1Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan
2Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan
© 2025 Korean Association for the Study of Intestinal Diseases.
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
This work was supported by Takeda Pharmaceutical Company Limited. Takeda Pharmaceutical Company Limited was involved in the study design, data collection, data analysis, and preparation of the manuscript.
Conflict of Interest
Miyoshi J has received honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from AbbVie GK, Janssen Asia Pacific, Janssen Pharmaceuticals K.K., Mitsubishi Tanabe Pharma Co., Ltd., Miyarisan Co., Ltd., and Takeda Pharmaceutical Company Limited. Yoon A is an employee of Takeda Pharmaceutical Company Limited. Matsuura M has received honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from AbbVie GK, EA Pharma Co., Ltd., Janssen Pharmaceuticals K.K., JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co. Ltd., Pfizer Japan Inc., Sandoz AG, Takeda Pharmaceutical Company Limited, Viatris Inc., and ZERIA Pharmaceutical Co., Ltd. In addition, Matsuura M has a leadership or fiduciary role as a member of the Clinical Epidemiology Committee of the Japanese Society for Inflammatory Bowel Disease, a member of the Committee on Public Information of the Japanese Society for Mucosal Immunology, and a Council member of the Japan Small Intestine Society. Hisamatsu T has received grants or contracts from Daiichi Sankyo Co., Ltd., EA Pharma Co., Ltd., JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Nichi-Iko Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Company Limited, and ZERIA Pharmaceutical Co., Ltd.; consulting fees from AbbVie GK, EA Pharma Co., Ltd., Eli Lilly and Company, Gilead, Janssen Pharmaceuticals K.K., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Company Limited; and has received honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from AbbVie GK, EA Pharma Co., Ltd., Gilead, Janssen Pharmaceuticals K.K., JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Company Limited.
Data Availability Statement
The dataset generated and analyzed during the current study is not publicly available because it was used under contract from JMDC Inc., but is available from the corresponding author on reasonable request.
Author Contributions
Conceptualization: Yoon A, Hisamatsu T. Formal analysis: all authors. Investigation: all authors. Writing - original draft: Miyoshi J. Writing - review & editing: all authors. Approval of final manuscript: all authors.
Additional Contributions
The authors thank Yuji Honma (JMDC Inc.) for his contributions to project management of this study, Michinori Arimitsu (JMDC Inc.) for statistical support, and Serina Stretton (Envision Pharma Group) for editorial and medical writing support.
Variable | All patients (n = 823) | No biologics (n = 353) | Biologics (n = 470) | P-valuea |
---|---|---|---|---|
Treatment during 12 mo from index | < 0.001 | |||
5-ASA | ||||
No | 151 (18.3) | 107 (30.3) | 44 (9.4) | |
Yes | 672 (81.7) | 246 (69.7) | 426 (90.6) | < 0.001 |
SCS | ||||
No | 414 (50.3) | 139 (39.4) | 275 (58.5) | |
Yes | 409 (49.7) | 214 (60.6) | 195 (41.5) | 0.324 |
Immunomodulator | ||||
No | 644 (78.3) | 282 (79.9) | 362 (77.0) | |
Yes | 179 (21.7) | 71 (20.1) | 108 (23.0) | < 0.001 |
Enteral nutrition | ||||
No | 236 (28.7) | 128 (36.3) | 108 (23.0) | |
Yes | 587 (71.3) | 225 (63.7) | 362 (77.0) | < 0.001 |
Montreal classification | ||||
≤ 16 yr | 148 (18.0) | 55 (15.6) | 93 (19.8) | |
17–40 yr | 513 (62.3) | 198 (56.1) | 315 (67.0) | |
> 40 yr | 162 (19.7) | 100 (28.3) | 62 (13.2) | 0.088 |
Sex | ||||
Male | 639 (77.6) | 264 (74.8) | 375 (79.8) | |
Female | 184 (22.4) | 89 (25.2) | 95 (20.2) | < 0.001 |
Endoscopy/colonoscopy/MRE within 12 mo from index | ||||
No | 146 (17.7) | 101 (28.6) | 45 (9.6) | |
Yes | 677 (82.3) | 252 (71.4) | 425 (90.4) | < 0.001 |
Perianal lesions within 12 mo from index | ||||
No | 509 (61.8) | 259 (73.4) | 250 (53.2) | |
Yes | 314 (38.2) | 94 (26.6) | 220 (46.8) |
Variable | Biologics (n = 470) | Step-up: SCS prescription before biologics (n = 165) | Top-down: no SCSprescription before biologics (n = 305) | P-valuea |
---|---|---|---|---|
Treatment during 12 mo from index | ||||
5-ASA | 0.417 | |||
No | 44 (9.4) | 13 (7.9) | 31 (10.2) | |
Yes | 426 (90.6) | 152 (92.1) | 274 (89.8) | |
Immunomodulator | 0.003 | |||
No | 362 (77.0) | 114 (69.1) | 248 (81.3) | |
Yes | 108 (23.0) | 51 (30.9) | 57 (18.7) | |
Enteral nutrition | 0.369 | |||
No | 108 (23.0) | 34 (20.6) | 74 (24.3) | |
Yes | 362 (77.0) | 131 (79.4) | 231 (75.7) | |
First biologic since index | ||||
Anti-TNF | 0.007 | |||
No | 86 (18.3) | 41 (24.8) | 45 (14.8) | |
Yes | 384 (81.7) | 124 (75.2) | 260 (85.2) | |
Montreal classification | 0.386 | |||
≤ 16 yr | 93 (19.8) | 37 (22.4) | 56 (18.4) | |
17–40 yr | 315 (67.0) | 110 (66.7) | 205 (67.2) | |
> 40 yr | 62 (13.2) | 18 (10.9) | 44 (14.4) | |
Sex | 0.010 | |||
Male | 375 (79.8) | 121 (73.3) | 254 (83.3) | |
Female | 95 (20.2) | 44 (26.7) | 51 (16.7) | |
Perianal lesions at index | 0.007 | |||
No | 268 (57.0) | 108 (65.5) | 160 (52.5) | |
Yes | 202 (43.0) | 57 (34.5) | 145 (47.5) |
a From the original biologic group (n=490), patients who could be followed for 12 months or longer from initiation of the first-line biologic were selected, excluding those whose first biologic was vedolizumab (n=9) because of the small number of patients in this group.
SD, standard deviation; CI, confidence interval.
Variable | All patients | No biologics |
Biologics |
||||
---|---|---|---|---|---|---|---|
All (n = 353) | SCS: with SCS (n = 214) | No bio/SCS: without SCS (n = 139) | All (n = 470) | Step-up: SCS before biologics (n = 165) | Top-down: no SCS before biologics (n = 305) | ||
Male sex | 639 (77.6) | 264 (74.8) | 157 (73.4) | 107 (77.0) | 375 (79.8) | 121 (73.3) | 254 (83.3) |
Age (yr) | |||||||
Mean ± SD | 28.5 ± 13.6 | 31.7 ± 15.2 | 32.2 ± 15.9 | 30.8 ± 14.0 | 26.0 ± 11.7 | 24.6 ± 11.4 | 26.8 ± 11.8 |
Median (range) | 24 (2–74) | 28 (4–73) | 29 (4–73) | 28 (5–63) | 23 (2–74) | 21 (2–74) | 24 (4–68) |
Age of onset | |||||||
Very early (< 6 yr) | 5 (0.6) | 2 (0.6) | 1 (0.5) | 1 (0.7) | 3 (0.6) | 2 (1.2) | 1 (0.3) |
Pediatric (< 18 yr) | 173 (21.0) | 65 (18.4) | 41 (19.2) | 24 (17.3) | 108 (23.0) | 44 (26.7) | 64 (21.0) |
Adult (≥ 18 to < 60 yr) | 623 (75.7) | 270 (76.5) | 160 (74.8) | 110 (79.1) | 353 (75.1) | 117 (70.9) | 236 (77.4) |
Elderly (≥ 60 yr) | 22 (2.7) | 16 (4.5) | 12 (5.6) | 4 (2.9) | 6 (1.3) | 2 (1.2) | 4 (1.3) |
Montreal classification | |||||||
≤ 16 yr | 148 (18.0) | 55 (15.6) | 35 (16.4) | 20 (14.4) | 93 (19.8) | 37 (22.4) | 56 (18.4) |
17–40 yr | 513 (62.3) | 198 (56.1) | 114 (53.3) | 84 (60.4) | 315 (67.0) | 110 (66.7) | 205 (67.2) |
> 40 yr | 162 (19.7) | 100 (28.3) | 65 (30.4) | 35 (25.2) | 62 (13.2) | 18 (10.9) | 44 (14.4) |
Perianal lesions at index | |||||||
No | 540 (65.6) | 272 (77.1) | 169 (79.0) | 103 (74.1) | 268 (57.0) | 108 (65.5) | 160 (52.5) |
Yes | 283 (34.4) | 81 (22.9) | 45 (21.0) | 36 (25.9) | 202 (43.0) | 57 (34.5) | 145 (47.5) |
Perianal lesions at 12 mo | |||||||
No | 509 (61.8) | 259 (73.4) | 164 (76.6) | 95 (68.3) | 250 (53.2) | 100 (60.6) | 150 (49.2) |
Yes | 314 (38.2) | 94 (26.6) | 50 (23.4) | 44 (31.7) | 220 (46.8) | 65 (39.4) | 155 (50.8) |
CD location at 12 mo | |||||||
Small intestine | 94 (11.4) | 42 (11.9) | 15 (7.0) | 27 (19.4) | 52 (11.1) | 19 (11.5) | 33 (10.8) |
Large intestine | 51 (6.2) | 20 (5.7) | 12 (5.6) | 8 (5.8) | 31 (6.6) | 17 (10.3) | 14 (4.6) |
Small and large intestine | 176 (21.4) | 51 (14.4) | 28 (13.1) | 23 (16.5) | 125 (26.6) | 50 (30.3) | 75 (24.6) |
Unspecified | 502 (61.0) | 240 (68.0) | 159 (74.3) | 81 (58.3) | 262 (55.7) | 79 (47.9) | 183 (60.0) |
Trend analysis period | All patients (n=823) |
Treatment decision |
|||
---|---|---|---|---|---|
No biologics (n = 353) |
Biologics (n = 470) |
||||
No. (%) | No. (%) | 95% CI | No. (%) | 95% CI | |
2010–2011 | 31 (100) | 10 (32.3) | 16.7–51.4 | 21 (67.7) | 48.6–83.3 |
2012–2013 | 46 (100) | 20 (43.5) | 28.9–58.9 | 26 (56.5) | 41.1–71.1 |
2014–2015 | 100 (100) | 44 (44.0) | 34.1–54.3 | 56 (56.0) | 45.7–65.9 |
2016–2017 | 181 (100) | 82 (45.3) | 37.9–52.9 | 99 (54.7) | 47.1–62.1 |
2018–2019 | 292 (100) | 125 (42.8) | 37.1–48.7 | 167 (57.2) | 51.3–62.9 |
2020 | 173 (100) | 72 (41.6) | 34.2–49.3 | 101 (58.4) | 50.7–65.8 |
Trend analysis period | All patients (n=470) |
Treatment decision |
|||
---|---|---|---|---|---|
Step-up: SCS before biologics (n = 165) |
Top-down: no SCS before biologics (n = 305) |
||||
No. (%) | No. (%) | 95% CI | No. (%) | 95% CI | |
2010–2011 | 21 (100) | 5 (23.8) | 8.2–47.2 | 16 (76.2) | 52.8–91.8 |
2012–2013 | 26 (100) | 4 (15.4) | 4.4–34.9 | 22 (84.6) | 65.1–95.6 |
2014–2015 | 56 (100) | 14 (25.0) | 14.4–38.4 | 42 (75.0) | 61.6–85.6 |
2016–2017 | 99 (100) | 23 (23.2) | 15.3–32.8 | 76 (76.8) | 67.2–84.7 |
2018–2019 | 167 (100) | 70 (41.9) | 34.3–49.8 | 97 (58.1) | 50.2–65.7 |
2020 | 101 (100) | 49 (48.5) | 38.4–58.7 | 52 (51.5) | 41.3–61.6 |
Variable | All patients (n = 823) | No biologics (n = 353) | Biologics (n = 470) | P-value |
---|---|---|---|---|
Treatment during 12 mo from index | < 0.001 | |||
5-ASA | ||||
No | 151 (18.3) | 107 (30.3) | 44 (9.4) | |
Yes | 672 (81.7) | 246 (69.7) | 426 (90.6) | < 0.001 |
SCS | ||||
No | 414 (50.3) | 139 (39.4) | 275 (58.5) | |
Yes | 409 (49.7) | 214 (60.6) | 195 (41.5) | 0.324 |
Immunomodulator | ||||
No | 644 (78.3) | 282 (79.9) | 362 (77.0) | |
Yes | 179 (21.7) | 71 (20.1) | 108 (23.0) | < 0.001 |
Enteral nutrition | ||||
No | 236 (28.7) | 128 (36.3) | 108 (23.0) | |
Yes | 587 (71.3) | 225 (63.7) | 362 (77.0) | < 0.001 |
Montreal classification | ||||
≤ 16 yr | 148 (18.0) | 55 (15.6) | 93 (19.8) | |
17–40 yr | 513 (62.3) | 198 (56.1) | 315 (67.0) | |
> 40 yr | 162 (19.7) | 100 (28.3) | 62 (13.2) | 0.088 |
Sex | ||||
Male | 639 (77.6) | 264 (74.8) | 375 (79.8) | |
Female | 184 (22.4) | 89 (25.2) | 95 (20.2) | < 0.001 |
Endoscopy/colonoscopy/MRE within 12 mo from index | ||||
No | 146 (17.7) | 101 (28.6) | 45 (9.6) | |
Yes | 677 (82.3) | 252 (71.4) | 425 (90.4) | < 0.001 |
Perianal lesions within 12 mo from index | ||||
No | 509 (61.8) | 259 (73.4) | 250 (53.2) | |
Yes | 314 (38.2) | 94 (26.6) | 220 (46.8) |
Variable | Reference | Label | OR (95% CI) | P-value |
---|---|---|---|---|
Treatment during 12 mo from index | ||||
5-ASA | No | Yes | 2.58 (1.64–4.06) | < 0.001 |
SCS | No | Yes | 0.52 (0.38–0.70) | < 0.001 |
Immunomodulator | No | Yes | 1.15 (0.80–1.65) | 0.443 |
Enteral nutrition | No | Yes | 0.88 (0.61–1.28) | 0.495 |
Montreal classification | 17–40 yr | ≤ 16 yr | 1.12 (0.75–1.68) | 0.579 |
> 40 yr | 0.50 (0.33–0.75) | < 0.001 | ||
Sex | Female | Male | 0.92 (0.63–1.33) | 0.637 |
Endoscopy/colonoscopy/MRE within 12 mo from index | No | Yes | 2.10 (1.35–3.28) | 0.001 |
Perianal lesions within 12 mo from index | No | Yes | 1.53 (1.10–2.13) | 0.011 |
Variable | Biologics (n = 470) | Step-up: SCS prescription before biologics (n = 165) | Top-down: no SCSprescription before biologics (n = 305) | P-value |
---|---|---|---|---|
Treatment during 12 mo from index | ||||
5-ASA | 0.417 | |||
No | 44 (9.4) | 13 (7.9) | 31 (10.2) | |
Yes | 426 (90.6) | 152 (92.1) | 274 (89.8) | |
Immunomodulator | 0.003 | |||
No | 362 (77.0) | 114 (69.1) | 248 (81.3) | |
Yes | 108 (23.0) | 51 (30.9) | 57 (18.7) | |
Enteral nutrition | 0.369 | |||
No | 108 (23.0) | 34 (20.6) | 74 (24.3) | |
Yes | 362 (77.0) | 131 (79.4) | 231 (75.7) | |
First biologic since index | ||||
Anti-TNF | 0.007 | |||
No | 86 (18.3) | 41 (24.8) | 45 (14.8) | |
Yes | 384 (81.7) | 124 (75.2) | 260 (85.2) | |
Montreal classification | 0.386 | |||
≤ 16 yr | 93 (19.8) | 37 (22.4) | 56 (18.4) | |
17–40 yr | 315 (67.0) | 110 (66.7) | 205 (67.2) | |
> 40 yr | 62 (13.2) | 18 (10.9) | 44 (14.4) | |
Sex | 0.010 | |||
Male | 375 (79.8) | 121 (73.3) | 254 (83.3) | |
Female | 95 (20.2) | 44 (26.7) | 51 (16.7) | |
Perianal lesions at index | 0.007 | |||
No | 268 (57.0) | 108 (65.5) | 160 (52.5) | |
Yes | 202 (43.0) | 57 (34.5) | 145 (47.5) |
Variable | Reference | Label | OR (95% CI) | P-value |
---|---|---|---|---|
Treatment during 12 mo from index | ||||
5-ASA | No | Yes | 1.37 (0.67–2.81) | 0.387 |
Immunomodulator | No | Yes | 2.24 (1.41–3.56) | < 0.001 |
Enteral nutrition | No | Yes | 1.09 (0.67–1.78) | 0.725 |
Type of biologic | ||||
Anti-TNF | No | Yes | 0.46 (0.28–0.76) | 0.003 |
Montreal classification | 17–40 yr | ≤ 16 yr | 1.32 (0.79–2.18) | 0.288 |
> 40 yr | 0.53 (0.28–1.01) | 0.054 | ||
Sex | Female | Male | 0.60 (0.37–0.99) | 0.045 |
Perianal lesions within 12 mo from index | No | Yes | 0.60 (0.40–0.90) | 0.014 |
Group | Time (mo), mean ± SD | 95% CI |
---|---|---|
Modified biologic group (n = 420) | ||
Infliximab (n = 185) | 1.8 ± 2.3 | 1.5–2.1 |
Adalimumab (n = 170) | 2.5 ± 2.4 | 2.2–2.9 |
Ustekinumab (n = 65) | 3.6 ± 3.0 | 2.8–4.3 |
Modified step-up group (n = 138) | ||
Infliximab (n = 56) | 2.0 ± 2.5 | 1.3–2.7 |
Adalimumab (n = 53) | 3.0 ± 2.4 | 2.4–3.7 |
Ustekinumab (n = 29) | 3.7 ± 3.1 | 2.5–4.9 |
Modified top-down group (n = 282) | ||
Infliximab (n = 129) | 1.7 ± 2.2 | 1.3–2.1 |
Adalimumab (n = 117) | 2.3 ± 2.4 | 1.8–2.7 |
Ustekinumab (n = 36) | 3.4 ± 3.0 | 2.4–4.5 |
Values are presented as number (%) unless indicated otherwise. SCS, systemic corticosteroid; SD, standard deviation; CD, Crohn’s disease.
CI, confidence interval.
SCS, systemic corticosteroid; CI, confidence interval.
Values are presented as number (%). Chi-square test. 5-ASA, 5-acetylsalicylic acid; SCS, systemic corticosteroid; MRE, magnetic resonance enterography.
Logistic regression. OR, odds ratio; CI, confidence interval; 5-ASA, 5-acetylsalicylic acid; SCS, systemic corticosteroid; MRE, magnetic resonance enterography.
Values are presented as number (%). Chi-square test. 5-ASA, 5-acetylsalicylic acid; SCS, systemic corticosteroid; TNF, tumor necrosis factor.
Values are presented as number (%) unless indicated otherwise. Logistic regression. OR, odds ratio; CI, confidence interval; SCS, systemic corticosteroid; 5-ASA, 5-acetylsalicylic acid; TNF, tumor necrosis factor.
From the original biologic group (n=490), patients who could be followed for 12 months or longer from initiation of the first-line biologic were selected, excluding those whose first biologic was vedolizumab (n=9) because of the small number of patients in this group. SD, standard deviation; CI, confidence interval.