in North America, Europe, Australia, New Zealand, and Israel	November 2006 and March 2010	Phase 3, multicenter, randomized, double-blind, placebo-controlled trial	Induction and maintenance	-	494	40.4	59.5%	52	-Clinical remission at weeks 8 and 52. -Clinical response at weeks 8 and 52. -Mucosal healing at weeks 8 and 52. -Adverse events.
Suzuki et al, 2014 [26]	Japan	February 2009 to May 2011	Phase II/III, randomized, double-blind, placebo-controlled study	Induction and maintenance	-	273	42.7	62.7%	52	-Clinical remission at weeks 8 and 52. -Clinical response at weeks 8 and 52. -Mucosal healing at weeks 8 and 52. -Adverse events.
Feagan et al, 2013 [27]	211 medical centers in 34 countries from 2008 to 2012	2008 to 2012	Phase 3, randomized, double-blind, placebo-controlled study	Induction and maintenance	-	895	40.3	58.7%	52	-Clinical remission at weeks 6 and 52. -Clinical response at week 6. -Mucosal healing at weeks 6 and 52. -Adverse events.
Motoya et al, 2019 [28]	86 sites in Japan	February 2014 to November 2015	Phase 3, randomized, double-blind, placebo-controlled study	Induction and maintenance	-	292	42.9	61.3%	60	-Clinical remission at weeks 10 and 60. -Clinical response at weeks 10 and 60. -Mucosal healing at weeks 10 and 60.
Sandborn et al, 2020 [29]	141 sites in 29 countries	December 18, 2015 to August 21, 2018	Phase 3, randomized, placebo-controlled, double-blind, double-dummy trial	Maintenance	VISIBLE 1	216	39.7	59.8%	52	-Clinical response at week 52. -Clinical remission at week 52. -Mucosal healing at week 52. -Adverse events.

Table 1. Characteristics of Included Studies

Study

Location

Period

Design

Study phase

Name of trial

Sample size

Mean age, years

Male sex, %

Trial duration, weeks

Outcomes

Chen et al, 2020 [12]

15 sites in China

August 17, 2015 to December 15, 2017

Multicenter, phase III randomized trial (The study comprised an 8-week double-blind (DB) period followed by an 18-week open-label (OL) period)

Induction

205

32.9

68%

-Clinical remission at week 4. -Clinical response at week 4. -Adverse events

Colombel et al, 2007 [13]

92 sites in Europe, the United States, and Canada

July 2003 to September 2005

Multicenter, phase 3, randomized, double-blind, placebo-controlled trial

Maintenance

Crohn’s Trial of the Fully Human Antibody Adalimumab for Remission Maintenance (CHARM)

854

37.1

11.9%

-Clinical response at weeks 26 and 56. -Clinical remission at weeks 26 and 56. -Adverse events

Hanauer et al, 2006 [14]

55 centers in Europe, the United States, and Canada

July 24, 2002 to December 18, 2003

Multicenter, randomized, double-blind, placebo-controlled trial

Induction

Clinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn’s Disease (CLASSIC-I)

299

46%

-Clinical remission at week 4. -Clinical response at week 4. -Adverse events

Rutgeerts et al, 2012 [15]

19 sites in Europe, the United States, and Canada

August 2006 to September 2008

Randomized, double-blind, placebo-controlled, maintenance/withdrawal study of adalimumab

Induction and Maintenance

Extend the safety and efficacy of adalimumab through endoscopic healing (EXTEND)

129

37.1

37.2%

-Clinical remission at weeks 12 and 52. -Clinical response at weeks 12 and 52. -Mucosal healing at weeks 12 and 52. -Adverse events.

Sandborn et al, 2007a [16]

52 sites in the United States, Canada, and Europe

November 2004 to December 2005

Randomized, double-blind, placebo-controlled trial

Induction

325

35%

-Clinical remission at week 4. -Clinical response at week 4. -Adverse events.

Sandborn et al, 2007b [17]

Multi-countries

August 28, 2002 to January 12, 2005

Multi-center, randomized, double-blind, placebo-controlled trial

Maintenance

Clinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn’s Disease (CLASSIC-II)

40%

-Clinical remission at week 56. -Clinical response at week 56. -Adverse events.

Watanabe et al, 2012 [18]

Japan

January 2007 to December 2008

Multicenter, randomized, double-blind, placebo-controlled trial

Induction and maintenance

31.1

59.9%

-Clinical remission at week 4 and 56. -Clinical response at week 4 and 56. -Adverse events.

Sandborn et al, 2013 [19]

285 medical centers in 39 countries

December 2008 to May 2012

Phase 3, randomized, parallel-group, double-blind, placebo-controlled study

Induction and maintenance

GEMINI 2

1115

36.1

46.6%

-Clinical remission at week 6 and 52. -Clinical response at week 6 and 52. -Adverse events.

Sands et al, 2014 [20]

107 sites in North America, Europe, Asia, Africa, and Australia

November 2010 to April 2012

Phase 3, randomized, placebo-controlled, double-blind, multinational, multicenter trial

Induction

GEMINI 3

315

35.8

56.5%

-Clinical remission at week 6 and 10. -Clinical response at week 6 and 10. -Adverse events.

Vermeire et al, 2022 [21]

169 sites in 30 countries

December 2015 to May 2019

Randomized, double-blind, placebo-controlled, phase 3 trial

Maintenance

VISIBLE 2

409

53.2%

-Clinical remission at week 52. -Clinical response at week 52. -Adverse events.

Watanabe et al, 2020 [22]

77 centers in Japan

January 28, 2014 to November 16, 2017

A prospective, multicenter, randomized, double-blind, placebo-controlled phase 3 trial

Induction and maintenance

157

34.6

64%

-Clinical remission at weeks 10 and 60. -Clinical response at weeks 10 and 60. -Adverse events.

Croft et al, 2021 [23]

24 hospitals in 10 countries

January 1, 2014 to December 22, 2020

A double-blind, placebo-controlled phase 3 trial

Induction and maintenance

ENVISION I

14.1

45%

-Clinical remission at weeks 8 and 52. -Clinical response at week 52. -Mucosal healing at week 52. -Adverse events.

Reinisch et al, 2011 [24]

94 centers in North America and Europe

August 2007 to February 2010

Phase III, multicenter, randomized, double-blind, placebo-controlled trial

Induction

390

37.5

62.3%

-Clinical remission at week 8. -Clinical response at week 8. -Mucosal healing at week 8. -Adverse events.

Sandborn et al, 2012 [25]

103 centers in North America, Europe, Australia, New Zealand, and Israel

November 2006 and March 2010

Phase 3, multicenter, randomized, double-blind, placebo-controlled trial

Induction and maintenance

494

40.4

59.5%

-Clinical remission at weeks 8 and 52. -Clinical response at weeks 8 and 52. -Mucosal healing at weeks 8 and 52. -Adverse events.

Suzuki et al, 2014 [26]

Japan

February 2009 to May 2011

Phase II/III, randomized, double-blind, placebo-controlled study

Induction and maintenance

273

42.7

62.7%

-Clinical remission at weeks 8 and 52. -Clinical response at weeks 8 and 52. -Mucosal healing at weeks 8 and 52. -Adverse events.

Feagan et al, 2013 [27]

211 medical centers in 34 countries from 2008 to 2012

2008 to 2012

Phase 3, randomized, double-blind, placebo-controlled study

Induction and maintenance

895

40.3

58.7%

-Clinical remission at weeks 6 and 52. -Clinical response at week 6. -Mucosal healing at weeks 6 and 52. -Adverse events.

Motoya et al, 2019 [28]

86 sites in Japan

February 2014 to November 2015

Phase 3, randomized, double-blind, placebo-controlled study

Induction and maintenance

292

42.9

61.3%

-Clinical remission at weeks 10 and 60. -Clinical response at weeks 10 and 60. -Mucosal healing at weeks 10 and 60.

Sandborn et al, 2020 [29]

141 sites in 29 countries

December 18, 2015 to August 21, 2018

Phase 3, randomized, placebo-controlled, double-blind, double-dummy trial

Maintenance

VISIBLE 1

216

39.7

59.8%

-Clinical response at week 52. -Clinical remission at week 52. -Mucosal healing at week 52. -Adverse events.

**Table 2.** Methodological Quality of Included Studies
Study	The Jadad scores	Total score
1: Was the study carried out using randomization? 2: Did the study provide a clear and suitable description of the randomization process? 3: Was the study characterized as double-blind? 4: Was the blinding procedure described meticulously and aptly? 5: Were details regarding withdrawals and dropouts included?
Chen et al, 2020 [12]	1	0	1	1	1	4
Colombel et al, 2007 [13]	1	0	1	1	1	4
Hanauer et al, 2006 [14]	1	0	1	1	1	4
Rutgeerts et al, 2012 [15]	1	0	1	1	0	3
Sandborn et al, 2007a [16]	1	0	1	1	1	4
Sandborn et al, 2007b [17]	1	0	1	1	1	4
Watanabe et al, 2012 [18]	1	0	1	1	1	4
Sandborn et al, 2013 [19]	1	0	1	1	0	3
Sands et al, 2014 [20]	1	0	1	1	1	4
Vermeire et al, 2022 [21]	1	0	1	1	0	3
Watanabe et al, 2020 [22]	1	0	1	1	0	3
Croft et al, 2021 [23]	1	0	1	1	1	4
Reinisch et al, 2011 [24]	1	0	1	1	0	3
Sandborn et al, 2012 [25]	1	0	1	1	0	3
Suzuki et al, 2014 [26]	1	0	1	1	1	4
Feagan et al, 2013 [27]	1	0	1	1	0	3
Motoya et al, 2019 [28]	1	0	1	1	0	3
Sandborn et al, 2020 [29]	1	0	1	1	1	4

Table 2. Methodological Quality of Included Studies

Study

The Jadad scores

Total score

1: Was the study carried out using randomization? 2: Did the study provide a clear and suitable description of the randomization process? 3: Was the study characterized as double-blind? 4: Was the blinding procedure described meticulously and aptly? 5: Were details regarding withdrawals and dropouts included?

Chen et al, 2020 [12]

Colombel et al, 2007 [13]

Hanauer et al, 2006 [14]

Rutgeerts et al, 2012 [15]

Sandborn et al, 2007a [16]

Sandborn et al, 2007b [17]

Watanabe et al, 2012 [18]

Sandborn et al, 2013 [19]

Sands et al, 2014 [20]

Vermeire et al, 2022 [21]

Watanabe et al, 2020 [22]

Croft et al, 2021 [23]

Reinisch et al, 2011 [24]

Sandborn et al, 2012 [25]

Suzuki et al, 2014 [26]

Feagan et al, 2013 [27]

Motoya et al, 2019 [28]

Sandborn et al, 2020 [29]