Introduction

The subcutaneous (SC) formulation of infliximab offers a patient-centered alternative to the intravenous (IV) route, with the potential to improve treatment adherence, quality of life, and reduce the burden of care in patients with inflammatory bowel disease.

Aims & Methods

Aim of our study was to evaluate the clinical impact, safety, and patients’ outcomes associated with the switch from IV to SC infliximab in routine care. This was a single-center observational study incorporating both prospective and retrospective data collection. Patients with confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) who received at least two infusions of IV infliximab and subsequently transitioned to SC infliximab 120 mg every other week were eligible for inclusion. The primary endpoint was the impact of switching from IV to SC infliximab on patients' quality of life and work productivity measured through the SF-36 and WPAI-GH questionnaires administered at baseline and at week 52. Secondary endpoints included safety profile and clinical effectiveness, defined as clinical remission or improvement at weeks 8, 24 and 52 following the switch to SC infliximab.

Results

A total of 109 adult patients (72 UC (66,1%), 64 male (58.7%)) were enrolled. Median age was 41.6 ± 12.2 years. The switch from IV to SC infliximab was associated with an improvement in work productivity in both UC and CD at week 52 in terms of absenteeism (p = 0.04; η² = 0.18; 95% CI: 0.03–1.00 in CD and p < 0.001; η² = 0.25 in UC) and productivity loss (p < 0.001; η² = 0.47; 95% CI: 0.34–1.00 in CD and p < 0.001; η² = 0.30 in UC) . No significant differences were found in activity impairment, presenteeism, or across SF-36 domains in either CD or UC cohorts (all p > 0.05). Transitioning from IV to SC infliximab did not affect patients’ perceived quality of life as assessed by physical, mental, or social functioning scores. At week 52, 51 out of 55 (93%) patients with UC and 20 out of 27 (74%) patients with CD were in clinical remission. Switching from IV to SC infliximab was significantly associated with achievement of clinical remission over time in UC (χ² = 8.83, p = 0.03 with Cramér’s V = 0.16). In patients with CD, switching from IV to SC infliximab did not show a statistically significant association with the achievement or maintenance of clinical remission at months 12 (χ² = 1.02, p = 0.80 with Cramér’s V = 0.00; 95% CI: 0.00–0.13). The switch was well tolerated with no new safety issues. In total, 6 patients experienced mild adverse events (erythema in the injection site in 3 patients, urinary tract infection in 1 patient, allergic reaction in 1 patient, and skin rash in 1 patient), leading to treatment discontinuation in 3 cases. No patient suffered from severe adverse events.

Conclusion

Switching from IV to SC infliximab is associated with significant improvements in work productivity at week 52 in both UC and CD. No new safety issues were found. These findings support the SC formulation of infliximab as a safe and effective option in the management of inflammatory bowel disease.

Disclosure

G Fiorino received consultancy fees from Ferring, MSD, AbbVie, Takeda, Janssen, Amgen, Sandoz, Samsung Bioepis, Celltrion. LPeyrin‐Biroulet declares personal fees from Galapagos, AbbVie,Janssen,Genentech,Ferring,Tillots,Celltrion,Takeda,Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Inotrem, Allergan, MSD, Roche, Arena, Gilead, Amgen, BMS,Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSE Immunotherapeutics, Enthera, Theravance, PandionTherapeutics,GossamerBio,Viatris, ThermoFisher.Grants fromAbbvie,MSD, Takeda, FreseniusKabi. Stockoptions:CTMA. S Danese has served as a speaker, consultant and advisory board member for Schering‐Plough, AbbVie, MSD, UCB Pharma, Ferring, Cellerix, MilleniumTakeda, Nycomed, Pharma cosmos, Actelion, Alphawasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, NovoNordisk, Cosmo Pharmaceuticals, Vifor and Johnson&Johnson, NikkisoEuropeGMBH, Theravance

Introduction

The PROFILE trial in patients with newly-diagnosed Crohn’s disease demonstrated that “top-down” therapy, with combination infliximab and immunomodulator from diagnosis, provided superior efficacy and a better safety profile over a one-year follow-up period compared to a conventional “accelerated step-up” management approach.

Aims & Methods

The current study aimed to evaluate cost-effectiveness by assessing the healthcare cost and health outcomes associated with starting anti-TNF medication (intravenous infliximab, subcutaneous infliximab, subcutaneous adalimumab) as soon as possible after diagnosis. A de novo Markov model was developed to model the cost-effectiveness of using a “top-down” compared to “accelerated step-up” strategy in adults newly-diagnosed with active Crohn’s disease (HBI score >7, elevated CRP and/or faecal calprotectin >200ug/g and endoscopic evidence of disease activity with simple endoscopic score of Crohn’s disease activity of >6 [>4 if ileal-only disease]). Parameters were informed by individual patient data from PROFILE and data from the published literature. Use of intravenous infliximab, or subcutaneous infliximab, or subcutaneous adalimumab from diagnosis were modelled with biosimilar costs based on average real-world UK contract drug costs ascertained from 18 PROFILE trial sites in 2024. Key model outcomes included healthcare costs (drug acquisition, drug administration, disease management, hospitalisation, surgery) and health outcomes (quality-adjusted life years gained [QALYs]) measured over a 5-year time horizon.

Results

The base case cost-effectiveness analysis indicated that a “top-down” strategy dominated over an “accelerated step-up” approach. Initiating intravenous infliximab from diagnosis yielded greater clinical benefits, with an incremental gain of 0.17 QALYs per patient over a 5-year period, and was less costly, saving £1,681 per patient over the same time frame. Similar clinical benefits were obtained when modelling use of SC infliximab and adalimumab. The greatest cost savings were with adalimumab, totalling £10,059 per patient over 5 years. Sensitivity analyses further supported the robustness of the results for “top-down” therapy, showing it to be the most cost-effective option in 98.7% of model simulations.

Conclusion

This health economic analysis demonstrates that early effective “top-down” treatment with anti-TNF therapy from diagnosis results in lower healthcare resource use compared to an “accelerated step-up” strategy. The economic benefits align with improved clinical outcomes, as early, effective treatment better controls inflammation. Patients experience longer periods in remission, fewer disease-related flares, and enhanced quality of life. These findings were demonstrated for intravenous infliximab, subcutaneous infliximab and subcutaneous adalimumab. In newly-diagnosed patients with active Crohn’s disease, “top-down” treatment with anti-TNF therapy is more efficacious, safer and cost-effective than “accelerated step-up” based treatment strategies.

References

Noor NM, Lee JC, Bond S et al. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol Hepatol. 2024 May;9(5):415-427.

Disclosure

NMN declares educational/travel grants and/or speaker fees from AbbVie, Bristol Myers Squibb, Celltrion, Dr Falk Pharma, Ferring, Galapagos, J&J, Lilly, Pfizer, Pharmacosmos, Takeda and Tillotts Pharma AG.

Introduction

During the COVID-19 pandemic the British Society of Gastroenterology (BSG) introduced interim guidelines supporting a non-biopsy pathway for the diagnosis of coeliac disease. These guidelines reflect the current recommendations of the American Gastroenterological Association (AGA). According to these guidelines, symptomatic or high risk adults with anti-Tissue transglutaminase (TTG) IgA titres ≥10× the upper limit of normal (ULN) and a positive endomysial antibody (EMA) on a repeat sample can be diagnosed without endoscopy and referred directly to a specialist coeliac clinic. Patients who do not meet these criteria should be referred for a gastroscopy (OGD) with biopsy for the confirmation of coeliac, prior to starting a gluten free diet.

Aims & Methods

To assess whether general practitioners (GPs) in the community appropriately referred patients with suspected coeliac disease in line with the AGA and BSG interim non-biopsy diagnostic criteria.
A retrospective review was conducted of all new patients referred to the Coeliac clinic in Galway university hospital between January 2023 and December 2024. Data regarding TTG level at diagnosis, EMA result, and compliance with the diagnostic pathway outlined above was collected for each new referral. This data was collected via Evolve - the hospital's electronic based patient record system.

Results

• There were 119 “new” referrals to our Coeliac Service between January 2023 and December 2024. Of these, 44 cases were known coeliac who were referred by primary care for re-engagement with the clinic, 18 were referred from secondary or tertiary care including GI surgery, Dermatology, Paediatrics, etc. 4 coincidental diagnoses (i.e. OGD performed for indications other than coeliac disease), and 5 outliers (i.e. with incomplete data or incorrectly referred to coeliac clinic) leaving 48 new coeliac cases referred from primary care.
• 18 of these referrals met the non-biopsy criteria for diagnosis (TTG ≥100 + positive EMA)
  • Within this cohort 66% (n=12) were incorrectly referred directly for an OGD which may have delayed the diagnosis of coeliac disease while the remaining 33% (n=6) were correctly referred for direct review at the coeliac clinic.
• The remaining 29 patients all had TTG values less that 10x ULN. 48% (n=14) of these patients were incorrectly referred to clinic prior to endoscopy and of greater concern, 45% (n=13) were recommended by their primary care physician to start a gluten free diet prior to any review or endoscopic procedure.
• Overall, only 44% (n=21) of referrals were compliant with the AGA/BSG guidance.

Conclusion

There is a notable gap in adherence to AGA and BSG non-biopsy coeliac diagnostic guidance in community settings. Half of patients eligible for a non-biopsy diagnosis underwent unnecessary endoscopy, and the majority of ineligible patients were commenced on a gluten free diet prior to, or without, referral for endoscopy. Further GP education is warranted to align referral practices with evidence-based pathways. Dedicated streamlined referral pathways for coeliac disease should ensure a timely diagnosis without mandatory endoscopy in those fulfilling the criteria for a non-biopsy diagnosis and facilitate a timely endoscopy prior to gluten elimination in those who require histological diagnosis.

References

Husby, S., Murray, J.A. and Katzka, D.A. (2019) ‘AGA clinical practice update on diagnosis and monitoring of celiac disease—changing utility of serology and histologic measures: Expert review’, Gastroenterology, 156(4), pp. 885–889. doi:10.1053/j.gastro.2018.12.010.
Tashtoush, L.B. et al. (2021) ‘Letter: The BSG covid‐19 interim coeliac disease guidance no‐biopsy approach is safe in adults’, Alimentary Pharmacology &amp; Therapeutics, 54(8), pp. 1090–1092. doi:10.1111/apt.16553.

Disclosure

No conflict of interest

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.