Introduction

Identification of patients who are likely to lose response to treatment is crucial in managing Crohn’s disease (CD) and ulcerative colitis (UC).¹ This post hoc analysis of the Phase 3 LIBERTY-CD and -UC trials aimed to characterise patients with moderate-to-severe CD and UC who experienced loss of response (LoR) during maintenance treatment with subcutaneous (SC) infliximab (IFX) up to week (W) 102.²

Aims & Methods

This post hoc analysis included patients in the SC IFX arm in the LIBERTY-CD and -UC trials who responded to induction therapy with IV IFX (evaluated at W10 randomization) then lost response during the maintenance treatment with SC IFX 120 mg every other week (EOW) up to W102. LoR was defined as a Crohn’s Disease Activity Index (CDAI) increase of ≥100 from W10 with a total score of ≥220 for CD, and a modified Mayo score (mMS) increase of ≥2 and ≥30% from W10 with an actual score of ≥5 and a Mayo endoscopic subscore (MES) of ≥2 for UC. Baseline characteristics and clinical profiles at W10 were compared descriptively and predictors for LoR were explored in multivariable regression analysis using variables at baseline and W10.

Results

In the LIBERTY-CD and -UC trials, 64 out of 231 (27.7%) and 75 out of 294 (25.5%) patients experienced LoR to the maintenance therapy with SC IFX 120mg EOW, respectively. In CD, baseline CDAI score (324.2 vs 307.2; p=0.047) and fecal calprotectin (FC; 1093.0 vs 791.0 mg/kg; p=0.021) were higher and C-reactive protein (CRP; 119.5 vs 203.0; p=0.031) were lower in patients who experienced LoR. In UC, baseline disease duration was longer (6.8 vs 3.3 years; p<0.001), neutrophil count (5.2 vs 4.2 x 10⁹ cells/L; p=0.032), prior exposure to biologics or Janus kinase inhibitors (JAKi) (20.0% vs 6.4%; p=0.001), and MES were higher (62.7% vs 43.8%; p=0.005) in patients who experienced LoR. Multivariable regression analysis showed that higher BMI (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.09-2.02; p=0.011), CDAI scores (OR, 1.38; 95% CI, 1.01-1.90; p=0.049) at baseline and reduction in CRP from baseline at week 10 (OR, 1.29; 95% CI, 0.90-1.98; p=0.017) were independently associated with LoR in patients with CD. In UC, prior exposure to biologics and/or JAKi (OR, 3.82; 95% CI, 1.68-8.82; p=0.001) and longer disease duration (OR, 1.35; 95% CI, 1.04-1.77; p=0.023) at baseline were independently associated with LoR. In addition, higher MES at baseline (OR, 1.36; 95% CI, 1.03-1.81; p=0.033) and W10 (OR, 1.47; 95% CI, 1.03-2.12; p=0.034) were predictors for LoR in UC.

Conclusion

Patients who experienced LoR during maintenance therapy with SC IFX 120mg EOW had different patterns of baseline characteristics and clinical profiles at W10 compared to those who did not. BMI and CDAI at baseline, and reduction in CRP from baseline at W10 were predictors of LoR in CD, while prior exposure to biologics and/or JAKi and disease duration at baseline, MES at baseline and W10 were predictors of LoR in UC.

References

¹Vootukuru N, et al. World J Gastroenterol. 2024;30(22):2902-2919.
²Colombel JF, et al. J Crohns Colitis. 2025; jjaf060, https://doi.org/10.1093/ecco-jcc/jjaf060.

Disclosure

MCD: Consultant and Advisor: AbbVie, Abivax, Astra Zeneca, BMS, Celltrion, Eli Lilly, Janssen, Johnson and Johnson, Merck, Pfizer, Prometheus Labs, Roche, Sanofi, Spyre, Takeda. BES: Consulting fees from Abbvie, Adiso Therapeutics, Agomab, Alimentiv , Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Envied Biosciences, Evommune, Ferring, Fresenius Kabi, Fiat, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microbiotica, Mitsubishi Tanabe, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Palisade Bio, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Sorriso Therapeutics, Spyre Therapeutics, Sun Pharma, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences; consulting and speaking fees from Abivax; consulting and speaking fees and other support from Lilly; research grants, consulting and speaking fees and other support from Bristol Myers Squibb, Janssen, Pfizer, Takeda; research grants and consulting fees from Theravance Biopharma; and stock/stock options from Ventyx Biopharma. JFC: Received research grants from AbbVie, Bristol Myers Squibb, Janssen Pharmaceuticals, and Takeda; received payment for lectures from AbbVie and Takeda; received consulting fees from AbbVie, Amgen, AnaptysBio, Allergan, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, GlaxoSmithKline, Genentech (Roche), Janssen Pharmaceuticals, Immunic, Invea, Iterative Scopes, Kaleido Biosciences, Landos, Merck, Microba Life Science, Novartis, Otsuka Pharmaceutical, Pfizer, Protagonist Therapeutics, Prometheus, Sanofi, Seres, Takeda, Teva, TiGenix, and Vifor; and holds stock options in Intestinal Biotech Development. SBH: Consultant, AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, Genentech, Gilead, GSK, Immunic, Janssen, Lilly, Merck, Novartis, Organon, Pfizer, Progenity, Prometheus, Protagonist, Salix, Samsung Bioepis, Seres Therapeutics, Takeda, UCB & VH2; clinical research fees, AbbVie, Amgen, Genentech, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Prometheus, Receptos, Seres Therapeutics, Takeda & UCB; speaker, AbbVie, Janssen, Pfizer & Takeda; review panel member, Intercept Pharmaceuticals; participant on Data Safety Monitoring Board, Boehringer Ingelheim, Bristol Myers Squibb, Gossamer, Protagonist & Ventyx. SS: Advisory committee/board member, AbbVie, Amgen, Arena, Biogen, BMS, Celgene, Celltrion, Falk, Ferring, Fresenius, Galapagos, Gilead, IMAB, Janssen, Lilly, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Sandoz/Hexal, Takeda, Theravance & UCB; lecturer, HIKMA. SD: Consultant, 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 and Vifor; lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer & Takeda. DC, DHK, and YNL: employees of Celltrion Inc. and may own stock in Celltrion. AJY: Steering committee for clinical trial and/or consultant: Takeda, Pfizer, Arena, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Abivax, Johnson and Johnson.

Introduction

Etrasimod is an oral, once-daily (QD), selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Early patient (pt)-reported response is often seen as an indicator of continued improvement through Week (Wk) 12.¹

Aims & Methods

This post hoc analysis investigated relationships between pt-reported symptoms by Day 7 and clinical endpoints at Wk 12 in pts receiving etrasimod 2 mg QD or placebo in the ELEVATE UC clinical programme (NCT03945188, NCT03996369) using rectal bleeding (RB) and stool frequency (SF) subscores reported via daily e-diary records. For pts reporting symptomatic, RB and SF response by Day 7 (yes/no), the proportion achieving clinical endpoints (clinical remission [CR], endoscopic improvement [EI] and EI-histologic remission [EIHR]) at Wk 12 was measured. Adjusted risk differences in proportions of responders between treatment groups were estimated and tested using the Mantel-Haenszel weighted method.

Results

Among pts reporting symptomatic response by Day 7 (etrasimod 2 mg, N1 = 151; placebo, N1 = 60), pts treated with etrasimod vs placebo demonstrated significantly greater CR (47.7% vs 15.0%, adjusted difference [Δ] 33.9, p < 0.001), EI (54.3% vs 20.0%, Δ 35.7, p < 0.001) and EIHR (31.1% vs 6.7%, Δ 24.8, p < 0.001) rates at Wk 12 (Table). In pts who did not demonstrate symptomatic response by Day 7 (etrasimod 2 mg, N1 = 376; placebo, N1 = 200), those treated with etrasimod vs placebo achieved significantly greater rates of CR (18.9% vs 10.0%, Δ 8.7, p = 0.002), EI (27.7% vs 17.0%, Δ 10.5, p = 0.002) and EIHR (16.0% vs 7.5%, Δ 8.3, p = 0.002) at Wk 12 (Table). Similarly, Day 7 RB and SF responders and nonresponders treated with etrasimod vs placebo also demonstrated significantly greater rates of CR, EI and EIHR at Wk 12 (all p < 0.001; Table).

Conclusion

Pts treated with etrasimod may experience rapid symptomatic improvements. In ELEVATE UC, pts treated with etrasimod who both did and did not demonstrate rapid symptomatic improvements had higher rates of clinical endpoint achievement at Wk 12 vs placebo. Pts treated with etrasimod who demonstrated an early, Day 7 response had the greatest likelihood of meeting clinical endpoints at Wk 12.

References

1. Chaparro M et al. J Crohns Colitis 2023; 17: i107–i110.
Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.

Disclosure

MCD reports consulting fees from AbbVie, Abivax, Arena Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Johnson & Johnson, Merck, Pfizer Inc, Prometheus Laboratories, Prometheus Biosciences, Sanofi, Sphyre, Takeda and UCB; is a shareholder/receives royalties from Trellus Health, and has a directorship/ownership interest in Trellus Health.
MC receives speaker/consulting fees and research/education funding from AbbVie, Biogen, Dr. Falk Pharma, Ferring, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer Inc, Shire Pharmaceuticals, Takeda and Tillotts Pharma.
PMI receives grants from Celltrion, Janssen, MSD and Takeda; lecture fees from AbbVie, Bristol Myers Squibb, Celgene, Celltrion, Falk Pharma, Ferring, Galapagos, Gilead, MSD, Janssen, Pfizer Inc, Takeda, Tillotts, Sapphire Medical, Sandoz, Shire and Warner Chilcott; and advisory fees from AbbVie, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer Inc, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Takeda, Topivert, VH2, Vifor Pharma and Warner Chilcott.
PH is an employee of Pfizer Inc, a shareholder of Clene Nanomedicine, Haleon, Idorsia, Liquidia, Longboard Pharmaceuticals, Pfizer Inc and Proctor & Gamble; holds IP/patents for US 2022/0257594 A1; and receives grant/research support from AbbVie, Bristol Myers Squibb, Buhlmann, Janssen, Lilly, Pfizer Inc and Takeda.
SS, JCW, and WW are employees and shareholders of Pfizer Inc.
MG is an employee of Pfizer AG and shareholder of Pfizer Inc.
JT receives advisory board fees from AbbVie, Lilly, Janssen and Pfizer Inc; research grants from AbbVie and Janssen; and speaker fees from AbbVie, Janssen, Lilly, Takeda and Pfizer Inc.
RP receives consulting fees from Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer Inc, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx and UCB; speaker's fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer Inc, Roche, Sandoz, Shire and Takeda Pharmaceuticals; advisory board fees from AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer Inc, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals and Ventyx; and grant/research support from AbbVie, Janssen, Takeda and Pfizer Inc.

Introduction

Etrasimod (2 mg/day, oral) is a novel alternative for moderate-to-severe active ulcerative colitis (UC), which has proved to be effective in ELEVATE UC12 and UC52 trials^1,2.

Aims & Methods

This cost-effectiveness analysis compared etrasimod vs. most frequently used biologics in Spain³, for patients with moderate-to-severe active UC experienced to advanced therapies (AT), from the perspective of the Spanish national health system.
A hybrid model simulated the induction (decision tree) and maintenance (Markov model, 8-week cycles during lifetime) phases treatment to estimate costs (€, 2025) and quality-adjusted life years (QALYs), both yearly discounted (3%). All model inputs derived from scientific literature and were validated by national experts. The patients’ characteristics proceeded from etrasimod trials^1,2. Rates of efficacy, safety, and loss of response of etrasimod, adalimumab, ustekinumab, intravenous (IV) vedolizumab and subcutaneous (SC) vedolizumab were obtained from a Bayesian network meta-analysis^4,5.
After loss of response, a loop of subsequent AT in perpetuity was applied. Total costs included drugs acquisition (authorized posology and dose intensifications when required, both based on the European Public Assessment Reports [EPARs])^6,7, IV administration (€77.16)⁸, adverse events (€5,964.49 per serious infection)⁸ and management of UC (cost): active UC (€4,471)^9,10, response without remission (€1,801)^9,10, remission (€762)^9,10, surgery (€4,448)⁹, post-surgery without complications (€1,101)^9,10 and with complications (€6,428)^9,10. The annual surgery rate in UC was 0.34%¹⁰ (urgent: 38.2%; elective: 61.8%)¹¹, early and late complications occurred in 18.4%¹² and 46% (for 6.5 years)¹³. Utility values were 0.78 for active UC^1,2, 0.82 for response without remission^1,2, 0.89 for remission^1,2, 0.74 for surgery¹⁴, 0.90 for post-surgery without complications¹⁴ and 0.71 with complications¹⁴. Concomitant treatment with azathioprine (35% patients, biologics only), mercaptopurine (15% patients, biologics only), mesalazine (40% patients), prednisone (20% patients) and beclomethasone (10% patients) were considered^7,15. In addition to age and sex-specific mortality in Spain¹⁶, the excess mortality associated with colectomy was considered (relative risk: 1.3)¹⁷. A probabilistic sensitivity analysis (PSA) tested the results’ robustness.

Results

Etrasimod yielded more QALYs compared to each biologic and produced cost-savings in all pairwise comparisons except for IV vedolizumab (Table 1). Thus, etrasimod was cost-effective compared to IV vedolizumab (€16,212/QALY), and dominant compared with all remaining biologics. PSA revealed that etrasimod was dominant compared to each biologic (average of Monte Carlo simulations). Under a willingness to pay threshold of €27,000/QALY¹⁸, etrasimod was cost-effective in a minimum of 58.5% simulations (vs. IV vedolizumab) and a maximum of 99.9% (vs. adalimumab), varying between pairwise comparisons of etrasimod vs. biologic.

Conclusion

Etrasimod represents a cost-effective alternative for AT-experienced patients with moderate-to-severe active UC compared with biologics available in Spain.

References

¹ https://clinicaltrials.gov/study/NCT03945188; ² Sandborn WJ. Lancet. 2023;401:1159–71; ³ Gómez-Labrador C. Pharmaceutics. 2024;16:629; ⁴ Jaraith V. J Comp Eff Res. 2025:e240225; ⁵ https://scientificpubs.congressposter.com/p/k0b1nw0im7astcj2; ⁶ https://cima.aemps.es/cima/publico/home.html; ⁷ https://botplusweb.farmaceuticos.com/; ⁸ https://esalud.oblikue.com/; ⁹ Trigo-Vicente C. Expert Rev Pharmacoecon Outcomes Res. 2018;18:321–9; ¹⁰ Guasch M. Dig Liver Dis. 2021;53:54–60; ¹¹ Núñez L. Gastroenterol Hepatol. 2023;46:369–75; ¹² García MJ. J Clin Med. 2021;10:4402; ¹³ Ferrante M. Inflamm Bowel Dis. 2008;14:20–8; ¹⁴ Kosmas C. Value Health. 2015;18:A630; ¹⁵ https://www.nice.org.uk/guidance/ta828; ¹⁶ https://ine.es/dyngs/INEbase/es/operacion.htm?c=Estadistica_C&cid=1254736177004&menu=ultiDatos&idp=1254735573002; ¹⁷ Jess T. Am J Gastroenterol. 2007;102:609–17; ¹⁸ Vallejo-Torres L. PharmacoEconomics. 2025;43:109-22.

Disclosure

This work was sponsored by Pfizer®.
IRL, FMN, AJLV and EMB have received fees for their scientific advice and contribution to the publication.
AC and ALJ are employees of Pfizer SLU.
ACG and IO are employees of Pharmacoeconomics & Outcomes Research Iberia (PORIB), a consultant company specializing in health economics and outcomes research, which has received fees from Pfizer SLU for conducting the present study.
IRL has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Alfasigma, Biogen, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Johnson & Johnson, Eli Lilly, Mirum Pharmaceuticals, Merck, Pfizer, Roche, Takeda, and Tillotts Pharma.

Introduction

Previous studies reported a positive correlation between serum and tissue drug levels in IBD receiving intravenous (IV) infliximab (IFX) therapy, except in those with severely inflamed tissue (1). Tissue drug levels in patients with IBD receiving SC IFX have not yet been investigated. We aimed to compare both the serum and tissue drug levels between SC and IV IFX maintenance therapy in IBD patients.

Aims & Methods

Any IBD patients under maintenance therapy with SC or IV stable doses IFX who underwent a colonoscopy for routine follow-up were eligible. Patient and disease characteristics, as well as clinical and endoscopic activity were recorded. Clinical activity was defined by high activity score (CDAI or pMAYO score) with at least one elevated biomarker (fecal calprotectin >250 mg/g, serum CRP >5 mg/L). Endoscopic disease activity was categorized as absent (normal), low (mild inflammation), moderate (friability, aphthoid lesions), or severe (ulcerations), as reported by the endoscopist blinded to the results of serum and tissue drug levels. Two biopsies were taken from the same location (either the most active area or randomly if no endoscopic lesion), and tissue and serum IFX levels were measured simultaneously in a centralized manner blinded to clinical and endoscopic disease activity. Frozen biopsy specimens were treated with the Bio-Plex® Cell Lysis Kit after tissue cutting and homogenates were sonicated at 4°C (Omni Ruptor 205). Tissue extracts were then frozen at -80°C prior drug measurements (iTrack10; Theradiag).

Results

Thirty-five patients were enrolled (CD in 65%, Sex ratio 1.4, 14 % with clinically and 57 % with endoscopically active disease, and 23 under SC IFX therapy). The characteristics of both IV and SC IFX groups were comparable, except for drug dose intensification in 90% of those treated with IV IFX group and 5% in the SC IFX cohort (p < 0.001). In patient in endoscopic remission, tissue levels were undetectable or very low for both IV and SC IFX therapy. Serum and tissue drug levels were significantly higher in the SC IFX cohort compared with the IV IFX group (22 mg/mL vs 9 mg/mL for serum; p < 0.001 and 25 mg/g vs 10 mg/g for tissue; p = 0.002, respectively). A moderate correlation was found between serum and tissue drug levels for both IV and SC IFX therapy (Spearman r = 0.42; p = 0.014 and r = 0.43; p = 0.001, respectively). Tissue drug levels increased gradually in patients with minimal or moderate endoscopic activity and were lower in those with severe endoscopic activity for both IV and SC IFX groups (p < 0.001). Tissue drug levels remained significantly higher in minimal or moderate endoscopically active disease in SC compared with IV route of IFX administration. The two independent factors associated with drug tissue levels > 14 mg/g (median levels) were the SC IFX route (OR: 2.25, 95% CI = [1.19–2.23]; p = 0.001) and the serum IFX levels (OR: 1.63, 95% CI = [1.19–2.23]; p = 0.002). A serum IFX level greater than 16.1 mg/mL was highly predictive of a tissue drug level > 14 mg/g tissue (Se: 0.94, Spe: 0.94, PPV: 0.94, NPV: 0.94, and Accuracy = 94.3%).

Conclusion

Serum and tissue drug levels are positively correlated in IBD patients under IV and SC maintenance IFX therapy. Interestingly, drug levels were higher both in serum and tissue in patients under SC IFX compared with IV IFX and tissue drug levels gradually increased in minimally to moderately inflamed intestine but were lower or undetectable in more severe inflamed areas.

References

1. Yarur AJ, et al. The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS study. Gut 2016; 65: 249-255.

Introduction

An increasing number of patients in clinical practice are transitioning from intravenous (IV) to subcutaneous (SC) dosing of infliximab. In this simulation study, we evaluated hypothetical dosing scenarios for both (normal to obese) adults and children switching from steady-state IV to SC infliximab, as well as those initiating SC infliximab therapy.

Aims & Methods

By combining two previous published infliximab models (1,2) we were able to simulate both IV and SC dosing in adults and children. Various dosing regimens were simulated using a large virtual population. In each scenario, the distribution of trough concentrations and area under the plasma concentration time curve (AUC) was calculated.

Results

Peak levels were higher after IV dosing compared to SC dosing, while trough levels were higher after SC dosing leading to more stable infliximab levels over time. Overall exposure remained largely similar when switching from a standard IV to SC dosing regimen. Patients with a high body mass index and those on high-frequency IV dosing regimens of infliximab demonstrated reduced exposure when transitioned to the fixed SC dose. Paediatric patients exhibited higher exposure on the fixed SC dose. Simulation of SC induction schemes demonstrated early achievement of steady state plasma levels.

Conclusion

Infliximab exposure (AUC) remains largely similar when transitioning from standard IV to SC dosing. Current dosing regimens may not be optimal for morbidly obese patients, paediatric patients and patients on high-frequency infliximab regimens. These findings provide a foundation for future clinical research to refine SC infliximab dosing in these populations.

References

1) Hanzel J, Bukkems LH, Gecse KB, D’Haens GR, Mathôt RAA. Population pharmacokinetics of subcutaneous infliximab CT-P13 in Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther. 2021;54:1309–19.
2) Fasanmade AA, Adedokun OJ, Blank M, Zhou H, Davis HM. Pharmacokinetic Properties of Infliximab in Children and Adults with Crohn’s Disease: A Retrospective Analysis of Data from 2 Phase III Clinical Trials. Clin Ther. 2011;33:946–64.

Disclosure

RW has no conflicts of interest. RK is an employee and stockholder of Insight RX, a company developing clinical decision software. LD has served as a speaker for AbbVie, Celltrion, Janssen-Cilag and Takeda and has developed continuing education materials for Ferring, all outside the submitted work.

Introduction

The current universal standard of care in primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), although its clinical benefit in PBC has never been reported in absolute measures.

Aims & Methods

This cohort aimed to assess the prevalence of incomplete response to UDCA and determine non-response predictors.
Patients with PBC as main diagnosis were included from the hospital's centralized electronic medical records system, over a 10-year period. Overlap syndromes (PBC-Auto-Immune Hepatitis) were also included. Main endpoints included incomplete response to UDCA treatment according to Paris I, Paris II criteria, and Globe score.

Results

A total of 50 patients were included in this study. The mean age at diagnosis was 52.74 years (24-73 years) and 92% females. Only one patient was asymptomatic at onset and 82% had positive anti‐mitochondrial antibodies. All patients were treated with ursodeoxycholic acid (UDCA). Corticosteroids and immunosuppressive therapies were associated in 26% of cases. Incomplete response to UDCA was observed in 28% and 34% of patients according to Paris I and II criteria, respectively. Non-response predictors were poor therapeutic adherence, Overlap syndrome and hepatocellular carcinoma in 14%, 6% and 4% respectively. Five patients were lost to follow-up and five cases died from cirrhosis ’complications. The median ΔGLOBE score was 0.42 (IQR: -1.58 to 3.92). The 5, 10 and 15 years liver transplantation-free survival (median) was: +10%, +7.38% and +5% respectively. Liver transplantation (LT) was considered in one patient with excellent outcomes at last follow-up.

Conclusion

A considerable proportion of patients showed incomplete response to UDCA treatment according to Paris II criteria. Early identification of patients at risk of incomplete response could improve patient management and overall disease prognosis.

References

- Treatment response to ursodeoxycholic acid in primary biliary cholangitis: A systematic review and meta-analysis. DOI: 10.1016/j.dld.2022.12.010
- Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score. doi: 10.1016/S2468-1253(18)30163-8. Epub 2018 Jul 13.