Introduction

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease of the esophagus. Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, significantly improved histologic and endoscopic outcomes versus placebo in Parts A and B of the EoE KIDS study in pediatric (1–11 years) patients with EoE (NCT04394351).

Aims & Methods

The aim of this analysis was to assess safety and efficacy of long-term dupilumab in the Part C open-label extension (OLE). Patients completing Week (W)52 in Part B were eligible for Part C, where they received the weight-tiered, open-label dupilumab regimen later approved by the FDA (similar to the Part A and B higher-exposure regimen). Part C ended early with FDA approval of dupilumab for pediatric patients with EoE; efficacy data to the last prespecified assessment at W100 are reported.

Results

102 patients enrolled in Part A, 98 in Part B, and 61 in Part C. At W100, the proportions of patients achieving peak esophageal intraepithelial eosinophil counts of ≤6 and <15 eosinophils/high-power field (eos/hpf) were similar/improved vs those observed with higher-exposure dupilumab through W52 of Part B: 70.7% vs 62.9% and 92.7% vs 85.7%, respectively. Additionally, mean (standard deviation) changes from Part A baseline at W100 were similar to those with higher-exposure dupilumab through W52 of Part B in EoE-Histologic Scoring System grade and stage scores (-0.85 [0.39] vs -0.97 [0.39], and -0.85 [0.36] vs -0.89 [0.32], respectively) and EoE-Endoscopic Reference Score (-5.34 [2.54] vs -4.77 [3.08]). Overall, 53/61 (86.9%) patients reported mild or moderate adverse events (AEs) and 3/61 (4.9%) reported serious AEs (none deemed related to dupilumab). The most common treatment-related AE during Part C was injection site reaction.

Conclusion

Dupilumab had a consistent, acceptable safety profile and maintained histologic and endoscopic efficacy in pediatric patients with EoE to W100. Future analyses will evaluate symptoms.

Disclosure

Chehade M: Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, BMS, Nexstone Immunology, Phathom, Recludix Pharma, Regeneron Pharmaceuticals Inc., Sanofi, Shire/Takeda ‒ consultant; Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, Celgene/BMS, Danone, Regeneron Pharmaceuticals Inc., Shire/Takeda ‒ research funding. Dellon ES: Abbvie, Adare/Ellodi, Akesobio, Alfasigma, ALK, Allakos, Amgen, Apollo, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biocryst, Bryn, Calypso, Celgene/Receptos/BMS, Celldex, EsoCap, Eupraxia, Dr. Falk Pharma, Ferring, GI Reviewers, GSK, Holoclara, Invea, Knightpoint, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Sanofi, Shire/Takeda, Target RWE, Upstream Bio – consultant; Allakos, Aqilion, Holoclara, Invea – educational grant. Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Celldex, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Sanofi, Shire/Takeda – research funding; Allakos, Aqilion, Holoclara, Invea – educational grant. Pesek RD: Regeneron Pharmaceuticals Inc. ‒ advisory board. Collins MH: Alimentiv, Allakos, Arena, AstraZeneca, BMS, Calypso, EsoCap, GSK, Regeneron Pharmaceuticals Inc., Shire – consultant. Ashok D: Alexion Pharma, LaunchitDTx, Mirum Pharma ‒ consulting fees. Sanofi ‒ speaker fees. Liu R, Xia C: Regeneron Pharmaceuticals Inc. – employees and shareholders. Louisias M: Sanofi – employees, may hold stock and/or stock options in the company.

Introduction

Vedolizumab (VDZ) is approved for moderate-to-severe inflammatory bowel disease (IBD; ulcerative colitis [UC] & Crohn’s disease [CD]).^1,2 While the subcutaneous (SC) formulation of VDZ is effective as maintenance treatment (mTx) in patients (pts) responding to intravenous (IV) VDZ induction treatment (Tx),^1,3 real-world data on Tx patterns of pts switching mTx from VDZ IV to SC or initiating mTx VDZ SC after IV induction are limited.

Aims & Methods

This prospective, non-interventional, multicentre (NCT05384080) study (conducted under the umbrella VARIETY protocol) enrolled adults with UC or CD initiating/undergoing induction with VDZ IV or continuing VDZ IV mTx, with the option to switch to VDZ SC mTx. The primary endpoint was real-world Tx patterns with VDZ, including Tx persistence. Additional endpoints assessed pt characteristics, pt-reported outcomes, and safety (adverse events [AEs]). Data were descriptively analysed.

Results

Overall, 162 enrolled pts (August 2022–June 2023; UC, n=103; CD, n=59) were included in the interim analysis. At enrolment, 127 (78.4%) received VDZ mTx (UC, n=78; CD, n=49) and 35 (21.6%), VDZ induction (UC, n=25; CD, n=10). The mean (SD) age was 38.2 (12.3) yrs, and time since IBD diagnosis was 10.7 (11.1) yrs. Majority of pts were male (96 [59.3%]), currently employed (124 [76.5%]), had never smoked (109 [67.3%]), and reported previous biologic therapy (95 [58.6%]). Demographic and IBD Tx history data were consistent across cohorts. At baseline, in pts with UC, the mean (SD) partial Mayo score was 1.8 (2.7); in pts with CD, the mean (SD) Crohn’s Disease Activity Index (CDAI) score was 90.6 (70.1). During the 1-yr study period, 20.0% (n=7; UC, n=2; CD, n=5) of pts in the induction and 51.2% (n=65; UC, n=40; CD, n=25) in the mTx cohort switched to VDZ SC. At week (W) 52, Tx persistence was 40.0% (n=14; UC, n=11; CD, n=3) and 77.2% (n=98; UC, n=61; CD, n=37) in the induction and mTx cohorts, respectively, and highest overall in mTx pts who switched to VDZ SC (86.2%; n=56; Table). The most common reason for Tx discontinuation was investigator decision (64.7%; n=33). For VDZ IV and SC, the mean (SD) number of doses per pt was 10.5 (7.6) and 23.8 (15.0), respectively. The median time from VDZ Tx initiation to SC Tx was 383 days (induction: 98 days; mTx: 434 days). In the induction cohort, the mean (SD) Work Productivity & Activity Impairment (WPAI) scores improved from 32.7 (24.1) at baseline (n=21) to 21.5 (31.2) at W52 (n=11), and the Short IBD Questionnaire (SIBDQ) scores improved from 44.1 (10.0) at baseline (n=34) to 51.0 (12.9) at W52 (n=15). In the mTx cohort, WPAI and SIBDQ results remained consistent over time. Fifty-three AEs were reported, including 4 serious AEs (malignancy, IBD flare requiring hospitalization, abdominal abscess, and unconsciousness). One AE of special interest (hypersensitivity reaction) was considered VDZ-related.

Conclusion

In this Polish real-world study, high Tx persistence was reported, especially in pts who switched to VDZ SC. No new safety signals were noted. Overall, the results were consistent with those from other VARIETY cohorts,⁴ although lower persistence was observed during induction. The small size of the induction cohort was a limitation of this study.

References

1. Sandborn WJ, et al. Gastroenterology. 2020;158:562–72.e12.
2. Loftus EV Jr, et al. Aliment Pharmacol Ther. 2020;52:1353–65.
3. Vermeire S, et al. J Crohns Colitis. 2022;16:27–38.
4. Novacek G, et al. J Crohns Colitis. 2024;18(suppl 1):i1506–7

Disclosure

Conflicts of interest: Agata Michalak received lectures fees and/or travel grants from AbbVie, Bayer, Biocodex and Takeda. Katarzyna Karłowicz received lecture fees, consultancy fees or travel educational grants from Bristol Myers Squibb, AbbVie, Polpharma, Takeda and Pfizer. Renata Talar-Wojnarowska received lecture fees and/or travel grants from AbbVie, Astellas, Ferring, Janssen and Takeda. Adam Fabisiak received fees and/or travel grants from Bristol Myers Squibb, Pro. Med. CS, Pfizer and Polpharma. Magdalena Achtenberg received lecture fees from Ferring. Piotr Eder received lecture fees and/or travel grants from Takeda, Ferring, Astellas, Pfizer and Janssen. Maria Kłopocka received payment for lectures from Janssen, Takeda, Ferring, Alfasigma and Pharmabest and travel/accommodation/meeting expenses from Ferring, Janssen, Takeda, Alfasigma and Pharmabest. Maciej Gonciarz received compensation and/or research/educational grants from Pfizer, Polfarma, Abbvie, BMS, Ewoppharma, Ferring, Astellas, Takeda, Jansen-Cilag, Celtrion, Johnson & Johnson, and Sanofi. Grażyna Rydzewska received speaker and consultant fees from AbbVie, AlfaSigma, AstraZeneca, Bayer, Biocodex, Bristol Myers Squibb, Ferring, Janssen, Lilly, Pro. Med. Pl., Recordati, Sanprobi, SOBI and Takeda and travel/accommodation meeting expenses from AbbVie, Ferring and Takeda. Eliza Majewska is a permanent employee of Takeda Pharma Sp. z o.o. Maria Kopertowska-Majchrzak, Tomasz Romańczyk, Halina Cichoż-Lach, Małgorzata Zwolińska-Wcisło, and Elżbieta Poniewierka declare no conflicts of interest.
Funding: The study was funded by Takeda Pharma Sp. z o.o.
Acknowledgements: Medical writing support was provided by Michelle Rebello, PhD, of Cactus Life Sciences (part of Cactus Communications) and funded by Takeda Pharma Sp. z o.o.

Introduction

Resolution of pain, fatigue and other symptoms are key treatment goals for many patients (pts) with Crohn’s disease (CD);^1,2 however, time to symptomatic improvement in pts treated with vedolizumab (VDZ) has not been formally evaluated.

Aims & Methods

VOICE (NCT06249555) is a prospective, observational study in pts with CD aged ≥18 years initiating VDZ or anti-IL-23 antagonist treatment (tx) per product labelling as part of standard of care, with the main objective to explore the time course of response to VDZ as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) domain Short Form (SF) scores. Inclusion criteria include baseline PROMIS Pain Interference (PI)-SF T-score ≥55 (0.5 SD above general population). We enrolled pts via Takeda pt support program in Canada, with additional pts enrolled at US and Canada sites. Planned sample size is 300 pts (VDZ, 200; anti-IL-23 antagonist [reference group not for formal comparison], 100); planned follow-up is 52 weeks (wks), with PROMIS PI data reported weekly for the first 14 wks. The primary endpoint is time to the first meaningful clinical improvement in PROMIS PI-SF T-score, defined as ≥2-point decrease in PROMIS PI-SF T-score from baseline. We also collect data on improvement in 7 PROMIS domains with clinical improvement defined as 5-point (0.5 SD)³ change in T-score from baseline, Short Inflammatory Bowel Disease Questionnaire (SIBDQ; including SIBDQ improvement [≥9 point increase from baseline] and SIBDQ remission [score of ≥60]) and safety. Here, we report the results from pts with ≥1 VDZ dose and ≥1 post-baseline PI assessment included in the interim analysis (IA; prespecified to occur after 50 pts from VDZ group completed or discontinued before the wk 14 assessment to provide an early evaluation of tx response and safety).

Results

Overall, 64 pts with ≥1 VDZ dose and ≥1 post-baseline PROMIS PI assessment (mean±SD age, 43.1±17.0 years, 35.9% male, 92.2% White) were included in the IA. Disease duration (mean±SD) was 6.4±12.1 years; 84.4% of pts were anti-TNF-naïve. Data collection is ongoing for 57 pts (49 with and 8 without completed wk 14 PROMIS PI questionnaire); 7 pts discontinued from the study. The median time to achieve the first ≥2_-point decrease in PROMIS PI-SF T-score (in n=56 pts) was 12 days (95% CI, 6-13). Baseline PROMIS domain scores indicated notable impairment; by wk 14, improvements in mean PROMIS scores from baseline were observed in all 7 measured domains, with ≥5-point improvements in 4/7 domains (Table). At wk 14, 37.5% (24/64) and 7.8% (5/64) pts achieved SIBDQ improvement and remission, respectively. One pt had serious adverse events of appendicitis and diverticulitis, and another pt had a fatal event; none of these were related to VDZ tx.

Table. Summary of PROMIS domain T-scores

Conclusion

The IA results through wk 14 show an early improvement across multiple symptom domains and quality of life in pts with CD starting VDZ tx. Time to first ≥2-point decrease in PROMIS PI-SF T-score was short, with a benefit observed after 12 days from VDZ initiation. Study recruitment and data collection are ongoing.

References

1. Keefer L, et al. Gastroenterology. 2022;162(5):1439-1451.
2. Kitchen H, et al. Crohns Colitis 360. 2020;2(2):otaa033
3. Cella D, et al. Value Health. 2019;22(5):537-544.
4. Shaw BE, et al. Cancer. 2018;124(4):841-849.

Disclosure

This study was sponsored by Alimentiv, Inc.
V. Jairath reports consulting/advisory board fees from AbbVie, Alimentiv, Anaptyis Bio, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ensho, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, MRM Health, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Spyre, Synedgen, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Tillotts and Fresenius Kabi.
M. Long reports consulting fees from AbbVie, Alimentiv, Bristol Myers Squibb, Intercept, Janssen, Lilly, Pfizer, Prometheus, Roivant, Syneos Health and Takeda; and research support from Lilly, Pfizer and Takeda.
M.D. Kappelman reports being a consultant to Eli Lilly and Takeda.
G. Radulescu and N. Li are employees of Alimentiv.
J.J. Wu, I. Romo Bautista, A. Insogna and C. Agboton are employees of Takeda and hold stock and/or share options in Takeda.
N. Narula has received advisory board/consulting honoraria from Abbvie, Amgen, Eli Lilly and Company, Ferring, Fresinius Kabi, Innomar Strategies, Iterative Health, Janssen, Novartis, Organon, Pfizer, Sandoz and Takeda.

Introduction

Crohn’s disease (CD) is a chronic condition characterized by a relapsing-remitting course, often requiring intestinal resection. Postoperative management primarily aims to maintain clinical remission. The advent of biologic therapies has undoubtedly improved disease prognosis following initial surgery. However, access to this therapeutic class remains limited in lower-middle income countries such as Tunisia, necessitating the use of alternative agents, notably azathioprine (AZA), which has been widely used for this indication, albeit with controversial results.

Aims & Methods

This study aimed to evaluate the effectiveness of AZA in maintaining remission after a first intestinal resection in patients with ileal or ileocolonic Crohn’s disease, and to identify factors associated with treatment failure.
​We conducted a retrospective, descriptive, and analytical study in the gastroenterology department of Sahloul University Hospital in Sousse (Tunisia) over a 4-year period (2020–2024). We included all patients with ileal or right ileocolonic CD who underwent intestinal resection and received AZA in the postoperative period.

Results

A total of 66 patients were included, with a mean age at diagnosis of 31.50 ± 12.24 years and a male-to-female ratio of 1.06. The median interval between diagnosis and surgery was 21.5 months. During follow-up, AZA failure occurred in 63.6% of patients (n=42), with a mean time from surgery to failure of 44.71 ± 37.74 months. In univariate analysis, ileocolonic disease location (p=0.042), the total number of flares (p=0.007), and the number of severe flares (p<0.001) prior to surgery were significantly associated with AZA failure. Failure rates were also significantly higher in patients who underwent emergency surgery (p=0.007). Inflammatory resection margins (p<0.001) and severe inflammatory activity (p=0.007) were also significantly associated with treatment failure. In multivariate analysis, three independent risk factors were identified: the number of severe flares before surgery (p=0.031), preoperative inflammatory syndrome (p=0.008), and histopathological evidence of disease at the resection margins (p=0.004).

Conclusion

Our findings suggest that thiopurines remain a valuable therapeutic option in the management of Crohn’s disease, particularly in our setting, where access to alternative therapies is limited and associated with high costs.

Introduction

Sarcoidosis is a multisystem disorder marked by non-caseating granulomas, primarily affecting the lungs but capable of involving almost any organ system. Hepatic involvement is reported in 10-65%, ranging from asymptomatic presentations to severe complications such as chronic cholestasis, portal hypertension, or cirrhosis. Its broad spectrum of clinical presentations makes diagnosis challenging; therefore our hypothesis was that hepatic sarcoidosis is underdiagnosed.

Aims & Methods

This study aims to evaluate the prevalence and clinical characteristics of hepatic sarcoidosis by analyzing two distinct cohorts – a hepatology cohort and a pneumology cohort.
The hepatology cohort included 37 patients from a university hepatology center with clinically and/or histologically confirmed hepatic involvement in sarcoidosis. Clinical characteristics were recorded at initial diagnosis, and at 3- and 12-month follow-up.
In parallel, a pneumology cohort of 346 patients with biopsy-proven sarcoidosis from a pneumology center was examined for abnormal liver values or imaging findings. Regarding this cohort, statistical comparisons between sarcoidosis patients with and without hepatic abnormalities were conducted.

Results

In the hepatology cohort, 43.2% of patients (n = 16) were male and 56.8% (n = 21) female. At initial presentation, the mean BMI was 27.7 ± 7.3 kg/m² (median 25.8; range 19.0–50.5). The number of organ manifestations per patient ranged from 1 to 6, with a median of 3 and a mean of 2.97 ± 1.5; notably, 18.9% of patients (n = 7) presented with isolated hepatic involvement. Liver involvement was biopsy-confirmed in 62.9% of patients (n = 22), whereas only 40% (n = 15) showed corresponding morphological findings on imaging. Laboratory results predominantly showed a cholestatic pattern with elevated ALP and gamma-GT. Mean levels of elevated liver enzymes decreased over the follow-up period. The most common symptoms were fever (27.0%) and weight loss (24.3%), while 16.2% of patients (n = 6) were asymptomatic. 51.3% of patients (n = 19) were treated with glucocorticoids, 43.2% (n = 16) received no therapy.
In the pneumology cohort, 172 (49.7%) sarcoidosis patients showed abnormal liver values or imaging. In the cohort, 139 (40.2%) patients were female, and 207 patients (59.8%) were male. Hepatic abnormalities were observed significantly more frequent in males than females (54% vs. 43%, p = 0.046). Patients with hepatic involvement had a mean age of 52.9 ± 12.0 years (range 20–83) at the time of inpatient stay (n = 172). BMI was significantly higher in patients with hepatic involvement (median 29.8 vs. 27.1 kg/m², p < 0.001), while no significant age difference was observed. Splenic abnormalities were more common in those with hepatic involvement (23.4% vs. 7.7%, p < 0.001).

Conclusion

Analysis of the hepatology cohort highlights that biopsy-confirmed hepatic sarcoidosis can occur even in the absence of corresponding imaging findings. The clinical course of hepatic sarcoidosis is often self-limiting. In selected cases, treatment with glucocorticoids, other immunosuppressants, or ursodeoxycholic acid (UDCA) in patients with cholestatic symptoms is required.
The high number of liver abnormalities in the pneumology cohort suggests that hepatic sarcoidosis is underdiagnosed. Sarcoidosis patients should be assessed for potential hepatic involvement. Screening via ALP levels is recommended. The need to screen for hepatic involvement applies regardless of patient age.

Disclosure

There are no conflict of interest.