Introduction

The prevalence of IBD is rising in racial and ethnic minorities and in countries with previous low prevalence. There are limited studies of this disease in Latin America and the Caribbean.

Aims & Methods

This cross-sectional, retrospective study used de-identified insurance claims from commercial health insurers in PR. Cases identified had ICD-10 codes for IBD and at least one of the following criteria: 2 hospitalizations for IBD, 4 IBD-related physician visits, one IBD drug claim plus one of the former, or 2 ambulatory center IBD claims plus one of the former .Variables include age, gender, insurance type (Medicare Advantage or commercial insurance), IBD diagnosis, IBD-related physician visits, endoscopies, emergency room visits, hospitalizations and surgery. Point prevalence was defined as a new and pre-existing case during a 12-month period over the average number of insured population for each year of the study period. Estimates are presented as the number of cases per 100,000 insured individuals with 95% confidence intervals (CI) using Poisson regression. The study was approved by the MSC-IRB. We aim to estimate the point prevalence of IBD in an insured population in Puerto Rico (PR) from 2018 to 2022.

Results

The average insured population for the study period was 1,764,543. IBD was identified in 6,293 individuals; 35.6% had Crohn’s disease (CD), 61% had ulcerative colitis (UC), and 3.4% were undetermined IBD. The overall prevalence of IBD was 356.6/100,000; prevalence was 127.1/100,000 for CD, and 217.5/100,000 for UC. Yearly prevalence rates showed an upward trend from 2018 to 2021 and a slight decrease in 2022. In 2018, the prevalence was 147.0/100,000 (95% CI: 145.33-148.68), increasing to 175.4/100,000 (95% CI: 173.45-177.35) in 2019 and 188.8/100,000 (95% CI: 186.77-190.89) in 2020. The peak prevalence occurred in 2021 at 215.0/100,000 (95% CI: 212.8-217.23), followed by a decrease to 199.9/100,000 (95% CI: 197.83-201.93) in 2022.

Conclusion

The increase in IBD prevalence in PR from 2018 to 2021, peaking at 215.0/100,000, aligns with previous studies suggesting an increasing disease burden on the island. An analysis for 2013 reported 181.5/100,000 across all insurance types including Medicaid. The peak in 2021 may reflect improved diagnosis, increased disease awareness, or better access following pandemic-related healthcare disruptions. The slight decline in 2022 prevalence may reflect a shift in insurance status, immigration, or a decrease in healthcare access. Continued monitoring of IBD prevalence is essential to track long-term trends, given the considerable rise since the early 2000s. Our findings place PR within the recent rising global trends of this disease and underscores the need for ongoing research and targeted healthcare strategies. The Medicaid insured population is being studied and should provide a more complete vision of IBD in PR.

References

Torres EA, Torres-Cintron M, Velazquez S, Vendrell R, Del Valle A, Pérez C M. Prevalence of Inflammatory Bowel Diseases in Puerto Rico: A Health Care Claims Analysis of  an Insured Population. PR Health Sci J 2021;40(3):103–109.
Ye Y, Manne S, Treem WR, Bennett D. Prevalence of Inflammatory Bowel Disease in Pediatric and Adult Populations: Recent Estimates From Large National Databases in the United States, 2007–2016. Inflamm Bowel Dis 2020;26:619-625.
Vendrell R, Venegas HL, Perez CM, Morell C, Roman RV, Torres EA. Differences in prevalence of Inflammatory Bowel Disease in Puerto Rico between commercial and government-sponsored managed health care insured individuals. Bol Asoc Med PR 2013;105(2) :15-19.

Introduction

While inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), affects people of all sexes, potential disparities in the diagnostic process—such as differences in symptom onset, symptom reporting, and time to diagnosis—have not been systematically investigated in depth to date.

Aims & Methods

This analysis aims to explore potential sex differences in the pre-diagnostic symptom presentation and the diagnostic pathway of IBD, spanning from the onset of first symptoms to the eventual clinical diagnosis. In this interim analysis of a multicenter cross-sectional study, data of 1180 participants with IBD (women: n=770, men: n=410) from 42 recruiting units all over Germany were included. A comprehensive set of demographic data was collected via an online survey, encompassing the following variables: the IBD entity, sex and gender identity, age, the initial symptoms of IBD, the time from symptom onset to first consultation, the time from first consultation to referral, and the time to diagnosis. In addition, the respective physician's sex was documented. Moreover, the distinct disease-related and therapeutic histories have been collected. Inclusion criteria were a minimum age of 18 years and a confirmed diagnosis of UC or CD for a minimum of three months.

Results

No significant sex differences were observed in the median time to initial physician consultation for either CD or UC (CD: women 3 months [IQR: 1–12], men 3 months [IQR: 0.5–10], p=0.567, g=0.1; UC: women 2 months [IQR: 0.8–5], men 1.3 months [IQR: 0.5–4], p=0.091, g=0.1). Similarly, the median time from first consultation to referral did not differ significantly between sexes (CD: women 1.5 months [IQR: 0.5–5], men 1 month [IQR: 0.5–6], p=0.154, g=0.1; UC: women 0.8 months [IQR: 0.3–3], men 0.5 months [IQR: 0.2–1], p=0.113, g=0.2).
However, women experienced significantly longer median time from symptom onset to final IBD diagnosis compared to men (CD: women 12 months [IQR: 5–48], men 6.5 months [IQR: 2.5–24], p=0.002, g=0.3; UC: women 5 months [IQR: 2–14.5], men 3 months [IQR: 1.3–8], p=0.006, g=0.2). The misdiagnosis rate was found to be significantly higher in women with IBD than in men (IBD women: n=311 (40.4%); IBD men: n=141 (34.4%); p=0.044). Furthermore, sex-specific differences in the initial presentation of symptoms were observed. Women with CD were more likely to present with diarrhea (p=0.005, ϕ =0), nausea (p=0.013, ϕ=0), or arthralgia (p=0.012, ϕ =0) compared to CD men. In UC, women were more likely to initially experience fever (p < 0.001, ϕ = 0) or abdominal pain (p = 0.004, ϕ = 0) compared to men.

Conclusion

Despite similar timelines for initial physician contact and referral, women with IBD experienced significantly longer diagnostic delays and higher rates of misdiagnoses than men. Sex-specific differences in initial symptom presentation were observed, suggesting that diagnostic disparities may be partly driven by variations in symptom profiles and their interpretation. These challenges call for a broader, global perspective and increased awareness to improve the overall care of individuals with IBD on an international scale.

Introduction

Mesenchymal stem cells (MSCs) exhibit immunomodulatory properties through Treg induction^[1], yet their clinical efficacy varies across gastrointestinal immune disorders^[2]. This study integrates systematic evidence from 79 MSC-GVHD trials with preclinical IBD models to identify critical determinants of MSC therapeutic success.

Aims & Methods

• Clinical Analysis: Meta-analysis of 79 trials (4,710 patients) evaluating MSC efficacy in GVHD, stratified by MSC source (bone marrow vs. umbilical cord), dosing, and disease severity.
• Preclinical Validation: DSS-induced murine colitis treated with human umbilical cord-derived MSCs (hUCB-MSCs; 2×10^6 cells/IP, n=8/group). Outcomes included histopathology, Treg quantification (flow cytometry), and IDO/PGE2 mechanisms (qPCR/ELISA).

Results

1. GVHD Clinical Data:
   • Umbilical cord MSCs showed superior 1-year survival vs. bone marrow sources (76% vs. 47%, p=0.016) in steroid-refractory GVHD.
   • Pediatric patients exhibited 71.2% response rate with early MSC intervention (<48h post-diagnosis).
2. IBD Preclinical Findings:
   • hUCB-MSCs reduced colitis activity index by 67% (p=0.003) and increased colonic Foxp3+ Tregs 3.2-fold vs. controls (p=0.017).
   • IFN-γ priming enhanced hUCB-MSC immunosuppression via IDO↑ (4.8-fold, p=0.008) and PGE2↑ (2.1-fold, p=0.03).

Conclusion

MSCs demonstrate disease-specific therapeutic hierarchies: Umbilical cord-derived cells optimized for acute GVHD and IBD through Treg/IDO/PGE2 axis activation. Timing (early intervention) and inflammatory priming (IFN-γ) are critical modulators. These insights warrant phase II trials of IFN-γ-primed UCMSCs for immune-mediated gastroenterological diseases.

References

[1]Zhang M, Johnson-Stephenson TK, Wang W, Wang Y, Li J, Li L, Zen K, Chen X, Zhu D. Mesenchymal stem cell-derived exosome-educated macrophages alleviate systemic lupus erythematosus by promoting efferocytosis and recruitment of IL-17⁺ regulatory T cell. Stem Cell Res Ther. 2022 Sep 24;13(1):484.
[2]Wang Y, Huang B, Jin T, Ocansey DKW, Jiang J, Mao F. Intestinal Fibrosis in Inflammatory Bowel Disease and the Prospects of Mesenchymal Stem Cell Therapy. Front Immunol. 2022 Mar 18;13:835005.

Introduction

No data exist on the relationship between serum and tissue infliximab (IFX) concentrations and outcomes in acute severe ulcerative colitis (ASUC).

Aims & Methods

In hospitalized patients (pts) with ASUC treated with IFX rescue therapy, we assessed relationships between longitudinal serum and tissue IFX concentrations and pt outcomes. In an open-label, prospective study, hospitalized ASUC pts treated with IFX rescue therapy were followed for 22 weeks (wks) at 2 centers. Inclusion criteria: (A) hospitalized ASUC (partial Mayo score [PMS] > 7, baseline Mayo endoscopic score [MES] ≥ 2 and met Truelove/Witts criteria) (B) receiving either standard or accelerated rescue IFX. From IFX initiation until wk 22, clinical scores (PMS) and serum sampling were performed at multiple induction and maintenance timepoints (hospital/outpatient). Colonoscopy scores (MES) and biopsies were collected on day 2-5 post first infusion (early inpatient) and wk 16-22 (maintenance). Outcomes: Median area under the curve (AUC) of serum IFX concentration during early induction (wk 0-2), induction (wk 0-14) and maintenance (wk 15-22) were compared between wk 22 endoscopic remitters (ERs) (MES 0 or 1 without UC-related hospitalization or colectomy) and non-remitters (NRs). Tissue IFX concentrations were compared between groups.

Results

110 serum samples over 22 wks (mean 7.9 samples/pt) with 54 samples between wk 0- 2 (mean= 3.9/pt) were collected. Biopsies at early inpatient (n=17) and maintenance colonoscopies (n=15) were collected from 14 pts. Mean age was 38 years, 50% were female, mean disease duration was 7.8 years and 69% had pancolitis. One NR needed colectomy and another was re-hospitalized. 50% achieved endoscopic remission at wk 22. ERs had numerically higher baseline CRP (49 [±28] vs. 31 [±24] mg/dL), immunomodulator use (71% vs. 43%) and clinical response (86% vs. 43%) to NRs, while albumin (3.3 [±0.9] vs. 2.9 [±0.6] g/dL) and total IFX dose between wk 0-2 (16 [±1] vs. 12 [±6] mg/kg) were more similar. Mean BMI was 23.8 kg/m². Between wk 0-2, the mean number of IFX infusions per pt was 1.5 (±0.7), and median dose per infusion was 11.4 mg/kg (IQR 25-75: 11-19). Median serum IFX concentration AUC was higher in ERs than NRs in early induction (wk 0-2: 568 ug*day/mL [528-1627] vs. 293 [145- 423], p=0.004), all induction (wk 0-14: 3036 [2742-3199] vs. 1768 [1375-2468] p=0.004) and in maintenance (wk 15-22: 841 [309-3295] vs. 405 [295-718] p=0.002). Findings were similar for dose normalized AUC. Peak concentration 2 hrs post first infusion was numerically higher in ERs vs. NRs (median 365 ug/mL [200-484] vs. 187 [140-355] p=0.15) overall and dose-adjusted. Anti- IFX antibodies were detected in one NR maintenance sample. Baseline clearance inversely correlated with AUC (r=-0.7, p=0.03) or dose-normalized induction AUC (r=-0.8, p=0.01). Tissue IFX concentrations were similar in inflamed/non-inflamed tissue and were similar between ERs/NRs in early induction (median 104 ng/mg [89-114] vs. 107 [76-133], p=1.0), and maintenance (10 [4-69] vs. 26 [3-87], p=0.99). Percent of drug in tissue vs. serum was similar between ERs/NRs (induction: median 7% vs 8%; maintenance: 8% vs 6%).

Conclusion

Intense serum and tissue sampling of ASUC pts receiving IFX showed higher serum drug exposure at all timepoints in endoscopic remitters whereas tissue concentrations were similar regardless of outcome. Tissue IFX may be required but not sufficient for achievement of outcomes in ASUC.

Disclosure

PC, SS, and LE report no conflicts of interest.
PL, MR, MS, MF and WT are employees of Alimentiv Inc
RB Speaker/consulting/moderator: Bristol Myers Squibb, Janssen, AbbVie, Takeda, Ferring, Celltrion, Pfizer, Merck, Eli Lilly. Advisory boards: Celltrion, AbbVie, Pfizer, Janssen, Bristol Myers Squibb, Takeda, Merck, Eli Lilly. Educational grants and educational sponsorships: Abbvie, Johnson and Johnson Innovative Medicine, Pfizer, Eli Lilly, Amgen, Pendopharm, Merck, Celltrion, Organon. Travel support: Pfizer, Celltrion, Johnson and Johnson Innovative Medicine, Abbvie.
WA reports consulting fees and participation on advisory board from Johnson & Johnson and Takeda Pharmaceuticals, Inc.
BB reports consulting fees and participation on advisory board from Bristol Myers Squibb, Abbvie, Merck and has grant funding from Merck, Mirador, Prometheus, and Gilead.
PD reports consulting fees from Alimentiv.
MD M. Duijvestein reports speaking fee from Bristol Meyers Squibb, Takeda, Galapagos, Janssen, Dr. Falk, advisory board feest form Abbvie, Bristol Meyers Squibb, Celltrion, Galapagos/Alfasigma, Janssen, Takeda and grant/Research support: Pfizer, Bristol Meyers Squibb, Galapagos Alfasigma, Janssen
MSS Speaker for Abbvie, Janssen, Takeda, Pfizer, Ferring, Novartis, and Lilly. Advisor for Abbvie, Janssen, Takeda, Pfizer, Ferring, Gilead, Amgen, Merck, and Lilly. Research for Abbvie, Janssen, Takeda, Pfizer, and Gilead. Consults for Abbvie, Janssen, Takeda, Pfizer, and Lilly.
RL Consultant for Xencor, Sanofi. SAB member for CJ Biosciences, Ancilia, and Montage Bio.
DL consulting: Abbvie, AltruBio, BMS, Boehringer Ingelheim, Eli Lilly, Johnson & Johnson, PSI, Palatin, Pfizer, Prime, Takeda, Vedanta. Speaking fees: Abbvie, Johnson & Johnson; Grants: Boehringer Ingelheim, Johnson & Johnson.
ES has obtained grant/research support from Abbott (AbbVie), AstraZeneca, CCFA, Janssen Research &Development, Johns Hopkins University, National Institute of Diabetes and Digestive and Kidney (NIDDK), National Institute of Health (NIH), New York Crohn’s Foundation, Pfizer, UCB, UCSF–CCFA Clinical Research Alliance, Genentech. Seres Therapeutics, Celgene Corporation. Consulting fees are reported for AbbVie, Crohn’s and Colitis Foundation of America (CCFA), Entera Health, Evidera, GI Health Foundation, Janssen, Protagonist Therapeutics, Seres Health, Takeda Pharmaceuticals, Bristol Myers Squibb. Stock shareholder of Gilead, and honoraria of GIHealth Foundation for non-branded speaker’s bureau, Janssen for non-branded speaker’s bureau.
BGF reports consulting fees from AbbVie,Abivax,Adiso,AgomAB Therapeutics,Allianthera,Amgen,AnaptysBio,Arena Pharma,Avoro Capital Advisors,Atomwise,,BioJamp,Biora Therapeutics,Blackbird Laboratories,Boehringer-Ingelheim,Boxer Capital,Celsius Therapeutics,Celgene/BMS,Connect BioPharma,Cytoki,Disc Medicine,Duality,EcoR1,Eli Lilly,Equillium,Ermium,First Wave,Forbion,Galapagos,Galen Atlantica,Genentech/Roche,Gilead,Gossamer Pharma,GSK,Hinge Bio,Index Pharma,Imhotex,Immunic Therapeutics,Intercept,JAKAcademy,Janssen,Japan Tobacco Inc.,Kaleido Biosciences,Klick Health,Landos Biopharma,Lenczner Slaght,LifeSci Capital,Lument AB,Mage Biologics,Mestag,Millennium,MiroBio,Monte Rose Tx,Morgan Lewis,Morphic Therapeutics,Mylan,Nexys Therapeutics,Nimbus Therapeutics,OM Pharma,OrbiMed Origo BioPharma,Orphagen,Pandion Therapeutics,Pendopharm,Pfizer,Prometheus Therapeutics and Diagnostics (Merck),Progenity,Protagonist,PTM Therapeutics,Q32 Bio,Rebiotix,REDX,Roche,Roivant/Televant,Sandoz,Sanofi,Seres Therapeutics,Silverback Therapeutics,Sobi,Spyre Therapeutics,Surrozen Inc.,Synedgen,Takeda,Teva,Thelium,Tigenix,Tillotts,Triastek,Ventyx; lecture fees from Takeda,Janssen,and AbbVie; participation on advisory board for AbbVie,AnaptysBio,Boehringer-Ingelheim,Celgene/BMS,Eli Lilly,Genentech/Roche,Janssen,Merck,MiroBio,Origo BioPharma,Pfizer,REDX Pharma,Sanofi,Takeda,Teva,Ecor1Capital,Morphic,GSK; stock or stock options from Evida,EnGene,and Connect Biopharma.
WS reports consulting fees from Alimentiv, Eli Lilly, Forbion, Prometheus Biosciences, Prometheus Laboratories, Shoreline Biosciences, Ventyx Biosciences; stock or stock options from Eli Lilly, Prometheus Biosciences, Prometheus Laboratories, Shoreline Biosciences, Mirador Therapeutics, Ventyx Biosciences; and employee at Mirador Therapeutics and Ventyx Biosciences. Spouse: Eli Lilly – stock, Merck - employee; Prometheus Laboratories – stock, stock options; Ventyx Biosciences – stock, stock options
VJ reports consulting fees and participation on advisory board for AbbVie, Alimentiv, Altrubio, Amgen, AnaptysBio, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, BiomeBank, Boehringer Ingelheim, Bristol Myers Squibb, Calluna Pharma, Celltrion, Eli Lilly, Endpoint Health, Ensho Therapeutics, Enthera, Exeliom Biosciences, Ferring, Flagship Pioneering, Fresenius Kabi, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, MRM Health, Nxera Therapeutics, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Roivant, Sandoz, Sanofi, Second Genome, Sorriso, Spyre Therapeutics, Takeda, Teva, Tillotts, Ventyx, Vividion; speaker fees from AbbVie, Ferring, Bristol Myers Squibb, Galapagos, Janssen, Pfizer, Takeda, Tillotts, and Fresenius Kabi.
NVC reports research grants from R-Biopharm and consulting fees from AcelaBio, Alimentiv, Pfizer, ProciseDX, Prometheus Biosciences, and Spyre Therapeutics. NVC is a current employee of Mirador Therapeutics.

Introduction

In this 12-month maintenance period analysis of the FilgoColitis study, we report on clinical effectiveness and psychosocial outcomes in ulcerative colitis (UC) patients newly initiated on filgotinib (FIL) therapy in a real-world setting. In addition, this study attempts to define novel patient-based outcomes monitored by wearable devices.

Aims & Methods

FilgoColitis is a prospective, multicentre, non-interventional, 24-month observational study in patients with active UC and newly introduced FIL therapy. Disease activity (response: reduction of pMayo by >3 points from baseline to month 6 and a reduction of at least 30% or reaching remission at month 6; clinical remission (CR): pMayo ≤ 1 plus a bleeding subscore=0; steroid-free remission: CR and no systemic use of steroids or oral budesonide) and quality of life (QoL) (sIBDQ and EQ-5D) will be analysed. In a subset, physical activity will be analysed using two different wearable devices (Garmin® smartwatch and SensMotion® accelerometer) with complete wearable data available for the two days immediately following both baseline and month 12 (n=17).

Results

202 UC patients with a newly introduced filgotinib therapy were enrolled in the study. After excluding missing outcomes, six patients were excluded due to incomplete baseline data. Out of the participants with complete baseline data (n=196), 106 (54.1%) used at least one wearable device during the study. To validate the smartwatch, all steps measured in parallel by both the smartwatch and the conventional accelerometer system were compared halfway through the recruitment period and showed good agreement with a positive correlation of 0.88 (p<0.001). Of the 196 patients with UC at baseline, 59.7% were male, and the median time since diagnosis was 8.0 years. Before treatment with FIL, 84.2% of patients had received biologic or small molecule therapies, and 55.6% had used immunosuppressants. Treatment persistence of these 196 baseline FIL patients at month 12 was 59.7% (Kaplan-Meier analysis). Of these 140 patients with complete baseline and month 12 data were available for the 12-month effectiveness analyses. After 12 months of treatment with FIL, the rates of clinical remission and steroid-free remission were 44.3% and 41.4%, respectively (Table 1, mITT analyses with switchers as outcome failures). There was no significant difference in clinical remission between biologic-naïve and biologic-experienced patients (50.0% vs 43.4%). Looking at week-10 responders only, the remission rate at month 12 was 66.2%. QoL improved significantly, with median EQ-VAS scores increasing from 68 to 80 at month 12 (p<0.001), and sIBDQ scores improving from 41.0 to 56.0 (p<0.001). In patients who were in remission at month 12, the number of steps measured during the night was lower than in patients who were not in remission: 170 (75-272) vs 342 (94-620). This was consistent with patients' reports of nocturnal bowel movements (0% versus 33.4%).

Table 1. Effectiveness of filgotinib therapy in UC patients at month 12 (mITT)

Conclusion

In this real-world study, FIL demonstrated a clinical remission rate of 44.3% at month 12 in patients with active UC, demonstrating a further improvement compared to the induction phase (CR 29.2% at week 10). QoL was also significantly improved.

Disclosure

BB has received consulting fees from: AbbVie, MSD, Shire, Ferring, Hospira, Takeda, Movetis, Shield Therapeutics, Pfizer, Biogen, Janssen, Hexal, and Celgene, outside the submitted work. Financial support for lectures and teaching from: AbbVie, Ferring, MSD, Merckle, Falk, HLR, Shield Therapeutics, Pfizer, Celltrion, Takeda, Janssen, and Mundipharma, outside the submitted work. Grant and financial support for research from AbbVie and Ferring, outside the submitted work.
SPD does not have any relevant financial or non-financial interests to disclose.
TH does not have any relevant financial or non-financial interests to disclose.
WL does not have any relevant financial or non-financial interests to disclose.
MK has received personal fees from AbbVie, Ferring, BMS, Galapagos, Janssen, and Amgen, outside the submitted work.
RE has received personal fees from: Takeda, AbbVie, MSD, Biogen, Hexal, Amgen, Celltrion, and Viatris, outside the submitted work.
LZ does not have any relevant financial or non-financial interests to disclose.
AS does not have any relevant financial or non-financial interests to disclose.
PE has received personal fees from: AbbVie, BMS, Galapagos, Janssen, and Amgen, outside the submitted work.
JR does not have any relevant financial or non-financial interests to disclose.
SFS does not have any relevant financial or non-financial interests to disclose.
TW does not have any relevant financial or non-financial interests to disclose.
SS has received personal fees from AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, IMAB, Gilead, HIMA, IMAB-Biopharma, MSD, Mylan, Pfizer, Fresenius, Janssen, Takeda, Theravance, Provention Bio, Protagonist, and Falk, outside the submitted work.