Introduction

Dose escalation (DE) of intravenous infliximab is an option for inflammatory bowel disease (IBD) patients who lose response after induction therapy^{1, 2}. DE of subcutaneous (SC) infliximab from 120 mg to 240 mg every 2 weeks (Q2W) showed restoring efficacy in the 54-week LIBERTY-UC and LIBERTY-CD studies, and safety profiles were generally comparable between patients with or without DE³. Both two studies included an extension phase through Week (W) 102, and we present post-hoc long-term efficacy and safety results of DE in patients who treated in extension phase in two studies.

Aims & Methods

Patients with moderately to severely active UC and CD were treated with 3 doses of infliximab IV 5mg/kg as induction therapy (Weeks 0, 2 and 6). Clinical responders at W10 were randomized (2:1) to receive either CT-P13 SC 120 mg or placebo Q2W as maintenance therapy up to W54. Patients who, in the opinion of the investigator, would benefit from continued treatment entered open-label extension study from W56 to W102 and received CT-P13 SC 120 mg regardless of previously assigned arm. From W22, the patients who met loss of response criteria were permitted to escalate the dose to CT-P13 SC 240 mg Q2W through W102 for both arms. The results from CT-P13 SC arm are analyzed.

Results

A total of 237 and 180 patients who were randomly assigned to CT-P13 SC 120 mg arm and treated in extension phase in UC and CD study, each. Among them, DE from CT-P13 SC 120 mg to CT-P13 SC 240 mg prior to W102 was more common in UC than CD (30.0% [71/237] vs 20.6% [37/180]). Patients showed improvement in terms of clinical remission at W102 (both CD and UC) or endoscopic response at W102 (CD) after DE. Also, patients showed improvement in other efficacy endpoints after DE (Table 1). Compared to the first DE visit, patients who escalated the dose had a statistically significant reduction of more than half in mean modified Mayo score in UC (5.9 vs 2.1, P<0.0001) and mean CDAI score in CD (270.58 vs 76.31, P<0.0001) at W102.
The incidence rate of treatment-emergent adverse events (TEAEs) in the maintenance and extension phase of both studies was comparable between patients with and without DE (In UC, 84.7% [61/72] vs 78.1% [132/169], In CD, 86.8% [33/38] vs 79.7% [118/148]). Among these, TEAEs of infection were as follows; In UC, 40.3% (29/72) vs 43.2% (73/169), In CD, 55.3% (21/38) vs 42.6% (63/148). The incidence rate of treatment-emergent serious adverse events in the maintenance and extension phase of both studies was also comparable between patients with and without DE (In UC, 12.5% [9/72] vs 10.1% [17/169], In CD, 13.2% [5/38] vs 10.8% [16/148]).

Conclusion

DE of CT-P13 SC from 120 mg to 240 mg Q2W following IV induction in patients who initially respond but subsequently lose response, shows clinical efficacy over an extended observation period of 102 weeks. Safety profiles were generally comparable between patients with or without DE, and no new safety concerns were found after DE as well in long term treatment.

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 S. Danese et al. MP362 Subcutaneous infliximab (CT-P13 SC) dose escalation as an option for managing the loss of response in inflammatory bowel disease: post hoc analysis of LIBERTY-UC study and LIBERTY-CD study. Gastroenterology. Volume 166, Issue 3, Supplement, 2024, Page S13

Disclosure

• S. Schreiber: Consultancy and personal fees from AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, Falk, Ferring, Fresenius, Gilead, HIKMA, IMAB, Janssen, MSD, Morphic, Pfizer, Protagonist, Provention Bio, Sandoz, Takeda, and Theravance.
• J.F. Colombel: 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. Sandborn: Consulting fees from Alimentiv, Shoreline Biosciences; Stock or stock options from Prometheus Biosciences, Prometheus Laboratories, Ventyx Biosciences, Mirador Therapeutics; Employee at Ventyx Biosciences, Mirador Therapeutics; Board of Directors at Prometheus Laboratories.
• B.E. Sands: Consultant or received speaker’s fees from AbbVie, Abivax, Adiso Therapeutics, AgomAb, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion, ClostraBio, Connect Biopharm, Cytoki Pharma, Eli Lilly and Company, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead Sciences, 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.
• 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.
• ​S.J. Lee, S.H. Kim, ​Y.J. Bae, S.H. Lee, S.G. Lee, J.H. Lee, J.M. Kim, G.H. Park, ​J.M. Lee, J.H. Lee are Employee of Celltrion, Inc.

Introduction

Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that potently neutralizes IL-23 and binds to CD64, a receptor on cells that produce IL-23. In the QUASAR studies, GUS intravenous (IV) induction and subcutaneous (SC) maintenance demonstrated symptomatic, endoscopic, and histologic efficacy through 2 years.^1,2 Here, we describe maintenance of endoscopic and histologic efficacy in the long-term extension (LTE).

Aims & Methods

At maintenance week (W) 0, GUS IV induction responders were randomized 1:1:1 to GUS 100 mg SC every 8 weeks (q8w), GUS 200 mg SC q4w or placebo (GUS withdrawal). Participants (pts) completing the W44 visit could enter the LTE and continue the treatment regimen they were receiving at W44. Placebo pts discontinued after study unblinding. Efficacy data for randomized pts who continued to receive their GUS regimen assigned at W0 in the LTE were analyzed using 2 methods: 1) nonresponder imputation (NRI) accounting for pts with treatment failure or missing data, and 2) “as observed.”

Results

Overall, 303 randomized pts (155 for 100 mg q8w and 148 for 200 mg q4w) continued their GUS treatment assigned at W0 in the LTE. Of pts who achieved endoscopic improvement at W44, 87.2% of GUS 100 mg q8w pts and 80.2% GUS 200 mg q4w pts maintained endoscopic improvement through W92 (NRI analysis; Table). Of pts who achieved histologic improvement at W44, 77.9% and 75.2%, respectively, maintained histologic improvement at W92. Of pts who achieved histo-endoscopic mucosal improvement (HEMI) at W44, 73.5% and 75.5%, respectively, maintained HEMI through W92. Of pts who were in histologic remission at W44, 71.2% maintained histologic remission at W92 in both GUS groups. Results of the as-observed analysis were consistent with the NRI analysis; the dropout rate was low among GUS-treated pts in the LTE. Proportions of pts who maintained endoscopic and histologic outcomes from W0 to W92 are presented in the Table.

Conclusion

High rates of long-term sustained endoscopic and histologic endpoints were observed at W92 of the LTE with both GUS dose regimens.

References

1. Rubin DT, et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2025;405(10472):33-49.
2. Lichtenstein GR, et al. Efficacy and safety of guselkumab for ulcerative colitis through week 92 of the QUASAR long-term extension study. Presented at: Digestive Disease Week (DDW); May 4–6, 2025; San Diego, CA.

Disclosure

Study support: Johnson & Johnson.
TH: AbbVie, Bristol Myers Squibb, Daiichi-Sankyo, EA Pharma Co, Ltd., JIMRO, Eli Lilly, Gilead Sciences, Johnson & Johnson, Kissei Pharmaceutical Co, Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc, Takeda Pharmaceutical Co., Ltd.
JP: AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Johnson & Johnson, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, Wasserman.
FM: AbbVie, Arena, Celltrion, Eli Lilly and Company, Ferring, Fresenius, Galapagos, GlaxoSmithKline, Johnson & Johnson, Merck, Pfizer, Prometheus Biosciences, Roche, Sandoz, Tillots, Takeda, Teva.
GRL: AbbVie, American College of Gastroenterology, CellCeutrix, Celgene, Clinical Advances in Gastroenterology, Ferring, Gastroenterology and Hepatology [Gastro-Hep Communications], Gilead, Johnson & Johnson, Orthobiotech, Eli Lilly, Luitpold / American Regent, Merck, McMahon Publishing, Pfizer, Prometheus, Romark, Salix/ Valeant, Shire, SLACK, Springer, Takeda, UCB, Up-To-Date, Vindico, Virgo.
JRA: Abbvie, Bristol Myer Squibb, Ferring, Finch, Iterative Scopes, Johnson & Johnson, Merck, Pfizer, Roivant, Seres Therapeutics, Roivant Adiso.
BB: AbbVie, Alimentiv, Allergan, Amgen, AMT, Bausch Health, Bristol Myers Squibb, Business Intelligence, Celgene, Celltrion, Eupraxia Fresenius Kabi, Ferring, Genentech/Roche, Gilead, Iterative Scopes, GlaxoSmithKline, Jamp, Johnson & Johnson, Merck, Microbiome Insights, Mylan, Novartis, Organon, Pendopharm, Pfizer, Protagonist, Qu Biologic, Sandoz, Takeda, Viatris.
WA: AbbVie, Amgen, BMS, Dynacare, Eli-Lilly, Johnson & Johnson, Merck, Novartis, Pfizer, Prometheus, Sandoz, Sanofi, Takeda, Theradiag.
MAS: AbbVie, Bristol-Myers Squibb, Falk, Galapagos, Janssen, Lilly, MSD, Pfizer, Samsung Bioepis, Sandoz, Sanofi, STADA, Takeda, Tillotts.
BDY: AbbVie Korea, BMS Pharmaceutical Korea Ltd., Celltrion, Chong Kun Dang Pharm, CJ Red BIO, Cornerstones Health, Curacle, Daewoong Pharm, Dong-A ST, Eisai Korea, Eli Lilly and Company Korea, Ferring Korea, Imscout, IQVIA, Johnson & Johnson, Johnson & Johnson Korea, JEIL PHARMACEUTICAL CO., Kangstem Biotech, Korea Otsuka Pharm, Korea United Pharm, Medtronic Korea, NanoEntek, ORGANOIDSCIENCES LTD, Pfizer Korea, Samsung Bioepis, Takeda, Takeda Korea, Yuhan.
SY, MG, NS, DP, YM, HZ: Johnson & Johnson.
AD: Abivax, AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, CED Service GmbH, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Gilead, High5MD, Johnson & Johnson, Lilly, Materia Prima, MedToday, MSD, Pfizer, Pharmacosmos, Roche, Sandoz, Stada, Takeda, Thieme, Tillotts, UniMed Verlag, Vifor Pharma.
DTR: Abbvie, Altrubio, Apex, Avalo Therapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Johnson & Johnson, Lilly, Pfizer, Samsung Neurologica, Takeda.
BES: AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Celltrion, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Johnson & Johnson, Kaleido, Kallyope, Lilly, Merck, Microba, Mirador Therapeutics, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Sorriso Pharmaceuticals, Spyre Therapeutics, Sun Pharma, Surrozen, Takeda, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences, and Vividion Therapeutics.

Introduction

The PROTDILAT study (Loras et al. Lancet Gastroenterol Hepatol. 2022) at 1-year follow-up showed greater efficacy of EBD vs SEMS for the treatment of short strictures in CD. However, long term efficacy of endoscopic treatmetn is still debated, especially for EDB.

Aims & Methods

Aims: To assess the long-term evolution of patients included in PROTDILAT study. 1). Percentage of patients free of surgery; 2) Factors related to surgery; 3) Need for endoscopic retreatments; 4) Effectiveness related to the type of initial endoscopic treatment (EBD vs SEMS); 5) Complications related to endoscopic or surgical treatment.
Methods: Retrospective study based on PROTDILAT trial database (patients with CD, obstructive symptoms, with stenosis <10cm). Data on medical, endoscopic and surgical treatment and smoking habits were collected. The effectiveness of endoscopic treatment is defined by the percentage of patients free of surgery and endoscopic retreatment at the end of follow-up.

Results

Information available on 80/80 patients (39 SEMS, 41 EBD), 39 women, age (median): 45y (IQR: 38-55); median stricture length 3.4cm (IQR: 2-5.5), 42.5% being anastomotic. Thirty-one percent (25/80) of patients required surgical resection [(median time to surgery 30.61 months (6.35-55.24)). Factors associated to surgery: non-intensification of therapy (HR 0.26 (0.10-0.68)), treatment with EBD exclusively (HR 0.22 (0.08-0.58)) (with respect to treatment with EBD + SEMS) and number of stents (HR 2.31 (1.10-4.84)). Of the 55 patients free of surgery, during the entire follow-up (median 84 months (74.7-84.0)), a median of 2 endoscopic procedures (1-3) were performed: EBD in 45 cases (80.0%) and SEMS in 26 cases (46%). Thirty-eight-point seventy-five percent (31/80 patients) did not require neither surgery nor endoscopic retreatment during the follow-up. The long-term effectiveness of endoscopic treatment was 45% for SEMS and 57.6% for EBD (p=0.374). The complications related to endoscopic or surgical treatment were 8.75% (7/80) versus 36% (9/25) respectively (p=0.002). As for the severity of complications (AGREE/CLAVIEN-DINDO ≥ III), it was observed that surgical treatment presented more severe complications than endoscopic treatment (Endoscopic vs surgical treatment: 38% (3/8) vs 84% (10/12), p=0.011).

Conclusion

Endoscopic treatment (predominantly EBD) avoids surgery in most cases, requiring a low number of endoscopic treatments in the long-term. Patients at higher risk for surgery are those with a greater number of endoscopic treatments that include SEMS and EBD. On the contrary, protective factors are non-intensificationof therapy and having been treated exclusively with EBD. Although there are no significant differences in the long effectiveness between SEMS and EBD, a trend for a better outcome is observed for EBD. To highlight a significant higher rate of complications observed in surgicaltreatment compared to endoscopic treatment.

References

Loras et al. Lancet Gastroenterol Hepatol. 2022

Disclosure

No conflict of Interest