1Asian Institute of Gastroenterology, Hyderabad, India
2Singapore General Hospital, Singapore
3University Malaya Medical Centre, Kuala Lumpur, Malaysia
4Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
5University of Ulsan College of Medicine, Seoul, Korea
6Takeda Pharmaceutical International AG, Singapore
7Takeda Pharmaceutical International AG, Zurich, Switzerland
© Copyright 2021. Korean Association for the Study of Intestinal Diseases. All rights reserved.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Funding Source
The study was funded by Takeda Pharmaceuticals Company Ltd.
Conflict of Interest
Clinical trials were sponsored and conducted by Takeda Pharmaceuticals Company Ltd. Medical writing support was sponsored by Takeda Pharmaceuticals Company Ltd. Demuth D, Lindner D, and Adsul S are employees of Takeda Pharmaceuticals Company Ltd. The other authors report no conflict of interest.
Author Contribution
Conceptualization: Banerjee R, Hilmi IN, Wu DC, Demuth D, Lindner D, Adsul S. Methodology: Banerjee R, Hilmi IN, Wu DC, Demuth D, Lindner D, Adsul S. Formal analysis: Demuth D, Lindner D, Adsul S. Project administration: Banerjee R, Hilmi IN, Demuth D, Lindner D, Adsul S. Visualization: Banerjee R, Hilmi IN, Wu DC, Demuth D, Lindner D, Adsul S. Writing - original draft: Demuth D, Lindner D, Adsul S. Writing - review and editing: Banerjee R, Hilmi IN, Wu DC, Demuth D, Lindner D, Adsul S. Approval of final manuscript: all authors.
Others
The authors thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. Medical writing support was provided by Assansa, India (a Healthcare Consultancy-Assansa consultants Dr. Aamir Shaikh MD, Dr. Saifuddin Kharawala MBBS, DPM) and sponsored by Takeda Pharmaceuticals Company Ltd.
Values are presented as number (%), mean±standard deviation, or median (range).
Placebo and vedolizumab (cohort 1)=the groups that were part of the double-blind induction phase (induction intent-to-treat [ITT] population); Vedolizumab (cohort 2)=additional patients were enrolled to meet the maintenance phase sample size requirements and received open-label vedolizumab (induction safety population only); Vedolizumab (combined)=all patients that received vedolizumab during the induction phase.
CD, Crohn’s disease; TNF, tumor necrosis factor; CDAI, Crohn’s Disease Activity Index.
Parameter |
ITT |
Non-ITT |
Placebo combined | Vedolizumab combined | ||||
---|---|---|---|---|---|---|---|---|
Placebo | Vedolizumab q8w | Vedolizumab q4w | Placeboa | Vedolizumab q4wa | ||||
No. | 7 | 11 | 12 | 17 | 28 | 24 | 51 | |
Male sex | 3 (43) | 6 (55) | 8 (67) | 7 (41) | 19 (68) | 10 (42) | 33 (65) | |
Age (yr) | 34.5 ± 4.7 | 38.8 ± 13.2 | 27.2 ± 6.5 | 32.4 ± 8.7 | 30.0 ± 8.9 | 33.0 ± 7.7 | 31.3 ± 10.2 | |
Body weight (kg) | 46.0 ± 11.7 | 51.2 ± 9.3 | 53.7 ± 7.6 | 53.4 ± 15.9 | 49.0 ± 10.8 | 51.2 ± 15.0 | 50.6 ± 9.8 | |
Duration of CD (yr) | 3.1 (1.1–11.1) | 4.1 (1.1–14.0) | 4.1 (0.6–14.2) | 2.7 (0.7–9.9) | 3.4 (0.5–13.8) | 2.9 (0.7–11.1) | 3.7 (0.5–14.2) | |
Concomitant medications for CD | ||||||||
Only glucocorticoids | 1 (14) | 2 (18) | 2 (17) | 2 (12) | 6 (21) | 3 (13) | 10 (20) | |
Only immunomodulators | 1 (14) | 3 (27) | 5 (42) | 2 (12) | 5 (18) | 3 (13) | 13 (25) | |
Glucocorticoids and immunomodulators | 2 (29) | 3 (27) | 3 (25) | 6 (35) | 5 (18) | 8 (33) | 11 (22) | |
No glucocorticoids or immunomodulators | 3 (43) | 3 (27) | 2 (17) | 7 (41) | 12 (43) | 10 (42) | 17 (33) | |
Patients with prior anti-TNF use | 0 | 2 (18) | 2 (17) | 4 (24) | 7 (25) | 4 (17) | 11 (22) | |
Patients with prior anti-TNF failure | 0 | 1 (9) | 1 (8) | 4 (24) | 7 (25) | 4 (17) | 9 (18) | |
CDAI score | 329 ± 82 | 326 ± 80 | 310 ± 97 | 349 ± 82 | 347 ± 77 | 343 ± 81 | 334 ± 83 |
83Values are presented as number (%), mean±standard deviation, or median (range).
Intent-to-treat (ITT)=patients who showed response to vedolizumab at 6 weeks and were randomized as part of the double-blind maintenance phase (maintenance ITT population); Non-ITT placebo=patients that were randomized to placebo during the induction phase and continued to received double-blind placebo during maintenance phase (maintenance safety population only); Non-ITT vedolizumab q4w=patients that did not show response to vedolizumab at 6 weeks and received open-label vedolizumab during the maintenance phase (maintenance safety population only); Placebo combined=all patients that received placebo during the maintenance phase; Vedolizumab combined=all patients that received vedolizumab during the maintenance phase.
a Patient numbers do not exactly match those shown in disposition (Fig. 1) because those patients who were discontinued from the study during the induction phase continued to be included in the safety population and have been counted within these groups.
q4w, every 4 weeks; q8w, every 8 weeks; CD, Crohn’s disease; TNF, tumor necrosis factor; CDAI, Crohn’s Disease Activity Index.
Values are presented as number (%), mean±standard deviation, or median (range).
Placebo and vedolizumab (cohort 1)=the groups that were part of the double-blind induction phase (induction intent-to-treat [ITT] population); Vedolizumab (cohort 2)=additional patients were enrolled to meet the maintenance phase sample size requirements and received open-label vedolizumab (induction safety population only); Vedolizumab (combined)=all patients that received vedolizumab during the induction phase.
CD, Crohn’s disease; TNF, tumor necrosis factor; CDAI, Crohn’s Disease Activity Index.
Parameter |
ITT |
Non-ITT |
Placebo combined | Vedolizumab combined | ||||
---|---|---|---|---|---|---|---|---|
Placebo | Vedolizumab q8w | Vedolizumab q4w | Placeboa | Vedolizumab q4wa | ||||
No. | 146 | 143 | 142 | 131 | 478 | 277 | 763 | |
Male sex | 69 (47) | 62 (43) | 74 (52) | 62 (47) | 210 (44) | 131 (47) | 346 (45) | |
Age (yr) | 37.4 ± 12.2 | 34.8 ± 12.2 | 35.6 ± 12.4 | 39.4 ± 13.5 | 36.1 ± 11.8 | 38.3 ± 12.8 | 35.7 ± 12.0 | |
Body weight (kg) | 70.1 ± 17.7 | 69.9 ± 18.4 | 73.0 ± 18.2 | 70.7 ± 18.4 | 71.4 ± 20.3 | 70.4 ± 18.0 | 71.4 ± 19.6 | |
Duration of CD (yr) | 7.4 (0.3–43.6) | 6.5 (0.3–34.7) | 6.8 (0.2–42.5) | 6.6 (0.3–42.0) | 8.5 (0.3–42.8) | 6.9 (0.3–43.6) | 7.6 (0.2–42.8) | |
Concomitant medications for CD | ||||||||
Only glucocorticoids | 55 (38) | 57 (40) | 56 (39) | 43 (33) | 157 (33) | 98 (35) | 270 (35) | |
Only immunomodulators | 22 (15) | 24 (17) | 26 (18) | 23 (18) | 70 (15) | 45 (16) | 120 (16) | |
Glucocorticoids and immunomodulators | 24 (16) | 20 (14) | 19 (13) | 20 (15) | 87 (18) | 44 (16) | 126 (17) | |
No glucocorticoids or immunomodulators | 45 (31) | 42 (29) | 41 (29) | 45 (34) | 164 (34) | 90 (32) | 247 (32) | |
Patients with prior anti-TNF use | 82 (56) | 86 (60) | 81 (57) | 68 (52) | 357 (75) | 150 (54) | 524 (69) | |
Patients with prior anti-TNF failure | 78 (53) | 81 (57) | 76 (54) | 66 (50) | 331 (69) | 144 (52) | 488 (64) | |
CDAI score | 325 ± 65 | 326 ± 68 | 318 ± 63 | 322 ± 77 | 323 ± 69 | 323 ± 71 | 322 ± 67 |
Values are presented as number (%), mean±standard deviation, or median (range).
Intent-to-treat (ITT)=patients who showed response to vedolizumab at 6 weeks and were randomized as part of the double-blind maintenance phase (maintenance ITT population); Non-ITT placebo=patients that were randomized to placebo during the induction phase and continued to received double-blind placebo during maintenance phase (maintenance safety population only); Non-ITT vedolizumab q4w=patients that did not show response to vedolizumab at 6 weeks and received open-label vedolizumab during the maintenance phase (maintenance safety population only); Placebo combined=all patients that received placebo during the maintenance phase; Vedolizumab combined=all patients that received vedolizumab during the maintenance phase.
a Patient numbers do not exactly match those shown in disposition (Fig. 1) because those patients who were discontinued from the study during the induction phase continued to be included in the safety population and have been counted within these groups.
q4w, every 4 weeks; q8w, every 8 weeks; CD, Crohn’s disease; TNF, tumor necrosis factor; CDAI, Crohn’s Disease Activity Index.
Parameter | Placebo | Vedolizumab (cohort 1) | Vedolizumab (cohort 2) | Vedolizumab (combined) |
---|---|---|---|---|
No. | 17 | 34 | 24 | 58 |
Male sex | 7 (41) | 20 (59) | 16 (67) | 36 (62) |
Age (yr) | 32.4 ± 8.7 | 32.4 ± 10.6 | 30.5 ± 8.5 | 31.6 ± 9.8 |
Body weight (kg) | 53.4 ± 15.9 | 49.0 ± 10.0 | 51.5 ± 10.3 | 50.0 ± 10.1 |
Duration of CD (yr) | 2.7 (0.7–9.9) | 2.9 (0.5–14.2) | 3.6 (1.1–14.0) | 3.4 (0.5–14.2) |
Concomitant medications for CD | ||||
Only glucocorticoids | 2 (12) | 6 (18) | 5 (21) | 11 (19) |
Only immunomodulators | 2 (12) | 8 (24) | 6 (25) | 14 (24) |
Glucocorticoids and immunomodulators | 6 (35) | 7 (21) | 6 (25) | 13 (22) |
No glucocorticoids or immunomodulators | 7 (41) | 13 (38) | 7 (29) | 20 (34) |
Patients with prior anti-TNF use | 4 (24) | 5 (15) | 6 (25) | 11 (19) |
Patients with prior anti-TNF failure | 4 (24) | 4 (12) | 5 (21) | 9 (16) |
CDAI score | 349 ± 82 | 343 ± 89 | 320 ± 69 | 333 ± 82 |
Parameter | ITT |
Non-ITT |
Placebo combined | Vedolizumab combined | ||||
---|---|---|---|---|---|---|---|---|
Placebo | Vedolizumab q8w | Vedolizumab q4w | Placebo |
Vedolizumab q4w |
||||
No. | 7 | 11 | 12 | 17 | 28 | 24 | 51 | |
Male sex | 3 (43) | 6 (55) | 8 (67) | 7 (41) | 19 (68) | 10 (42) | 33 (65) | |
Age (yr) | 34.5 ± 4.7 | 38.8 ± 13.2 | 27.2 ± 6.5 | 32.4 ± 8.7 | 30.0 ± 8.9 | 33.0 ± 7.7 | 31.3 ± 10.2 | |
Body weight (kg) | 46.0 ± 11.7 | 51.2 ± 9.3 | 53.7 ± 7.6 | 53.4 ± 15.9 | 49.0 ± 10.8 | 51.2 ± 15.0 | 50.6 ± 9.8 | |
Duration of CD (yr) | 3.1 (1.1–11.1) | 4.1 (1.1–14.0) | 4.1 (0.6–14.2) | 2.7 (0.7–9.9) | 3.4 (0.5–13.8) | 2.9 (0.7–11.1) | 3.7 (0.5–14.2) | |
Concomitant medications for CD | ||||||||
Only glucocorticoids | 1 (14) | 2 (18) | 2 (17) | 2 (12) | 6 (21) | 3 (13) | 10 (20) | |
Only immunomodulators | 1 (14) | 3 (27) | 5 (42) | 2 (12) | 5 (18) | 3 (13) | 13 (25) | |
Glucocorticoids and immunomodulators | 2 (29) | 3 (27) | 3 (25) | 6 (35) | 5 (18) | 8 (33) | 11 (22) | |
No glucocorticoids or immunomodulators | 3 (43) | 3 (27) | 2 (17) | 7 (41) | 12 (43) | 10 (42) | 17 (33) | |
Patients with prior anti-TNF use | 0 | 2 (18) | 2 (17) | 4 (24) | 7 (25) | 4 (17) | 11 (22) | |
Patients with prior anti-TNF failure | 0 | 1 (9) | 1 (8) | 4 (24) | 7 (25) | 4 (17) | 9 (18) | |
CDAI score | 329 ± 82 | 326 ± 80 | 310 ± 97 | 349 ± 82 | 347 ± 77 | 343 ± 81 | 334 ± 83 |
CRP level | Placebo | Vedolizumab |
---|---|---|
All patients | ||
No. | 17 | 34 |
Baseline | 28.9 ± 35.9 | 36.6 ± 38.0 |
Week 6 | 16.2 ± 13.5 | 38.0 ± 38.5 |
Change from baseline | –12.7 ± 34.5 | 1.4 ± 18.6 |
Median change from baseline | –3.6 | 0.2 |
10th and 90th percentile | (–27.6, 4.1) | (–15.0, 10.1) |
Patients with baseline CRP > 2.87 mg/L | ||
No. | 16 | 31 |
Baseline | 30.7 ± 36.3 | 40.0 ± 38.0 |
Week 6 | 17.2 ± 13.3 | 41.6 ± 38.5 |
Change from baseline | –13.5 ± 35.4 | 1.5 ± 19.5 |
Median change from baseline | –4.0 | 0.0 |
10th and 90th percentile | (–27.6, 4.1) | (–15.0, 10.1) |
Parameter | Placebo | Vedolizumab (cohort 1) | Vedolizumab (cohort 2) | Vedolizumab (combined) | |
---|---|---|---|---|---|
No. | 131 | 186 | 723 | 909 | |
Male sex | 62 (47) | 85 (46) | 330 (46) | 415 (46) | |
Age (yr) | 39.4 ± 13.5 | 37.0 ± 11.6 | 35.7 ± 12.1 | 36.0 ± 12.0 | |
Body weight (kg) | 70.7 ± 18.4 | 70.4 ± 18.5 | 71.4 ± 19.5 | 71.2 ± 19.3 | |
Duration of CD (yr) | 6.6 (0.3–42.0) | 8.0 (0.5–43.6) | 7.5 (0.2–42.5) | 7.6 (0.2–43.6) | |
Concomitant medications for CD | |||||
Only glucocorticoids | 43 (33) | 61 (33) | 264 (37) | 325 (36) | |
Only immunomodulators | 23 (18) | 29 (16) | 113 (16) | 142 (16) | |
Glucocorticoids and immunomodulators | 20 (15) | 31 (17) | 119 (16) | 150 (17) | |
No glucocorticoids or immunomodulators | 45 (34) | 65 (35) | 227 (31) | 292 (32) | |
Patients with prior anti-TNF use | 68 (52) | 106 (57) | 500 (69) | 606 (67) | |
Patients with prior anti-TNF failure | 66 (50) | 101 (54) | 465 (64) | 566 (62) | |
CDAI score | 322 ± 77 | 325 ± 67 | 322 ± 67 | 323 ± 67 |
Parameter | ITT |
Non-ITT |
Placebo combined | Vedolizumab combined | ||||
---|---|---|---|---|---|---|---|---|
Placebo | Vedolizumab q8w | Vedolizumab q4w | Placebo |
Vedolizumab q4w |
||||
No. | 146 | 143 | 142 | 131 | 478 | 277 | 763 | |
Male sex | 69 (47) | 62 (43) | 74 (52) | 62 (47) | 210 (44) | 131 (47) | 346 (45) | |
Age (yr) | 37.4 ± 12.2 | 34.8 ± 12.2 | 35.6 ± 12.4 | 39.4 ± 13.5 | 36.1 ± 11.8 | 38.3 ± 12.8 | 35.7 ± 12.0 | |
Body weight (kg) | 70.1 ± 17.7 | 69.9 ± 18.4 | 73.0 ± 18.2 | 70.7 ± 18.4 | 71.4 ± 20.3 | 70.4 ± 18.0 | 71.4 ± 19.6 | |
Duration of CD (yr) | 7.4 (0.3–43.6) | 6.5 (0.3–34.7) | 6.8 (0.2–42.5) | 6.6 (0.3–42.0) | 8.5 (0.3–42.8) | 6.9 (0.3–43.6) | 7.6 (0.2–42.8) | |
Concomitant medications for CD | ||||||||
Only glucocorticoids | 55 (38) | 57 (40) | 56 (39) | 43 (33) | 157 (33) | 98 (35) | 270 (35) | |
Only immunomodulators | 22 (15) | 24 (17) | 26 (18) | 23 (18) | 70 (15) | 45 (16) | 120 (16) | |
Glucocorticoids and immunomodulators | 24 (16) | 20 (14) | 19 (13) | 20 (15) | 87 (18) | 44 (16) | 126 (17) | |
No glucocorticoids or immunomodulators | 45 (31) | 42 (29) | 41 (29) | 45 (34) | 164 (34) | 90 (32) | 247 (32) | |
Patients with prior anti-TNF use | 82 (56) | 86 (60) | 81 (57) | 68 (52) | 357 (75) | 150 (54) | 524 (69) | |
Patients with prior anti-TNF failure | 78 (53) | 81 (57) | 76 (54) | 66 (50) | 331 (69) | 144 (52) | 488 (64) | |
CDAI score | 325 ± 65 | 326 ± 68 | 318 ± 63 | 322 ± 77 | 323 ± 69 | 323 ± 71 | 322 ± 67 |
Values are presented as number (%), mean±standard deviation, or median (range). Placebo and vedolizumab (cohort 1)=the groups that were part of the double-blind induction phase (induction intent-to-treat [ITT] population); Vedolizumab (cohort 2)=additional patients were enrolled to meet the maintenance phase sample size requirements and received open-label vedolizumab (induction safety population only); Vedolizumab (combined)=all patients that received vedolizumab during the induction phase. CD, Crohn’s disease; TNF, tumor necrosis factor; CDAI, Crohn’s Disease Activity Index.
83Values are presented as number (%), mean±standard deviation, or median (range). Intent-to-treat (ITT)=patients who showed response to vedolizumab at 6 weeks and were randomized as part of the double-blind maintenance phase (maintenance ITT population); Non-ITT placebo=patients that were randomized to placebo during the induction phase and continued to received double-blind placebo during maintenance phase (maintenance safety population only); Non-ITT vedolizumab q4w=patients that did not show response to vedolizumab at 6 weeks and received open-label vedolizumab during the maintenance phase (maintenance safety population only); Placebo combined=all patients that received placebo during the maintenance phase; Vedolizumab combined=all patients that received vedolizumab during the maintenance phase. Patient numbers do not exactly match those shown in disposition (Fig. 1) because those patients who were discontinued from the study during the induction phase continued to be included in the safety population and have been counted within these groups. q4w, every 4 weeks; q8w, every 8 weeks; CD, Crohn’s disease; TNF, tumor necrosis factor; CDAI, Crohn’s Disease Activity Index.
Values are presented as mean±standard deviation or unless otherwise stated. CRP, C-reactive protein.
Values are presented as number (%), mean±standard deviation, or median (range). Placebo and vedolizumab (cohort 1)=the groups that were part of the double-blind induction phase (induction intent-to-treat [ITT] population); Vedolizumab (cohort 2)=additional patients were enrolled to meet the maintenance phase sample size requirements and received open-label vedolizumab (induction safety population only); Vedolizumab (combined)=all patients that received vedolizumab during the induction phase. CD, Crohn’s disease; TNF, tumor necrosis factor; CDAI, Crohn’s Disease Activity Index.
Values are presented as number (%), mean±standard deviation, or median (range). Intent-to-treat (ITT)=patients who showed response to vedolizumab at 6 weeks and were randomized as part of the double-blind maintenance phase (maintenance ITT population); Non-ITT placebo=patients that were randomized to placebo during the induction phase and continued to received double-blind placebo during maintenance phase (maintenance safety population only); Non-ITT vedolizumab q4w=patients that did not show response to vedolizumab at 6 weeks and received open-label vedolizumab during the maintenance phase (maintenance safety population only); Placebo combined=all patients that received placebo during the maintenance phase; Vedolizumab combined=all patients that received vedolizumab during the maintenance phase. Patient numbers do not exactly match those shown in disposition (Fig. 1) because those patients who were discontinued from the study during the induction phase continued to be included in the safety population and have been counted within these groups. q4w, every 4 weeks; q8w, every 8 weeks; CD, Crohn’s disease; TNF, tumor necrosis factor; CDAI, Crohn’s Disease Activity Index.