Introduction

Dose escalation of IV infliximab is an option for inflammatory bowel disease (IBD) patients who lose response after induction therapy^1,2. However, as yet, there is limited data for CT-P13 subcutaneous (SC) infliximab (CT-P13 SC) dose escalation in IBD patients.

Aims & Methods

The aim of the post hoc analysis was to evaluate the efficacy, safety, and immunogenicity of treatment with CT-P13 SC dose escalation in patients who initially responded but then lost response according to the loss of response (LOR) criteria in LIBERTY-UC³ and LIBERTY-CD⁴ studies, which were conducted in parallel over 54 weeks. Patients with moderately to severely active UC and CD were treated with 3 doses of infliximab IV 5mg/kg as induction therapy. Clinical responders at Week 10 were randomized (2:1) to receive either CT-P13 SC 120 mg or placebo every 2 weeks as maintenance therapy. From Week 22, the patients who received CT-P13 SC 120 mg every 2 weeks and who met LOR criteria were permitted to escalate the dose to CT-P13 SC 240 mg (double injection [2 shots] of CT-P13 SC 120 mg) every 2 weeks.

Results

A total of 294 and 231 patients were randomized to CT-P13 SC 120mg in UC and CD study, each. Among them, dose escalation from CT-P13 SC 120 mg to CT-P13 SC 240 mg prior to Week 54 was more common in UC than CD [27.6% (81/294) vs 16.9% (39/231)]. Of dose-escalated patients, 74.1% (60/81) and 51.3% (20/39) received their first dose of CT-P13 SC 240 mg at Week 22 in the UC and CD studies, respectively.
In both UC and CD studies, patients showed improvement in terms of clinical remission [In UC, 24.7% (20/81), In CD, 53.8% (21/39)] or endoscopic response [In CD, 28.2% (11/39)] after dose escalation. Compared to the first dose escalation visits, patients who escalated the dose had almost a half, statistically significant, reduction in modified Mayo score in UC and CDAI score in CD at Week 54. (Table 1).
The incidence rate of treatment-emergent adverse events (TEAEs) in the maintenance period of both studies was comparable between patients with and without dose escalation [In UC, 72.8% (67/92) vs 65.2% (133/204), In CD, 71.1% (32/45) vs 72.5% (140/193)]. Among these, TEAEs of infection were as follows [In UC, 27.2% (25/92) vs 28.4% (58/204), In CD, 35.6% (16/45) vs 30.1% (58/193)].
In both studies, rates of anti-drug antibody (ADA) and neutralizing antibody (NAb) positive conversion up to Week 54 showed no difference in patients with and without dose escalation as follows [In UC, ADA 55.7% (49/88) and 67.3% (134/199), NAb 87.8% (43/49) and 88.1% (118/134), respectively. In CD, ADA 68.2% (30/44) and 64.4% (121/188), NAb 96.7% (29/30) and 97.5% (118/121), respectively].

Table 1. Summary of efficacy outcome in CT-P13 SC treated patients at Week 54

Conclusion

Dose escalation of CT-P13 SC from 120 mg to 240 mg every 2 weeks may be effective in restoring efficacy. Safety profiles including immunogenicity results were generally comparable between patients with or without dose escalation. No new safety concerns were found after dose escalation.

References

1 Taxonera C et al. Infliximab dose escalation as an effective strategy for managing secondary loss of response in ulcerative colitis. Digestive Diseases and Sciences 2015; 60 (10): 3075-3084
2 Cesarini M et al. Dose optimization is effective in ulcerative colitis patients losing response to infliximab: A collaborative multicentre retrospective study. Dig Liver Dis.2014; 46(2): 135-139.
3 Bruce E. Sands et al. Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for ulcerative colitis: A phase 3, randomized, placebo-controlled study: Results of the Liberty-UC Study. Journal of Crohn's and Colitis. 2023;17(Supplement_1):i623–i624
4 J.F. Colombel et al. Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn’s disease: A phase 3, randomised, placebo-controlled study (LIBERTY-CD). Journal of Crohn's and Colitis. 2023;17(Supplement_1):i161-i162

Disclosure

- S. Danese: Consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor. Reports lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda.
- J.F. Colombel: Receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda. Receiving payment for lectures from AbbVie, Amgen, Allergan, Inc. Ferring Pharmaceuticals, Shire, and Takeda. Receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech, Glaxo Smith Kline, Janssen Pharmaceuticals, Kaleido Biosciences, Imedex, Immunic, Iterative Scopes, Merck, Microbia, Novartis, PBM Capital, Pfizer, Protagonist Therapeutics, Sanofi, Takeda, TiGenix, Vifor. Hold stock options in Intestinal Biotech Development.
- S.B. Hanauer: Consultancy from AbbVie, Allergan, Amgen, Arena, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cosmos, Catalys Pacific, Covance, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Progenity, Prometheus, Receptos, Salix, Samsung Bioepis, Seres Therapeutics, Sorriso, Takeda, TLL, UCB, Vhsquared. Clinical Research for AbbVie, Allergan, Amgen, Celgene, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer, Prometheus, Receptos, Takeda, UCB. Speaker for AbbVie, Bristol Myers Squibb, Janssen, Pfizer, Takeda. Independent Data Monitoring Conference for Arena, Boehringer Ingelheim, Bristol Myers Squibb, Gossamer, Prometheus, Protagonist.
- W.J. Sandborn: Consulting fees from Abbvie, Abivax, Alfasigma, Alimentiv, Beigene, Biora (Progenity), Celltrion, Forbion, Genentech, Gossamer Biosciences, Index Pharmaceuticals, Prometheus Biosciences, Protagonist Therapeutics, Shoreline Biosciences, Vedanta Biosciences, Ventyx Biosciences, Zealand Pharma. Stock or stock options from BeiGene, Gossamer Bio, Biora (Progenity), Prometheus Biosciences, Prometheus Laboratories, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivreon Gastrosciences. Employee at Shoreline Biosciences and Ventyx Biosciences.
- B.E. Sands: Consultant/ Speaker’s fees from AbbVie, Abivax, Adiso Therapeutics, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion Healthcare, ClostraBio, Connect Biopharm, Cytoki Pharma, Eli Lilly and Company, Entera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead, Genentech, Glaxo SmithKline, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kalyope, Merck, MiroBio, Morphic Therapeutic, MRM Health, OSE Immunotherapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, RedHill Biopharma, Sun Pharma Global, Surrozen, Synlogic Operating Company, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, Viela Bio. Stock options from Ventyx Biosciences.
- S. Schreiber: Consultancy and personal fees from AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, Falk, Ferring, Fresenius, Gilead, HIKMA, IMAB, Janssen, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Sandoz, Takeda, and Theravance.
- S.J. Lee, S.H. Kim, Y. Bae, S. Lee, S.G. Lee, J.H. Lee, J.M. Kim, S. Yang, J. Lee, G. Park, J. Lee: Employee of Celltrion, Inc.

Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder from the atopic disease spectre. Despite being studied for years, the EoE-specific therapy has been approved only recently and includes budesonide orodispersible tablet (1) and IL-4R antagonist, dupilumab (2). Therefore, data on the management of the patients who do not respond to this treatment is scarce. Especially those who were diagnosed long in the past and have undergone different therapeutical approaches remain an understudied group. The aim of this project was to provide information on the treatment courses in a real-world setting over past 10 years.

Aims & Methods

This was a retrospective nation-wide project collecting data on patients with EoE in 7 Austrian centres since January 2014. The last follow-up was marked as of February 2025. Information on patients’ demographics, previous medical history, number of esophageal food impactions and different treatment lines were recorded. Due to the descriptive character of the work, no power analysis was carried out.

Results

In total, 336 patients (30.1% female) were included. Approximately one third of them (119/336) experienced an esophageal food impaction before the diagnosis was made. The most common 1st line therapy was budesonide orodispersible tablet (193/336, 57.4%), followed by proton pump inhibitors (87/336, 25.9%) and food elimination diet (20/336, 6.0%). Two hundred twenty (220/336, 65.5%) patients did not remain on the 1^st line treatment. Forty-four (44/336, 13.1%) subjects required more than 2 therapies and one person received even 7^th line medication. Biologic treatment – dupilumab – was given to forty-one (12.2%) patients. It was the first line treatment in 1 person, the others received it in the further course. These drugs were well-tolerated and 97.6% (40/41) patients remained on it until the last follow-up and reached symptomatic remission. Three patients were diagnosed more than 10 years before they received biologic treatment and 2 of them responded to it. One person discontinued due to side effects. The most common reasons for switch for dupilumab were clinical and/or histological activity (24/41, 58.5%), side effects (10/41, 24.4%) and patients’ preference (2/41, 4.9%).

Conclusion

This is the first study on different therapy courses in patients with EoE in Europe. Due to its retrospective character, no direct conclusions on the superiority of one approach upon another in case of refractoriness are possible.

References

1. Lucendo AJ, Miehlke S, Schlag C, Vieth M, von Arnim U, Molina-Infante J, et al. Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial. Gastroenterology. 2019;157(1):74-86.e15.
2. Hirano I, Dellon ES, Hamilton JD, Collins MH, Peterson K, Chehade M, et al. Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis. Gastroenterology. 2020;158(1):111-22.e10.

Disclosure

JP: travel grants from Johnson&Johnson and Tillots Pharma AG
MW: no conflicts of interest
PD: consulting and speakers fees from Falk Pharma, Sanofi, Abbvie, MSD, Takeda, Janssen, Pfizer
KS: support from: Abbvie, Astro Pharma, Takeda, Johnson&Johnson, MSD, Falk Pharma, Galapagos
TH: speaker fee from Falk
MH: no conflicts of interest
LKS: •Past/present Principal investigator für Studien gesponsort durch: SigmaTau, Sanofi , Tigenix und Falk;
•Speaker fee: MSD, AbbVie, Ferring, MerckSerono/Dr Falk, Chiesi, Novartis, Roche, Abbott, Phadia Austria/Thermo Fisher Scientific, CSL-Behring , Janssen-Cilag Pharma, Labors.at GmbH, Vertex, ENML Laborbetriebs GmbH, Johnson&Johnson
•Conference support: Mylan, Abbott, MSD, Gilead, MerckSerono/Dr Falk, Novartis, Pfizer, Janssen-Cilag Pharma, Chiesi, Shire, Abbvie, Takeda, Vertex, Astropharma
•Consultancy for: MSD, Takeda
GN: lecturing fees, consulting fees, and advisory fees from AbbVie, Merck Sharp & Dohme, Takeda, Janssen-Cilag, Pfizer, Gilead, Galapagos, Ferring, Vifor, AstroPharma, Falk, Bristol Myers Squibb, Arena Pharmaceuticals and Amgen
MT: received grant support from Albireo, Alnylam, Cymabay, Falk, Genentech, Gilead, Intercept, MSD, Takeda and UltraGenyx, honoraria for consulting from AbbVie, Albireo, Agomab, Boehringer Ingelheim, BiomX, Chemomab, Dexoligo Therapeutics, Falk, Genfit, Gilead, GSK, Hightide, Intercept, Ipsen, Jannsen, MSD, Novartis, Phenex, Pliant, Regulus, Siemens and Shire, speaker fees from Albireo, Boehringer Ingelheim, Bristol-Myers Squibb, Falk, Gilead, Intercept, Ipsen, Madrigal, Mirum and MSD , as well as travel support from AbbVie, Falk, Gilead, Jannsen and Intercept. He is also co-inventor of patents on the medical use of 24-norursodeoxycholic acid filed by the Medical University of Graz (service inventions).
WS: no conflicts of interest
HS: consulting and speakers fees from Falk Pharma, Sanofi, Medtronic
PS: consulting fees and/or speaker fees from Dr. Falk Pharma, GmbH, Takeda, Regerenon-Sanofi Pharmaceuticals, AbbVie, Janssen-Cilag, Receptos-Celgene-BMS

Introduction

Guselkumab (GUS), interleukin-23p19 subunit inhibitor, has been approved for moderately to severely active Crohn’s disease (CD) in Japan. CNTO1959CRD3003 is a Phase 3, open-label, multicenter study designed to evaluate the safety and efficacy of GUS in Japanese patients with moderately to severely active CD. We report the efficacy of GUS on small bowel lesions.

Aims & Methods

The primary objective was to evaluate safety, and the secondary objective was to evaluate the efficacy of GUS at week 48 (W48). An exploratory objective was to assess the efficacy of GUS for small bowel lesions, evaluated using retrograde balloon-assisted enteroscopy (BAE). Eligible patients in this study were patients with active ileocolonic CD or small bowel CD, as clarified by endoscopic evaluation. GUS 200 mg was administered intravenously on Weeks 0, 4, and 8 and subcutaneously every 4 weeks from week12 until W44. As optional, small bowel lesions were assessed using modified simple Endoscopic Score for Crohn’s Disease [mSES-CD], excluding stricture evaluation. The sum of the proximal ileum (10-300 cm from ileocecal valve) and terminal ileum sub-scores was defined as a partial modified SES-CD (pmSES-CD). Within patients with pmSES-CD score of 4 or more at baseline, those with a score reduction of 50% at W48 from the baseline were defined as endoscopic responder; a pmSES-CD score of less than 4 points was defined as ulcer-free, and a pmSES-CD score of 0 was defined as complete mucosal healing.

Results

A total of 38 patients were enrolled and received GUS treatment. Most participants were male (24/38; 63.2%), and the median age was 40.5 (range: 20-69) years. This group included 8 with ileal type, 9 with colonic type, and 21 with ileocolonic type. The median duration of CD was 7.97 (0.4–33.0) years. Overall, 33/38 patients (86.8%) experienced an adverse event (AE) and 3/38 (7.9%) experienced a serious AE. There were no CD-related hospitalizations or surgeries, and no new safety concerns were identified regarding GUS treatment through W48.
Among the 38 patients, 15 patients were evaluated for small bowel lesion using retrograde BAE, defined as the small bowel (SB) group. Among these, the median age was 41.0 (24-69) years, and the median duration of CD was 2.92 (0.4-16.9) years. The median pmSES-CD was 8.0 (0-14) at baseline and 5.0 (0-13) at W48. 7/15 patients (46.7%) were endoscopic responders, 4/15 patients achieved ulcer-free (26.7%), and 2/15 patients (13.3%) achieved complete mucosal healing at W48 (Table.1). Three participants (20.0%) showed improvement of 5 points or more in the lesions of the proximal ileum as measured by pmSES-CD. Two of three ileal type patients achieved ulcer-free at W48. No AE of strictures were reported through W48.

Table 1. Result of efficacy of guselkumab treatment on small bowel lesions.

Conclusion

Overall, this study showed that GUS is well-tolerated and effective for treating patients with moderately to severely active CD, and the results also suggested the effectiveness of GUS in small bowel lesions.

Disclosure

TH: Grant: EA pharma Co. Ltd., AbbVie GK, Pfizer Inc., Mitsubishi Tanabe Pharma Corporation, Kyorin Pharmaceutical Co. Ltd., JIMRO Co.Ltd, Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Zeria Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Kissei Pharmaceutical, Boston Scientific
Consulting fees: EA pharma Co. Ltd.,AbbVie GK,Pfizer Inc.,Mitsubishi Tanabe Pharma Corporation,Takeda Pharmaceutical Co. Ltd.,Gilead Sciences, Inc.,Eli Lilly and Co.,Janssen Pharmaceutical K.K.,Bristol Myers Squibb,Abivax
Payment or honoraria for lectures, presentations, speakers;
EA pharma Co. Ltd.,AbbVie GK,Pfizer Inc.,Mitsubishi Tanabe Pharma Corporation,Kyorin Pharmaceutical Co. Ltd.,JIMRO Co.Ltd,Mochida Pharmaceutical Co., Ltd.,Takeda Pharmaceutical Co. Ltd.,Zeria Pharmaceutical Co. Ltd.,Nippon Kayaku Co. Ltd.,Janssen Pharmaceutical K.K.
TK: Grant: Abbie GK, Alfresa Pharma Corporation, EA Pharma, Gilead Sciences, Inc. Nippon Kayaku Co., Ltd., Eli Lilly Japan K.K., Mochida Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Pfizer Japan Inc., Sekisui Medical, Takeda Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation, Zeria Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Consulting fees :Takeda Pharmaceutical Co., Ltd., Alfresa Pharma Corporation, Zeria Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Abbie GK, Pfizer Japan Inc., Janssen Pharmaceutical K.K., JIMRO Co., Ltd., Galapagos, Takeda Pharmaceutical Co., Ltd., Expert testimony : EA Pharma Co., Ltd., KISSEI Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd., Pfizer Japan Inc., Nippon Kayaku Co., Ltd., Alfresa Pharma Corporation, Abbie GK, Mochida Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K.
KW: Consulting fees: EA Pharma Co., Ltd., Payment or honoraria for lectures, presentations, speakers: Takeda Pharmaceutical Co., Ltd., AbbVie Japan Co., Ltd., EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., JIMRO Co., Ltd.
Participation on a Data Safety Monitoring Board or Advisory Board: Takeda Pharmaceutical Co., Ltd., Leadership or fiduciary role in other board, society, committee : Japanese Society of Gastroenterology, Japanese Society of Gastrointestinal Endoscopy, Japanese Gastroenterological Association, Japan Society of Coloproctology, Japanese Society of Mucosal Immunology, Japan Society for Inflammatory Bowel Disease, Japanese Society of Small Intestinal Disease, Japanese Association for Capsule Endoscopy, Research group of intractable IBD, the Ministry of Health, Labor and Welfare in Japan
KO All support for the present manuscript : J&J Innovative Medicine, Payment or honoraria for lectures, presentations, speakers: AbbVie Inc, EA Pharma Co.,Ltd, Janssen Pharmaceutical, KYORIN Pharmaceutical, Mitsubishi Tanabe Pharma, MOCHIDA PHARMACEUTICAL, Nippon Kayaku Co.,Ltd, OLYMPUS CORPORATION, Takeda Pharmaceuticals, Zeria Pharmaceutical Co., Ltd.
ME: Grant: Kyorin Pharmaceutical Co. Ltd, Payment or honoraria for lectures, presentations, speakers: AbbVie GK, Mitsubishi Tanabe Pharma, EA Pharma Co., Ltd, Janssen Pharmaceutical, Takeda Pharmaceuticals, Pfizer Japan Inc., Gilead Sciences Inc., Mochida Pharmaceutical Co. Ltd
TO: Payment or honoraria for lectures, presentations, speakers: AbbVie GK., Takeda Pharmaceutical Co. Ltd., and KISSEI Co. Ltd
NH: Expert testimony : J&J Innovative Medicine
TM: None
TS, KM, MC, HH and SY are employees of Johnson & Johnson.