Introduction

Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC) and in development for the treatment of other immune-mediated inflammatory diseases. Based on animal studies at clinically relevant doses, etrasimod may cross the placenta and cause foetal harm. This analysis describes pregnancy outcomes in patients with maternal or paternal exposure to etrasimod during its clinical development.

Aims & Methods

Reports of pregnancy or partner pregnancy during etrasimod exposure were identified from all phase 1–3 completed or ongoing open-label studies up to 31 October 2023. These studies included healthy volunteers or patients with UC, Crohn’s disease, atopic dermatitis, eosinophilic esophagitis or alopecia areata. In all studies, pregnancy was an exclusion criterion, women of childbearing age were required to use contraception and study drug was discontinued in any female patient that became pregnant. Pregnancy outcomes were categorised as healthy newborn, medical termination, foetal death, congenital malformation, spontaneous abortion or lost to follow-up.

Results

In total, 2091 unique patients were exposed to etrasimod in clinical trials; 593 (28.4%) were females of childbearing age (aged 16–44). There was a total of 14 pregnancies with exposure to etrasimod (nine maternal, five paternal). All pregnancy exposures were limited to the first trimester. Median (range) age of women with maternal etrasimod exposure was 28.0 (18–36) years. Estimated length of maternal etrasimod exposure (from last menstrual period until last etrasimod dose) ranged from 22 to 79 days. Of the nine maternal exposures, pregnancy outcomes were two healthy newborns, four medical terminations (two for unknown reasons, one due to an anembryonic gestation and one following “signs of a missed pregnancy”) and one each resulting in a congenital malformation (open [patent] foramen ovale), spontaneous abortion and loss to follow-up (Table). Of the five paternal exposures, there were two healthy newborns, two spontaneous abortions and one lost to follow-up (Table).

Conclusion

Few pregnancies have been reported in the etrasimod clinical programme, with no clear trends on the risk of maternal or paternal etrasimod exposure. Ongoing etrasimod studies and larger post-marketing registries will further inform on the safety of etrasimod during pregnancy. Women of child-bearing potential should use birth control while on etrasimod.

Disclosure

KBG has received research support from Celltrion, Galapagos, and Pfizer Inc; speakers’ honoraria and/or consulting fees from AbbVie, Celltrion, Ferring Pharmaceuticals, Immunic Therapeutics, Janssen, Novartis, Pfizer Inc, Samsung Bioepis, Takeda, and Tillotts. MC is a consultant/advisor for Gilead, Janssen, Lilly, Pfizer Inc, Takeda and Tillots; has received grant/research support from Galápagos, Janssen and Pfizer Inc; is an investigator for AbbVie, Boehringer Ingelheim Ltd., Celgene, F Hoffman La Roche, Genentech, Hospira, Janssen Cilag International LV, Janssen Cilag International NV, Millenium Pharmaceuticals, Shield, Shire and Takeda and principal investigator for AbbVie, Ferring Pharmaceuticals, Janssen, MSD and Takeda. MTA is a consultant for Janssen, Prometheus Bioscience, Takeda, Gilead, Eli Lilly, AbbVie Inc, Amgen, Arena Pharmaceuticals, Bristol Myers, Celsius, Microba Life Sciences, Pfizer, UCB Biopharma, Prometheus and Janssen Biotech Inc. YL is an advisory committee/board member for Takeda, Pfizer, Eli Lilly, Janssen, AbbVie, Celltrion, Sandoz and consultant for Takeda, Pfizer, Eli Lilly, Janssen and AbbVie. ES is a consultant for AbbVie and Janssen and has received speaker fees from Biogen, Dr. Falk Pharma, Janssen, AbbVie, Takeda, BMS, Celltrion and CED Service GmbH. AM is an employee of Pfizer Ltd and shareholder of Pfizer Inc. KL is an employee of Pfizer AG and shareholder of Pfizer Inc. JW, CCS and MD are employees and shareholders of Pfizer Inc. KW is an employee and shareholder of Pfizer Canada Inc. UM is an advisory/committee board member for Merck (DSMB) and Rana Therapeutics; consultant for Abbvie, Bristol Myers Squibb, Boeringher Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Pfizer, Protagonist, Roivant and Takeda and has received grant/research support from Leona and Harry Helmsley Trust.

Introduction

Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking drug indicated for ulcerative colitis (UC), is administered intravenously at Weeks 0, 2, and 6, then every 8 weeks (Q8W). Dose escalation to every 4 weeks (Q4W) may recapture response to treatment in ~50% of patients with inadequate response. Real-world outcomes and factors associated with VDZ dose escalation from Q8W to Q4W remain underexplored.

Aims & Methods

Adults with moderate to severe UC initiating VDZ Q8W maintenance were prospectively followed in a Canadian patient support program (2015-2023). Two cohorts were included: 1) patients escalated to Q4W during maintenance after week 14 infusion (Q8W>Q4W maintenance) and 2) patients maintained on Q8W treatment for ≥2 years without escalating (Q8W maintenance). Rates of clinical remission (partial Mayo Score [PMS]<3) were described by prior biologic experience. Associations between baseline characteristics and clinical remission 3 months after Q4W dose escalation were assessed using Wilcoxon rank sum test and Fisher’s exact test. Treatment persistence at 12 and 24 months after initiation and dose escalation were evaluated in Q8W>Q4W maintenance using Kaplan-Meier survival analysis.

Results

373 patients (68% bio-naïve) and 300 patients (72% bio-naïve) were included in the Q8W>Q4W maintenance and Q8W maintenance cohorts, respectively. Median age at treatment initiation was 47 years in Q8W>Q4W maintenance and 48 years in Q8W maintenance. Both cohorts had a median baseline PMS score of 6. In Q8W>Q4W maintenance, median disease duration before treatment initiation was 4 years and median follow-up was 19 months. In Q8W maintenance, median disease and follow-up duration were 5 years and 35 months, respectively. 14 weeks post-treatment initiation, rates of remission in Q8W>Q4W maintenance were 49% (bio-naïve) and 42% (bio-experienced), and in Q8W maintenance were 72% (bio-naïve) and 70% (bio-experienced) (Table 1). Among patients in Q8W>Q4W maintenance not in remission when dose escalating, 40% achieved clinical remission 3 months after dose escalation. These patients were older at treatment initiation (49 vs. 41 years, p=0.043) and had longer disease duration (6 vs. 3 years, p=0.029) than those who did not achieve remission. In Q8W>Q4W maintenance, 12- and 24-month treatment persistence after initiation was 83% and 48% (bio-naïve) and 79% and 51% (bio-experienced), respectively. After dose escalation, 12- and 24-month treatment persistence was 48% and 39% (bio-naïve) and 53% and 45% (bio-experienced).

Conclusion

Patients with UC who underwent VDZ Q8W>Q4W dose escalation achieved lower rates of remission than those remaining on Q8W, regardless of prior bio-experience. Age at treatment initiation and disease duration were significantly associated with remission among those who escalated to Q4W.

Disclosure

JFL: AbbVie, BMS, Janssen, Frenesius-Kabi, Pfizer, Sandoz, Takeda.
EJB: Participation in advisory boards or speaker services: Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, Eli Lilly, BMS, Grant/Research: Janssen, Abbvie, Any other investment or relationship that could be judged by a reasonable and knowledgeable participant to have the potential to influence the content of the training activity, Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, BMS.
AHS: Advisory Board Membership/Consultant: Abbvie, Amgen, BioJAMP, BMS, Celltrion, Fresenius Kabi, Janssen, McKesson, Mylan Pharmaceuticals, Organon, Pendopharm, Roche, Pfizer, Sandoz, Takeda, Viatris, Speakers’ Bureau: Abbvie, Amgen, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer, Sandoz, Takeda, Research Grants: Abbvie, Arena, Celgene/BMS, Genentech, Janssen, Roche, Takeda.
PW: Personal fees from AbbVie, Ferring, Biogen, and Janssen
MJA, AW, RW: were employees of Takeda Canada Inc. at the time of the study.
RM, JW, CP: were employees of Pentavere Research Group Inc. at the time of the study.
LPB: Consulting from AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HACPharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and Vectivbio; grants from Takeda, Fresenius Kabi, and Celltrion; and lecture fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, and Medac.
BB: Advisor/Speaker: Ferring, Janssen, Abbvie, Takeda, Pfizer, BMS, Merck, Sandoz, Organon, Lifelabs, Celltrion. Advisor: Alimentiv, Gilead, Iterative Health, AMT, Celgene, Merck, Amgen, Pendopharm, Eli Lilly, BMS, Fresenius Kabi, Mylan, Viatris, Bausch Health, Celltrion Healthcare, BioJamp Pharma, Eupraxia. Research support: Janssen, Abbvie, GSK, BMS, Amgen, Genentech, Merck. Stock Options: Qu Biologic.

Introduction

Systemic corticosteroids are the first-line treatment for moderate to severe immune checkpoint inhibitor-induced enterocolitis (ICIec). Infliximab (IFX) is recommended for steroid-refractory cases; however, up to 28% of patients do not respond. Repeated-dose IFX regimens may improve outcomes and reduce recurrence, but optimal management strategies remain undefined. Here, we describe a series of patients treated with dashboard-guided IFX for ICIec.

Aims & Methods

A retrospective, descriptive case series was conducted at the IBD clinic of Hospital Universitari Vall d’Hebron between January 2021 and February 2025. The study included adult patients with ICIec who received IFX guided by a pharmacokinetic (pK) model. Demographic and clinical data were collected and analyzed.

Results

The dashboard model was applied in five patients to provide additional guidance for treatment decisions. The median age was 60 years, and three patients were female. The median time between the first immunotherapy dose and development of ICIec was 14.8 weeks. Endoscopy revealed extensive disease in 60% of patients, and 40% also had upper GI involvement. At baseline, 40% had severe inflammation. Median IFX levels at weeks 1 and 2 following the first IFX dose were 23.5 µg/mL and 22.3 µg/mL, respectively. The median interval between the first and second IFX doses was 12 days. Clinical remission was achieved in 4 out of 5 patients (80%). With a median follow-up of 16.7 ± 8 weeks, 4 of 5 patients (80%) remained in clinical remission without ICIec recurrence; one patient died due to an infectious complication.

Conclusion

Dashboard-guided IFX dosing showed benefit in ICIec patients. Use of pharmacokinetic modeling may support more tailored IFX dosing strategies, potentially improving treatment outcomes in a subset of ICIec patients with severe or extensive disease. Prospective studies are needed to better define optimal treatment strategies for ICIec.

Introduction

Inflammatory bowel disease (IBD) significantly impacts patients’ nutritional status and quality of life. Nutritional deficiencies are common in IBD and can worsen disease progression.

Aims & Methods

The aim of this study is to assess the nutritional status of patients with IBD and explore its relationship with quality of life in this cohort. A cross-sectional study conducted at a specialized center assessed nutritional status using the MUST and MIRT tools. For pediatric patients, the "Strong Kids" screening tool was used. A multidisciplinary nutritional intervention was provided, followed by quality of life evaluation using the EQ-5D and IBDQ-32 instruments. Statistical analyses were performed to examine the association between nutritional status and quality of life.

Results

Among 90 IBD patients, 26.6% required hospitalization due to disease flare-ups, primarily adults and females. The median age was 36.7 years (range: 4–81, SD: 32.6), with 58.3% diagnosed with Crohn’s disease and 83.3% requiring biologic therapy (Table 1). The odds ratios (OR) for malnutrition in hospitalized patients were 8.33 (95% CI: 1.16–27) for ulcerative colitis and 25 (95% CI: 11.6–45.2) for Crohn’s disease. All hospitalized adults exhibited poor biochemical control and moderate-to-severe hypoalbuminemia; 25% had sarcopenia. Nutritional support was provided to 49% of patients within the past year. All severely ill hospitalized patients were malnourished.
Pediatric patients, all of whom received nutritional support, demonstrated a higher degree of nutritional compromise. Among these, 25% required parenteral nutrition, while 87.5% received enteral nutrition, primarily with high-calorie, high-protein formulas. During hospitalization, 87.5% gained weight and improved nutritionally, with 75% achieving normal nutritional status at three-month follow-up, although one patient died.
Following the nutritional intervention, over 80% of adults did not experience further nutritional deterioration. In the outpatient cohort, 20 patients were evaluated, of whom 30% were identified as high risk for malnutrition according to MUST, and 25% had nutritional risk (MIRT score ≥3). Patients with poorer initial nutritional status had significantly worse quality of life, with notable impairments in mobility (P = 0.2778; 95% CI: 2.03–64.1), self-care (P = 0.003; 95% CI: 9.45–90.5), daily activities (P = 0.1457; 95% CI: 1.14–58.2), pain/discomfort (P = 0.197; 95% CI: 0.53–53.3), and visual analog scale scores (P = 0.012; 95% CI: 22.9–88.4). Poor nutritional status was also associated with lower quality of life scores on the IBDQ-32 (P = 0.04; 95% CI: 10.3–60.7).

Conclusion

Nutritional status is a key component of IBD management, as malnutrition is linked to poorer quality of life. Screening tools such as MUST and MIRT in adults, and “Strong Kids” in children, are essential for early identification of at-risk patients. Pediatric patients tend to have more severe nutritional compromise than adults, and nutritional support during hospitalization contributes significantly to recovery.

References

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2. Pulley J, Todd A, Flatley C, Begun J. Malnutrition and quality of life among adult inflammatory bowel disease patients. JGH Open. 2019;4(3):454–60.
doi: 10.1002/jgh3.12278.
3. Valvano M, Capannolo A, Cesaro N, et al. Nutrition, Nutritional Status, Micronutrients Deficiency, and Disease Course of Inflammatory Bowel Disease. Nutrients. 2023 Aug 31;15(17):3824. doi: 10.3390/nu15173824.
4. Izquierdo LVP, Orduz-Diaz G, Frías-Ordoñez J, et al. P563 Nutritional screening in patients with inflammatory bowel disease: A challenge in the timely diagnosis of malnutrition and sarcopenia. J Crohns Colitis. 2024;18(Suppl_1). doi: 10.1093/ecco-jcc/jjad212.0693.

Disclosure

None declared