Effect of elemental diet combined with infliximab dose escalation in patients with Crohn's disease with loss of response to infliximab: CERISIER trial

Tadakazu Hisamatsu; Reiko Kunisaki; Shiro Nakamura; Tomoyuki Tsujikawa; Fumihito Hirai; Hiroshi Nakase; Kenji Watanabe; Kaoru Yokoyama; Masakazu Nagahori; Takanori Kanai; Makoto Naganuma; Hirofumi Michimae; Akira Andoh; Akihiro Yamada; Tadashi Yokoyama; Noriko Kamata; Shinji Tanaka; Yasuo Suzuki; Toshifumi Hibi; Mamoru Watanabe; CERISIER Trial group

doi:10.5217/ir.2018.16.3.494

Articles

Page Path: HOME > Intest Res > Volume 16(3); 2018 > Article

Brief Communication Effect of elemental diet combined with infliximab dose escalation in patients with Crohn's disease with loss of response to infliximab: CERISIER trial: Tadakazu Hisamatsu¹, Reiko Kunisaki², Shiro Nakamura³, Tomoyuki Tsujikawa⁴, Fumihito Hirai⁵, Hiroshi Nakase⁶, Kenji Watanabe^7,8, Kaoru Yokoyama⁹, Masakazu Nagahori¹⁰, Takanori Kanai¹¹, Makoto Naganuma¹¹, Hirofumi Michimae¹², Akira Andoh¹³, Akihiro Yamada¹⁴, Tadashi Yokoyama¹⁵, Noriko Kamata¹⁶, Shinji Tanaka¹⁷, Yasuo Suzuki¹⁴, Toshifumi Hibi¹⁸, Mamoru Watanabe¹⁰, CERISIER Trial group; Intestinal Research 2018;16(3):494-498.
DOI: https://doi.org/10.5217/ir.2018.16.3.494
Published online: July 27, 2018

¹The Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka, Japan.

²Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan.

³Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Nishinomiya, Japan.

⁴Department of Gastroenterology and Hepatology, National Hospital Organization, Higashi-Ohmi Medical Center, Higashi-Ohmi, Japan.

⁵Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan.

⁶Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan.

⁷Division of Gastroenterology, Osaka City General Hospital, Osaka, Japan.

⁸Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Japan.

⁹Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan.

¹⁰Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.

¹¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

¹²Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, Tokyo, Japan.

¹³Division of Gastroenterology, Shiga University of Medical Science, Otsu, Japan.

¹⁴Department of Internal Medicine, Toho University Sakura Medical Centre, Sakura, Japan.

¹⁵Yokoyama IBD Clinic, Aichi, Japan.

¹⁶Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

¹⁷Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan.

¹⁸Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.

Correspondence to Tadakazu Hisamatsu, Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka 181-8611, Japan. Tel: +81-422-47-5511 (ext. 5729), Fax: +81-422-71-5381, thisamatsu@ks.kyorin-u.ac.jp

*These authors contributed equally to this study.
#Combination of Elemental Dietary Therapy and Infliximab for Secondary Failure to Infliximab in Patients with Crohn's Disease (CERISIER) Trial group members: Hideaki Kimura2, Shingo Kato19, Shigeki Bamba13, Yuji Naito20, Takuya Inoue21, Shuhei Hosomi16, Masaki Iimuro3, Akira Harada22, Takahiro Beppu519Department of Gastroenterology and Hepatology, Saitama Medical Centre, Saitama Medical University, Kawagoe, 20Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 212nd Department of Internal Medicine, Osaka Medical College, Takatsuki, 22Division of Gastroenterology, Matsuyama Red Cross Hospital, Matsuyama, Japan

• Received: October 23, 2017 • Revised: December 29, 2017 • Accepted: January 9, 2018

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.

prev next

6,468 Views
143 Download
18 Web of Science
19 Crossref
18 Scopus

Full Article

Download PDF

Acknowledgments
ACKNOWLEDGEMENTS
NOTES
SUPPLEMENTARY MATERIALS
REFERENCES

The development and success of anti-tumor necrosis factor-α (anti-TNF-α) monoclonal antibodies (mAbs) have dramatically changed the therapeutic strategy of IBD and contributed to improvements in patients' quality of life.1 Many clinical observations have confirmed that anti-TNF-α mAbs are efficacious for the treatment of CD. Unfortunately, however, we are faced with a new complication: loss of response (LOR). In Japan at the time of this study, an infliximab (IFX) dose escalation regimen to 10 mg/kg was only allowed in patients who developed LOR during scheduled maintenance therapy with IFX (5 mg/kg every 8 weeks) according to the results of a preapproval clinical trial. However, we often encounter patients who cannot gain adequate control with increasing doses of 10 mg/kg of IFX in daily clinical practice. In this open-labeled prospective study (UMIN registration No. 000010058), patients with non-colonic CD who had developed LOR to scheduled administration of IFX (5 mg/kg every 8 weeks) were randomly assigned to IFX dose escalation (10 mg/kg every 8 weeks) with (combination group) or without (monotherapy group) an elemental diet (ED, 900–1200 kcal/day) for 56 weeks (Table 1, Supplementary Figs. 1 and 2). The study was approved by the Institutional Review Board of Keio University Hospital (IRB No. 20120438) and performed in accordance with the principles of the Declaration of Helsinki. The informed consent was written informed consents were obtained. The primary endpoint was the retention rate of IFX dose escalation therapy at week 56. Safety, the CDAI, and the serum albumin and CRP levels at each observation point were analyzed. Intermediate analysis was performed on 15 patients enrolled by 31 March 2015. At week 16, 8 of 11 patients in the combination group and 0 of 4 patients in the monotherapy group showed a CDAI reduction from baseline (ΔCDAI) of ≥50. The intermediate analysis showed the benefits of combination therapy and disadvantage of monotherapy, and the study was stopped. Subsequent analysis showed that the proportion of patients with ΔCDAI of ≥50 (Fig. 1A) and clinical remission (Fig. 1B) at each observation point tended to be higher in the combination group. Compared with the monotherapy group, the combination group showed a tendency toward a superior persistence rate of IFX (10 mg/kg every 8 weeks) at week 56 as the primary endpoint in both the per-protocol set analysis (P=0.1066) and full analysis set analysis (P=0.1629) (Fig. 2). No serious adverse events were observed in either group (Supplementary Table 1). This appears to be the first clinical trial to show the usefulness of combination therapy of enteral nutrition (EN) therapy with biologics for refractory CD.

The effectiveness of EN therapy in patients with CD, especially for the maintenance of clinical remission, has been previously reported.2 3 4 Several recent reports have described combination therapy involving anti-TNF-α mAb therapy with EN therapy. Hirai et al.5 examined 102 patients with CD who were treated with IFX. The cumulative remission rate was significantly higher in the combination therapy group (IFX+EN) than in the non-EN group. Kamata et al.6 reported that concomitant ED therapy (≥900 kcal/day) with IFX scheduled maintenance therapy prevented LOR. Sazuka et al.7 also reported the benefit of concomitant use of EN therapy (≥600 kcal/day) with IFX scheduled maintenance therapy. Sugita et al.8 reported that ED therapy administered concomitantly with adalimumab reduced LOR to adalimumab in IFX-intolerant or IFX-refractory patients. Nguyen et al.9 performed a meta-analysis based on these reports and concluded that in patients with moderate to severe CD undergoing IFX therapy, combined EN therapy of ≥600 kcal/day affected the increase in the remission maintenance rate. In contrast, Yamamoto et al.10 reported the results of a prospective study showing that concomitant EN during IFX maintenance therapy did not show a beneficial effect in the maintenance rate of clinical remission in patients with CD. However, in the EN combination group, the CDAI tended to be lower at each observation time point than in the IFX alone group. In the study by Yamamoto et al.,10 the patients with CD had been newly introduced to IFX. These findings may suggest that IFX and EN combination therapy should be considered in only selected patients, including those with suspected LOR to IFX.

There are several limitations in this study. First, we discontinued this study after obtaining the results of the interim analysis, which actually resulted in statistical underpowering of this investigation. Second, the protocol of this study did not include evaluation of endoscopic activity. Third, maintenance of the relatively high acceptance rate of taking ED in the combination group was influenced by the enrollment of only patients who had appropriate adherence to ED, as judged by the acceptability test before enrollment and the patients' history. Therefore, in daily clinical practice, adherence to oral ED administration is expected to be lower. Improvement of adherence to therapy is an important point when using ED to treat CD.

Acknowledgments

ACKNOWLEDGEMENTS

The authors would like to thank all CERISIER Trial collaborators, investigators, and patients for their participation and contribution to this study. The authors also thank Dr. Fumiaki Ueno, PhD from the Center for Gastroenterology and Inflammatory Bowel Disease, Ofuna Chuo Hospital, Kamakura, Kanagawa, Japan and Prof. Kitaro Futami, PhD from the Department of Surgery, Fukuoka University Chikushi Hospital, Chikushino City, Fukuoka, Japan for their clinical review of the efficacy and adverse events of this trial as the Data and Safety Monitoring Board. The authors thank the Japanese Society for Inflammatory Bowel Disease and EA Pharma Co., Ltd. for supporting the implementation system of this study. The authors thank Angela Morben, DVM, ELS, from Edanz Group (www.edanzediting.com/ac), for editing a draft of this manuscript.

Members of CERISIER Study Group

Satoshi Motoya (Sapporo Kosei General Hospital), Atsuo Maemoto (Sapporo Higashi Tokushukai Hospital), Mikihiro Fujiya (Asahikawa Medical University), Takayuki Matsumoto (Iwate Medical University), Hirotake Sakuraba (Hirosaki University), Hironori Yamamoto (Jichi Medical University), Hideyuki Hiraishi (Dokkyo Medical University), Yasuharu Yakabi (Saitama Medical University), Ryota Hokari (Natinal Defense Medical College), Toshihede Ohmori (Ohmori Toshihide Gastro-intestinal Clinic), Kiyonori Kobayashi (Kitasato University), Reiko Kunisaki (Yokohama City University Medical Center), Takanori Kanai (Keio University), Mamoru Watanabe (Tokyo Medical and Dental University), Tomoo Nakagawa (Chiba University), Toshifumi Ohkusa (The Jikei University Kashiwa Hospital), Katsutoshi Tokushige (Tokyo Women's Medical University), Yasuo Suzuki (Toho University Sakura Medical Center), Toshifumi Hibi (Kitasato University Kitasato Institute Hospital), Tsuneo Fukushima (Matsushima Clinic), Atsushi Yoshida (Ofuna Chuo Hospital), Takayuki Yamamoto (Yokkaichi Hazu Medical Center), Akihiko Ohta (Ieda Hospital), Katsuhiko Nakai (Matsuda Hospital), Koichiro Matsuda (Toyama Prefectural Central Hospital), Tadashi Yokoyama (Yokoyama Hospital, Yokoyama IBD Clinic), Noriko Kamata (Osaka City University), Shiro Nakamura (Hyogo College of Medicine), Kazuhide Higuchi (Osaka Medical College), Hideki Iijima (Osaka University), Fumiko Minami (Daiwa Hospital), Minoru Matsuura (Kyoto University), Akira Andoh (Shiga University), Tomoyuki Tsujikawa (Higashi-Ohmi Medical Center), Yuji Naito (Kyoto Prefectural University of Medicine), Kenji Watanabe (Osaka City General Hospital), Akiko Shiotani (Kawasaki Medical School), Sakiko Hiraoka (Okayama University), Shinji Tanaka (Hiroshima University), Koichi Kurahara (Matsuyama Red Cross Hospital), Kazuhiro Matsueda (Kurashiki Central Hospital), Toshiyuki Matsui (Fukuoka University Chikushi Hospital), Ryuichi Iwakiri (Saga University).

NOTES

FINANCIAL SUPPORT: This work was funded by EA Pharma Co., Ltd. and undertaken by the Japanese Society for Inflammatory Bowel Disease.

CONFLICT OF INTEREST: This work was funded by EA Pharma Co., Ltd.

AUTHOR CONTRIBUTION: Study concept and design: Tadakazu Hisamatsu, Reiko Kunisaki, Shiro Nakamura, Tomoyuki Tsujikawa, Fumihito Hirai, Hiroshi Nakase, Kenji Watanabe, Kaoru Yokoyama, Masakazu Nagahori

Acquisition of data: Tadakazu Hisamatsu, Reiko Kunisaki, Hideaki Kimura, Shiro Nakamura, Fumihito Hirai, Kenji Watanabe, Makoto Naganuma, Takanori Kanai, Akihiro Yamada, Yasuo Suzuki, Noriko Kamata, Tadashi Yokoyama, Shinji Tanaka, Shingo Kato, Shigeki Bamba, Akira Andoh, Yuji Naito, Takuya Inoue, Shuhei Hosomi, Masaki Iimuro, Akira Harada, Takahiro Beppu

Analysis and interpretation of data: Tadakazu Hisamatsu, Reiko Kunisaki, Shiro Nakamura, Tomoyuki Tsujikawa, Fumihito Hirai, Hiroshi Nakase, Kenji Watanabe, Kaoru Yokoyama, Masakazu Nagahori, Akira Andoh

Drafting of the manuscript: Tadakazu Hisamatsu, Toshifumi Hibi

Critical revision of the manuscript for important intellectual content: Yasuo Suzuki, Mamoru Watanabe, Toshifumi Hibi

Statistical analysis: Hirofumi Michimae

Study supervision: Yasuo Suzuki, Mamoru Watanabe, Toshifumi Hibi

SUPPLEMENTARY MATERIALS

Supplementary Fig. 1

Protocol design. IFX (10 mg/kg) was infused intravenously every 8 weeks until week 56 or the end of the study (discontinuation). The dosage of ED (900–1200 kcal/day), determined by the examining physician at the time of main registration, was administered daily until week 56. After obtaining informed consent from the patient, the preliminary registration was carried out. At 5 to 8 weeks after the last IFX administration, and after confirming eligibility, the patients were enrolled and observed until week 56. IFX, infliximab; ED, elemental diet.

ir-16-494-s001.pdf

Supplementary Fig. 2

Patient flow diagram. IFX, infliximab; ED, elemental diet; FAS, full analysis set; PPS, per-protocol set.

ir-16-494-s002.pdf

Supplementary Table 1

Adverse Events

ir-16-494-s003.pdf

REFERENCES

1. Chan HC, Ng SC. Emerging biologics in inflammatory bowel disease. J Gastroenterol 2017;52:141–150.PMID: 27832357.Article PubMed PDF
2. Akobeng AK, Thomas AG. Enteral nutrition for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2007;(3): CD005984. PMID: 10.1002/14651858.CD005984.pub2. PMID: 17636816.Article PubMed
3. Yamamoto T, Nakahigashi M, Umegae S, Matsumoto K. Enteral nutrition for the maintenance of remission in Crohn's disease: a systematic review. Eur J Gastroenterol Hepatol 2010;22:1–8.PMID: 19707151.Article PubMed
4. Tsertsvadze A, Gurung T, Court R, Clarke A, Sutcliffe P. Clinical effectiveness and cost-effectiveness of elemental nutrition for the maintenance of remission in Crohn's disease: a systematic review and meta-analysis. Health Technol Assess 2015;19:1–138.Article PDF
5. Hirai F, Ishihara H, Yada S, et al. Effectiveness of concomitant enteral nutrition therapy and infliximab for maintenance treatment of Crohn's disease in adults. Dig Dis Sci 2013;58:1329–1334.PMID: 22926500.Article PubMed
6. Kamata N, Oshitani N, Watanabe K, et al. Efficacy of concomitant elemental diet therapy in scheduled infliximab therapy in patients with Crohn's disease to prevent loss of response. Dig Dis Sci 2015;60:1382–1388.PMID: 25532505.Article PubMed
7. Sazuka S, Katsuno T, Nakagawa T, et al. Concomitant use of enteral nutrition therapy is associated with sustained response to infliximab in patients with Crohn's disease. Eur J Clin Nutr 2012;66:1219–1223.PMID: 23010687.Article PubMed PDF
8. Sugita N, Watanabe K, Kamata N, et al. Efficacy of a concomitant elemental diet to reduce the loss of response to adalimumab in patients with intractable Crohn's disease. J Gastroenterol Hepatol 2018;33:631–637.PMID: 28857255.Article PubMed
9. Nguyen DL, Palmer LB, Nguyen ET, McClave SA, Martindale RG, Bechtold ML. Specialized enteral nutrition therapy in Crohn's disease patients on maintenance infliximab therapy: a meta-analysis. Therap Adv Gastroenterol 2015;8:168–175.Article PubMed PMC
10. Yamamoto T, Nakahigashi M, Umegae S, Matsumoto K. Prospective clinical trial: enteral nutrition during maintenance infliximab in Crohn's disease. J Gastroenterol 2010;45:24–29.PMID: 19798465.Article PubMed

Fig. 1

Percentage of patients with a decrease in CDAI from weeks 8 to 56. (A) The percentage of patients who satisfied the ΔCDAI of ≥50 from weeks 8 to 56 of treatment is shown. Proportions of patients were compared between the groups by Fisher's exact test. Statistical analyses were performed at a two-sided significance level of 0.05. (B) The percentage of patients who achieved clinical remission, as indicated by a CDAI of <150, from weeks 8 to 56 of treatment is shown. Proportions of patients were compared between the groups by Fisher's exact test. Statistical analyses were performed at a two-sided significance level of 0.05. ^aSignificant difference. ED, elemental diet; IFX, infliximab.

Fig. 2

Cumulative rate of successful completion of the scheduled maintenance treatment with IFX infusion at 10 mg/kg every 8 weeks until week 56. (A) The scheduled maintenance treatment continuation rate curve was estimated by the Kaplan-Meier method for each group, and the groups were compared by the generalized Wilcoxon test (per-protocol set). (B) The scheduled maintenance treatment continuation rate curve was estimated by the Kaplan-Meier method for each group, and the groups were compared by the generalized Wilcoxon test (full analysis set). IFX, infliximab; ED, elemental diet.

Table 1

Baseline Characteristics

	IFX mono group (n=6)	ED+IFX group (n=14)	P-value
Demographics
Sex (male/female)	5/1	11/3	1.0000
Age (yr)	35.20±10.11	34.80±8.81	0.9202
BMI (kg/m²)	21.40±4.54	21.00±4.32	0.9044
CDAI score	210.70±17.47	211.00±60.78	0.1256
Disease duration	9.24±7.23	11.13±9.04	0.9680
Disease location			1.0000
Ileitis (L1)	1 (16.7)	3 (21.4)
Ileocolitis (L2)	5 (83.3)	11 (78.6)
Perianal lesion			1.0000
Yes	2 (33.3)	4 (28.6)
No	4 (66.7)	10 (71.4)
Previous surgical resections			1.0000
0	3 (50.0)	6 (42.9)
≥1	3 (50.0)	8 (57.1)
Current smoking	1 (16.7)	2 (14.3)	1.0000
Medication at entry
Immunomodulator	2 (33.3)	4 (28.6)	1.0000
Steroid use	0	0	-
5-ASA	5 (83.3)	12 (85.7)	1.0000
Concomitant medication
Immunomodulator	2 (33.3)	5 (35.7)	1.0000
Steroid use	1 (16.7)	0	0.3000
5-ASA	5 (83.3)	12 (85.7)	1.0000
CRP (mg/dL)	0.34±0.26	0.74±0.81	0.5466
Serum albumin (g/dL)	3.88±0.32	3.91±0.63	0.4268

For calculation of the P-value, Wilcoxon's exact test was used for continuous values and Fisher exact test was used for categorical values. Statistical analyses were performed at a significance level of 0.05 (two-sided).

IFX, infliximab; ED, elemental diet; 5-ASA, 5-aminosalicylic acid.

Figure & Data

REFERENCES

Citations

Citations to this article as recorded by

Prospective study of an adalimumab combined with partial enteral nutrition in the induction period of Crohn’s disease
Sisi Zhou, Zeyu Huang, Wenjing Hou, Yiting Lin, Jing Yu
Inflammation Research.2024; 73(2): 199. CrossRef
Role of diet in prevention versus treatment of Crohn’s disease and ulcerative colitis
Emma P Halmos, Lihi Godny, Julie Vanderstappen, Chen Sarbagili-Shabat, Vaios Svolos
Frontline Gastroenterology.2024; : flgastro-2023-102417. CrossRef
Immunoregulatory Effects of Elemental Diet and Its Ingredient, Tryptophan, via Activation of the Aryl Hydrocarbon Receptor in Mice
Atsuhito Kubota, Shungo Imai, Ryoichi Aoyagi, Wataru Murase, Masaru Terasaki, Mitsuru Sugawara, Yoh Takekuma, Hiroyuki Kojima
International Journal of Molecular Sciences.2024; 25(6): 3448. CrossRef
Real-world evidence of combined treatment of biologics and exclusive enteral nutrition in patients with ileum-dominant Crohn's disease: A multicenter study
Wei Wang, Anning Yin, Jing Wang, Jiao Li, Jingyun Cheng, Jian Kang, Yaqing Xu, Yueyue Lu, Yuanping Yang, Juan Su, Qian Zhou, Ya Liu, Zhishun Tang, Haixia Ren, Weiwei Li, Weiguo Dong, Baoping Yu, Ping An
Clinical Nutrition.2024; 43(6): 1291. CrossRef
It’s Time to Change Tack in IBD Treatment
Marcel A. Behr, Ildiko Mehes, Charles N. Bernstein
Gastroenterology.2024;[Epub] CrossRef
"Out of the box� new therapeutic strategies for Crohn�s disease: moving beyond biologics
Ignacio Catalán-Serra, Pret Ricanek, Tore Grimstad
Revista Española de Enfermedades Digestivas.2022;[Epub] CrossRef
Nutritional Therapy Strategies in Pediatric Crohn’s Disease
Charlotte M. Verburgt, Mohammed Ghiboub, Marc A. Benninga, Wouter J. de Jonge, Johan E. Van Limbergen
Nutrients.2021; 13(1): 212. CrossRef
Evidence-based clinical practice guidelines for inflammatory bowel disease 2020
Hiroshi Nakase, Motoi Uchino, Shinichiro Shinzaki, Minoru Matsuura, Katsuyoshi Matsuoka, Taku Kobayashi, Masayuki Saruta, Fumihito Hirai, Keisuke Hata, Sakiko Hiraoka, Motohiro Esaki, Ken Sugimoto, Toshimitsu Fuji, Kenji Watanabe, Shiro Nakamura, Nagamu I
Journal of Gastroenterology.2021; 56(6): 489. CrossRef
Diet and nutrition in the management of inflammatory bowel disease
Pabitra Sahu, Saurabh Kedia, Vineet Ahuja, Rakesh K. Tandon
Indian Journal of Gastroenterology.2021; 40(3): 253. CrossRef
Nutritional Aspects of Pediatric Gastrointestinal Diseases
Teresa Di Chio, Christiane Sokollik, Diego G. Peroni, Lara Hart, Giacomo Simonetti, Franziska Righini-Grunder, Osvaldo Borrelli
Nutrients.2021; 13(6): 2109. CrossRef
Efficacy and tolerability of exclusive enteral nutrition in adult patients with complicated Crohn’s disease
Sanchit Sharma, Arti Gupta, Saurabh Kedia, Samagra Agarwal, Namrata Singh, Sandeep Goyal, Saransh Jain, Vipin Gupta, Pabitra Sahu, Sudheer Kumar Vuyyuru, Bhaskar Kante, Raju Sharma, Rajesh Panwar, Peush Sahni, Govind Makharia, Vineet Ahuja
Intestinal Research.2021; 19(3): 291. CrossRef
Nutritional Therapies and Their Influence on the Intestinal Microbiome in Pediatric Inflammatory Bowel Disease
Lara Hart, Charlotte M. Verburgt, Eytan Wine, Mary Zachos, Alisha Poppen, Mallory Chavannes, Johan Van Limbergen, Nikhil Pai
Nutrients.2021; 14(1): 4. CrossRef
Efficacy of enteral nutrition in patients with Crohn’s disease on maintenance anti-TNF-alpha antibody therapy: a meta-analysis
Fumihito Hirai, Teruyuki Takeda, Yasumichi Takada, Masahiro Kishi, Tsuyoshi Beppu, Noritaka Takatsu, Masaki Miyaoka, Takashi Hisabe, Kenshi Yao, Tosiharu Ueki
Journal of Gastroenterology.2020; 55(2): 133. CrossRef
Inflammatory Bowel Disease in Japan-Is It Similar to or Different from Westerns?-
Shinji Okabayashi, Taku Kobayashi, Toshifumi Hibi
Journal of the Anus, Rectum and Colon.2020; 4(1): 1. CrossRef
Exclusive enteral nutrition for induction of remission in anti-tumor necrosis factor refractory adult Crohn’s disease: the Indian experience
Ajit Sood, Arshdeep Singh, Ritu Sudhakar, Vandana Midha, Ramit Mahajan, Varun Mehta, Yogesh Kumar Gupta, Kirandeep Kaur
Intestinal Research.2020; 18(2): 184. CrossRef
Enteral nutrition in the biologic era: learn from yesterday, live for today, hope for tomorrow
Tadakazu Hisamatsu
Intestinal Research.2020; 18(2): 139. CrossRef
Half-Elemental Diet Shifts the Human Intestinal Bacterial Compositions and Metabolites: A Pilot Study with Healthy Individuals
Jun Miyoshi, Daisuke Saito, Mio Nakamura, Miki Miura, Tatsuya Mitsui, Toru Kudo, Shinnosuke Murakami, Minoru Matsuura, Tadakazu Hisamatsu
Gastroenterology Research and Practice.2020; 2020: 1. CrossRef
Fool me once… treatment exposure to achieve remission in pediatric IBD
Johan E. Van Limbergen, Bart G. P. Koot, J. Peter de Winter
European Journal of Pediatrics.2020; 179(12): 1921. CrossRef
Bases for the Adequate Development of Nutritional Recommendations for Patients with Inflammatory Bowel Disease
Esteban Sáez-González, Beatriz Mateos, Pedro López-Muñoz, Marisa Iborra, Inés Moret, Pilar Nos, Belén Beltrán
Nutrients.2019; 11(5): 1062. CrossRef

PubReader
ePub Link

Cite

CITE: export Copy Download Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

Effect of elemental diet combined with infliximab dose escalation in patients with Crohn's disease with loss of response to infliximab: CERISIER trial

Intest Res. 2018;16(3):494-498. Published online July 27, 2018

DOI: https://doi.org/10.5217/ir.2018.16.3.494

XML Download

Figure

Effect of elemental diet combined with infliximab dose escalation in patients with Crohn's disease with loss of response to infliximab: CERISIER trial

Fig. 1 Percentage of patients with a decrease in CDAI from weeks 8 to 56. (A) The percentage of patients who satisfied the ΔCDAI of ≥50 from weeks 8 to 56 of treatment is shown. Proportions of patients were compared between the groups by Fisher's exact test. Statistical analyses were performed at a two-sided significance level of 0.05. (B) The percentage of patients who achieved clinical remission, as indicated by a CDAI of <150, from weeks 8 to 56 of treatment is shown. Proportions of patients were compared between the groups by Fisher's exact test. Statistical analyses were performed at a two-sided significance level of 0.05. aSignificant difference. ED, elemental diet; IFX, infliximab.

Fig. 2 Cumulative rate of successful completion of the scheduled maintenance treatment with IFX infusion at 10 mg/kg every 8 weeks until week 56. (A) The scheduled maintenance treatment continuation rate curve was estimated by the Kaplan-Meier method for each group, and the groups were compared by the generalized Wilcoxon test (per-protocol set). (B) The scheduled maintenance treatment continuation rate curve was estimated by the Kaplan-Meier method for each group, and the groups were compared by the generalized Wilcoxon test (full analysis set). IFX, infliximab; ED, elemental diet.

Fig. 1

Fig. 2

Effect of elemental diet combined with infliximab dose escalation in patients with Crohn's disease with loss of response to infliximab: CERISIER trial

Table 1

Baseline Characteristics

	IFX mono group (n=6)	ED+IFX group (n=14)	P-value
Demographics
Sex (male/female)	5/1	11/3	1.0000
Age (yr)	35.20±10.11	34.80±8.81	0.9202
BMI (kg/m²)	21.40±4.54	21.00±4.32	0.9044
CDAI score	210.70±17.47	211.00±60.78	0.1256
Disease duration	9.24±7.23	11.13±9.04	0.9680
Disease location			1.0000
Ileitis (L1)	1 (16.7)	3 (21.4)
Ileocolitis (L2)	5 (83.3)	11 (78.6)
Perianal lesion			1.0000
Yes	2 (33.3)	4 (28.6)
No	4 (66.7)	10 (71.4)
Previous surgical resections			1.0000
0	3 (50.0)	6 (42.9)
≥1	3 (50.0)	8 (57.1)
Current smoking	1 (16.7)	2 (14.3)	1.0000
Medication at entry
Immunomodulator	2 (33.3)	4 (28.6)	1.0000
Steroid use	0	0	-
5-ASA	5 (83.3)	12 (85.7)	1.0000
Concomitant medication
Immunomodulator	2 (33.3)	5 (35.7)	1.0000
Steroid use	1 (16.7)	0	0.3000
5-ASA	5 (83.3)	12 (85.7)	1.0000
CRP (mg/dL)	0.34±0.26	0.74±0.81	0.5466
Serum albumin (g/dL)	3.88±0.32	3.91±0.63	0.4268

IFX, infliximab; ED, elemental diet; 5-ASA, 5-aminosalicylic acid.

Table 1 Baseline Characteristics

IFX, infliximab; ED, elemental diet; 5-ASA, 5-aminosalicylic acid.