Introduction

Janus kinase inhibitors (JAKi), including tofacitinib (TOFA, a pan-JAK inhibitor) and filgotinib (FILGO, a selective JAK1 inhibitor), represent an emerging class of orally administered agents for moderate-to-severe ulcerative colitis (UC). Comparative real-world data on their effectiveness and safety are limited.

Aims & Methods

We conducted a multicenter, real-world, propensity score-weighted cohort study using data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). All adult UC patients treated with TOFA or FILGO with ≥16 weeks of follow-up were included. The primary outcomes were steroid-free clinical remission and clinical response at weeks 8 and 24. Treatment persistence and adverse events were also assessed. Inverse Probability of Treatment Weighting (IPTW) was applied to adjust for baseline differences.

Results

A total of 263 patients were included (TOFA: n=171; FILGO: n=92). At week 8, steroid-free clinical remission was achieved in 53.2% of patients treated with TOFA and 43.4% of those treated with FILGO (IPTW-adjusted OR: 1.51; 95% CI: 0.88–2.61; p=0.14). Clinical response at 8 weeks was reported in 75.4% of TOFA-treated patients versus 69.6% in the FILGO group (IPTW-adjusted OR: 1.34; 95% CI: 0.73–2.46; p=0.34). At week 24, steroid-free clinical remission was observed in 58.8% of the TOFA group and 44.9% of the FILGO group (IPTW-adjusted OR: 1.37; 95% CI: 0.76–2.49; p=0.30). Clinical response rates at 24 weeks were 63.6% for TOFA and 59.0% for FILGO (IPTW-adjusted OR: 1.13; 95% CI: 0.62–2.08; p=0.69). IPTW-adjusted Kaplan–Meier and Cox proportional hazards analyses showed no statistically significant difference in the likelihood of treatment discontinuation (log-rank p=0.294; IPTW-adjusted HR for TOFA: 0.78; 95% CI: 0.49–1.25; p=0.30). Adverse event rates were 12.7 and 5.4 per 100 person-years for TOFA and FILGO, respectively, with no significant difference (p=0.152).

Conclusion

In this real-world, IPTW-based study, TOFA and FILGO were well tolerated and demonstrated comparable and high effectiveness and treatment persistence in patients with moderate-to-severe UC, supporting their use as viable oral options in routine clinical practice.

Disclosure

FSM served as an advisory board member and/or received lecture grants from AbbVie, Ferring, Galapagos, Giuliani, Janssen, Lilly, Liohealth s.r.l., Pfizer, Sandoz, Takeda Pharmaceuticals. WF served as an advisory board member and/or received lecture grants from Abbvie, MSD, Takeda, Pfizer, Biogen, Sandoz, Zambon, Ferring, Sofar. AV received lecture grants from Pfizer. MC served as an advisory board member for AbbVie, MSD, Takeda Pharmaceuticals, and received lecture grants from AbbVie, MSD, Chiesi, and Takeda Pharmaceuticals. MC served as an advisory board member for AbbVie, MSD, Takeda Pharmaceuticals, and received lecture grants from AbbVie, MSD, Chiesi, and Takeda Pharmaceuticals. FM served as an advisory board member for Janssen and Galapagos, and received lecture grants from Takeda Pharmaceuticals. SR served as an advisory board member for AbbVie, Janssen, and MSD Pharmaceuticals, and received lecture grants from AbbVie, Galapagos, Janssen, MSD, Pfizer, and Takeda Pharmaceuticals. AO served as an advisory board member for AbbVie, Ferring, Galapagos, Lilly, MSD, Janssen, Pfizer, Samsung Bioepis, and Takeda Pharmaceuticals, and received lecture grants from AbbVie, Fresenius Kabi, Galapagos, Lionheath s.r.l., MSD, Sofar, Chiesi, Janssen, Pfizer, and Takeda Pharmaceuticals. All other authors: nothing to disclose.

Introduction

Despite robust quality indicators such as adenoma detection rate (ADR) in patients without IBD, such indicators for quality in colonoscopy are so far lacking in IBD. The European Society of Gastrointestinal Endoscopy currently recommends a dysplasia detection rate (DDR) of >8%, but evidence base for this is limited.

Aims & Methods

To examine whether existing quality indicators such ADR correlate with endoscopists’ IBD specific quality indicators such as dysplasia detection rate (DDR) and dysplastic lesions per colonoscopy (DPC). Data from consecutive colonoscopies performed by gastroenterologists across 11 tertiary IBD centres were collected, selected if at least 150 non-IBD colonoscopies and 40 IBD-surveillance colonoscopies were performed over a 5-year period. Non-IBD colonoscopies were for patients aged ≥50y, and IBD-colonoscopies for patients meeting national and international criteria for eligibility for dysplasia surveillance. Colonoscopies were excluded if the patient had known dysplasia, a known or suspected familial CRC syndrome, previous colonic resection or severe inflammation in Crohn’s or UC. Correlation between endoscopists’ ADR, adenomas per colonoscopy (APC) in non-IBD colonoscopies with their DDR and DPC in IBD colonoscopies. Secondarily, detection of sessile serrated lesions (SSLs) in patients with and without IBD were analysed.

Results

21 endoscopists (Table 1) met inclusion criteria, who performed 3207 non-IBD colonoscopies and 902 IBD (515 ulcerative colitis [UC] and 387 Crohn’s disease [CD]) colonoscopies. Of the non-IBD colonoscopies, patients’ median age was 65 (IQR 58-73) years, with 1556 (49%) female. Of the IBD-colonoscopies, patients’ median age was 48 (IQR 36-59) years, with 412 (45.7%) female, median disease duration of 14 (IQR 10-21) years. Chromoendoscopy was used in 234 (26%) of IBD colonoscopies. Nontargeted segmental biopsies were performed in 854 IBD colonoscopies, of which 12 (1.42%) detected dysplasia. No cancers were detected in all 902 IBD surveillance colonoscopies.
Key quality indicators for endoscopists are outlined in table 1. ADR correlated with both DDR (Pearson r = 0.44, p = 0.047) and DPC (r = 0.51, p = 0.018). Of the 17 endoscopists with ADR ≥35%, 13 (76%) endoscopists had DDR of ≥ 8%, 6 (35%) had DDR ≥ 12%, and 9 (53%) had a DPC rate of ≥ 0.15. Sessile serrated lesion detection rate (SSLDR) and SSL per colonoscopy (SSLPC) were strongly correlated in both IBD and non IBD endoscopies.

Table 1. Characteristics of 21 endoscopists included for study

Conclusion

Individual endoscopists’ ADRs in patients without IBD correlate with their DPC and DDR in patients with IBD. Further studies are required to assess whether these indicators are correlated with post-colonoscopy colorectal cancer in patients with IBD.

Disclosure

No conflicts of interest to disclose

Introduction

Steroid-refractory acute severe ulcerative colitis (SR-ASUC) is a life-threatening emergency that results in colectomy in approximately 40% of cases.¹ Several medical therapies have emerged as rescue treatments aimed at reducing the need for colectomy.^2-3However, direct comparative studies evaluating the relative efficacy of these therapies remain limited.⁴ This network meta-analysis aims to systematically review and compare the efficacy and safety of available rescue therapies for SR-ASUC, including biologics and small molecule treatments.

Aims & Methods

A systematic literature search was conducted using the MEDLINE, SCOPUS, and CENTRAL databases. Colectomy-free survival probabilities were extracted from Kaplan-Meier curves. A one-stage network meta-analysis using parametric Weibull regression was performed to estimate and compare the relative treatment effects of biologics and small molecule therapies. The primary outcome was colectomy-free survival at 4 and 12 weeks. This study was registered in PROSPERO (CRD420251030353).

Results

A total of 18 studies (5 randomized controlled trials and 13 cohort studies), including 1,706 patients with SR-ASUC, were included. Compared to placebo, standard-dose infliximab [hazard ratio (HR) 0.34, 95% CI: 0.20–0.60, p < 0.001], accelerated-dose infliximab [HR 0.38, 95% CI: 0.21–0.68, p = 0.001], and tofacitinib [HR 0.36, 95% CI: 0.19–0.69, p = 0.002] significantly improved colectomy-free survival. Cyclosporine also showed a trend toward reduced colectomy risk, though it did not reach statistical significance [HR 0.57, 95% CI: 0.31–1.01, p = 0.056]. There were no significant differences in overall adverse events or infection rates among the therapies. Based on SUCRA rankings, colectomy-free survival at both 4 and 12 weeks was highest for tofacitinib (SUCRA: 0.90 and 0.87), followed by accelerated-dose infliximab (0.95 and 0.85), standard-dose infliximab (0.87 and 0.83), and cyclosporine (0.81 and 0.74). (Figure 1 Colectomy free survival probability ; Kaplan-Meier curves)
Table 1. Pairwise table showing comparative efficacy in reducing colectomy risk of biologics and small molecule for SR-ASUC

Conclusion

Tofacitinib and accelerated-dose infliximab appear to be the most effective rescue therapies for improving colectomy-free survival in patients with SR-ASUC.

References

1. Dong C, Metzger M, Holsbø E, et al. Aliment Pharmacol Ther. 2020 Jan;51(1):8-33.
2. Honap S, Jairath V, Sands BE, et al. Gut. 2024 Sep 9;73(10):1763-1773.
3. Calméjane L, Laharie D, Kirchgesner J, et al. United European Gastroenterol J. 2023 Oct;11(8):722-732.
4. Choy MC, Seah D, Faleck DM, et al. Inflamm Bowel Dis. 2019 Jun 18;25(7):1169-1186.

Introduction

Mirikizumab (MIRI) is an anti-IL-23p19 antibody with demonstrated efficacy compared to placebo (PBO) in the treatment of moderately-to-severely active ulcerative colitis (UC) (LUCENT-1: NCT03518086; LUCENT-2: NCT03524092).¹ Prevention of IBD-related surgery and hospitalizations is a goal in disease-modification trials for preventing disease progression.² We described the rates of these events in the LUCENT-1 and -2 trials.

Aims & Methods

Patients were randomized to intravenous MIRI 300 mg or PBO every 4 weeks (Q4W) for induction in LUCENT-1. Patients randomized to MIRI induction and achieving clinical response at Week (W)12 were re-randomized 2:1 in LUCENT-2 to subcutaneous MIRI 200 mg Q4W or PBO (MIRI withdrawal) for maintenance (W12-52). Descriptive statistics were used for proportion of patients in LUCENT-1 and -2 who had hospitalization and/or surgery by treatment group and the exposure-adjusted incident rate (IR). For LUCENT-1, hospitalizations in the induction period and surgeries during the induction and 16-week follow-up period were included. For LUCENT-2, all events were from the on-treatment period. Only hospitalizations associated with an adverse event with ≥24-hour stay (for any causes) were recorded.

Results

MIRI-treated patients had significantly lower IR of overall hospitalization, UC-related hospitalization, and overall surgery vs PBO-treated patients in LUCENT-1 (IR ratio MIRI vs PBO: 0.4, 0.1, 0.4, respectively). IR of UC-related surgery was 1.3 per 100 patient-years in MIRI-treated patients vs 2.6 per 100 patient-years in PBO group (Table). Mean time to first surgery or hospitalization from randomization was 30.5 days for PBO and 58.7 days for MIRI. Additional analyses revealed that patients on MIRI who had surgery/hospitalization in LUCENT-1 or -2 tended to have prior biologic failure and longer duration of disease. Similarly, in LUCENT-2, MIRI-treated patients had significantly lower IR of all-cause hospitalization and similar all-cause surgery vs PBO. No UC-related hospitalization and surgery were reported in the MIRI group while 2 UC-related hospitalizations (1.8 per 100 person-years) were reported from PBO.

Conclusion

Lower rates of UC-related hospitalizations and UC-related surgery were observed in patients treated with MIRI compared to those treated with PBO during the 12W induction LUCENT-1, and that impact continued through the 40W of maintenance LUCENT-2 with no UC-related hospitalizations or UC-related surgery reported in MIRI-treated patients.

References

1. D’Haens G, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. New England Journal of Medicine 2023;388(26):2444-2455.
2. Le Berre C, Peyrin-Biroulet L. Selecting End Points for Disease-Modification Trials in Inflammatory Bowel Disease: the SPIRIT Consensus From the IOIBD. Gastroenterology 2021;160(5):1452-1460.e21.

Disclosure

MR serves as a consultant and on advisory boards for AbbVie, Janssen, Bristol-Myers Squibb, UCB, Takeda, Pfizer, Prometheus Laboratories, Lilly, Celgene, and Amgen.
LPB has served as a consultant for 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, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax; he received grants from Takeda, Fresenius Kabi, Celltrion; he served as a speaker for Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, Medac; he also declares support travel by Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Gossamer Bio, Sandoz, MSD, Amgen, Lilly, Gilead, Thermo Fisher, Medac, CONNECT Biopharm; he declares stock options of Clinical trials Mobile Application.
JW, BZ, IR, KT, CO are employees and minor shareholders of Eli Lilly and Company.
SN has served on advisory board and speaker for Eli Lilly and Company, Pfizer and advisory board for madrigal and speaker for Janssen
TK has served as a paid consultant for Abbvie, Amgen, Biogen, Mundipharma, Hospira, Gilead, Janssen, Pfizer, MSD Sharp & Dome GmbH, and Novartis. He has received reimbursement of meeting participation fees and of travel and accommodation expenses from Abbvie, Janssen, MSD, and Takeda. He has received honoraria for preparing continuing medical education events from Abbvie, Falk, Janssen, MSD, Takeda, and Ferring Arzneimittel GmbH.
LM reports educational grants from Abbvie, Janssen, Pfizer and Takeda; advisory boards: AbbVie, Bristol Myers Squibb, Janssen, and Celltrion; consultant for Abbvie, Pfizer and Pharmacosmos.
FM has served as a speaker and received honoraria from Merck Sharp & Dohme, Abbvie, Vifor, Falk, Laboratorios Vitoria, Ferring, Hospira, and Biogen.

Introduction

The CACTUS-CD study (NCT06125678) prospectively evaluated 407 patients with small bowel Crohn’s disease (CD) and demonstrated that intestinal ultrasound (IUS), particularly smal intestinal contrsat ultrasound (SICUS), could approach the diagnostic accuracy of computed tomography enterography (CTE) and magnetic resonance enterography (MRE)[1]. The value of IUS/SICUS in monitoring of known CD in reference to device assisted enteroscopy (DAE) is not known [2].

Aims & Methods

This post hoc analysis aimed to compare these imaging modalities (IUS, SICUS, CTE/MRE) against DAE for lesion localization and stricture detection in a subset of patients.
Forty-eight patients with established small bowel CD underwent IUS, CTE or MRE, and DAE within one week. Segmental localization (proximal, mid, distal) was assessed across all modalities. Strictures on IUS were defined using wall thickness >3 mm, luminal narrowing <1 cm, and pre-stenotic dilatation[3]. Simplified Magnetic Resonance Index of Activity (MARIA) for MRE, International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) for IUS, and modified Simple Endoscopic Score for Crohn’s Disease (SES-CD) score (0-12, based on ileal subscore) for DAE were compared [2,4,5].

Results

The median age was 42 years (range 18–73), with 43.8% female and a median BMI of 21 kg/m². Among MRE patients (n=22), the median simplified MARIA (Magnetic Resonance Index of Activity) score was 4.5 (range 1-5). IUS revealed a median bowel wall thickness of 5.55 mm (range 2.2-8.6), an median International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) of 63.3 (8.8-87). For DAE, modified Simple Endoscopic Score for Crohn’s Disease (SES-CD) median score was 9 (0-11). Technical success of DAE was 46/48 (95.8%, technical failure: both post operative). The approach of DAE was antegrade (n=16), retrograde (n=26) and bidirectional (n=6). Median depth of maximal insertion was 120 cm (30-600 cm) with median time ​30 minutes (10-240).
All modalities had 100% agreement in distal bowel.In mid-bowel, CTE/MRE and DAE were fully concordant; IUS achieved 72.7%. Proximal agreement was 71.4% for CTE/MRE and 57.1% for IUS. For strictures, CTE/MRE yielded the highest sensitivity (81%), specificity (88%), and agreement (kappa 0.65). IUS had lower sensitivity (47%) but excellent specificity (94%). SICUS performed better than IUS with sensitivity of 75% (p=0.039) and kappa 0.62. Spearman’s correlation showed stronger association of MARIA with SES-CD (r = 0.659, p = 0.001) than IBUS-SAS (r = 0.486, p < 0.001).

Conclusion

Intestinal ultrasound showed excellent concordance with enteroscopy for disease localization in the distal small bowel, supporting its use as a cost-effective, radiation-free, point-of-care modality. The addition of small intestinal contrast ultrasound (SICUS) significantly improved stricture detection. These findings support ultrasound-based strategies as first-line options for monitoring known Crohn’s disease, particularly in settings requiring repeated assessment or where access to cross-sectional imaging and device-assisted enteroscopy is limited.

References

1. Pal P, Mateen MA, Pooja K, et al. S1044 Correlation and Assessment of Small Bowel Lesions Using Cross-Sectional Imaging Techniques vs Small Intestinal Contrast UltraSonography in Known Crohn’s Disease (CACTUS-CD Trial): A Paired, Validating Study (NCT06125678). Official journal of the American College of Gastroenterology | ACG. 2024;119(10S):S731-S732. [10.14309/01.ajg.0001033544.90391.8a]
2. Na JE, Kim HS, Hong SN, et al. Comparison of an Endoscopic Scoring System and the Simplified Magnetic Resonance Index of Activity in Patients with Small Bowel Crohn’s Disease. Gut and Liver. 2024;18(1):97-105.
3. Lu C, Rosentreter R, Parker CE, et al. International expert guidance for defining and monitoring small bowel strictures in Crohn's disease on intestinal ultrasound: a consensus statement. Lancet Gastroenterol Hepatol. 2024;9(12):1101-1110.
4. Novak KL, Nylund K, Maaser C, et al. Expert Consensus on Optimal Acquisition and Development of the International Bowel Ultrasound Segmental Activity Score [IBUS-SAS]: A Reliability and Inter-rater Variability Study on Intestinal Ultrasonography in Crohn's Disease. J Crohns Colitis. 2021;15(4):609-616.
5. Roseira J, Ventosa AR, de Sousa HT, Brito J. The new simplified MARIA score applies beyond clinical trials: A suitable clinical practice tool for Crohn's disease that parallels a simple endoscopic index and fecal calprotectin. United European Gastroenterol J. 2020;8(10):1208-1216.

Introduction

While three JAK inhibitors are now available in Ulcerative Colitis (UC), no direct comparison exists between these drugs making difficult the hierarchization of these therapeutic options.

Aims & Methods

We performed a systematic review and network meta-analysis to compare the short and long-term efficacy of the three available JAK inhibitors (JAKi) (Tofacitinib/TOFA, filgotinib/FILGO, upadacitinib/UPA) in patients with moderat-to-severe UC.
We performed a systematic review and network meta-analysis (PRISMAguidelines) of randomized controlled trials (including post-hoc analyses) conducted in adults, evaluating the efficacy of JAKi in moderate-to-severe UC.
The outcome mesures were 1) steroid-free clinical remission (CFREM) after induction therapy (partial Mayo score ≤ 2), 2) CFREM with endoscopic improvement (endoscopic Mayo score ≤ 1) after induction therapy, 3) CFREM at one year among induction-responders, 4) CFREM at one year among patients in clinical remission after induction.
The network meta-analysis was carried out according to a random effects model. The results are presented as relative risk (RR) with 95% confidence interval. The risk of bias of the studies was assessed according to the Cochrane risk-of-bias tool for randomized trials and overall statistical heterogeneity between studies was assessed using τ .
The SUCRA ranking method (surface under the cumulative ranking) was used to rank the treatments.

Results

Nine studies were included in this network meta-analysis, including a total of 2015 patients.
TOFA 10mg bid, FILGO 200 mg qd and UPA 45mg qd were more effective than placebo to induce CFREM and CFREM with endoscopic improvement. Side-by-side comparisons between JAKi found a higher efficacy of UPA 45 mg qd versus FILGO 200 mg qd (RR=0.22[0.10; 0.45]) for induction but no other significant difference between JAKi. SUCRA ranking hierarchizes induction therapies as following : UPA 45 mg qd (0.99), TOFA 10mg bid (0.75), FILGO 200 mg qd (0.27) and placebo (0.01).
Among induction-responders, all JAKi maintenance regimen (TOFA 10mg bid, TOFA 5mg, bid, FILGO 200mg qd, FILGO 100 mg qd, UPA 30 mg qd, UPA 15 mg qd) were more effective than placebo to achieve CFREM at one year with the following SUCRA ranking : UPA 30mg qd (0.85), TOFA 10mg bid (0.80), FILGO 200 mg qd (0.64), TOFA 5mg bid (0.56), UPA 15 mg (0.44), and placebo (0.01).
Among patients in CFREM after induction phase, all JAKi maintenance regimen (TOFA 10mg bid, TOFA 5mg, bid, FILGO 200mg qd, FILGO 100 mg qd, UPA 30 mg qd, UPA 15 mg qd) were more effective than placebo to achieve CFREM at one year with a different ranking (SUCRA) : TOFA 10 mg bid (0.84), FILGO 200 mg bid (0.74), TOFA (5mg bid) (0 .66), UPA 30mg qd (0.63), UPA 15 mg (0.44) and placebo (0.09).

Conclusion

While this network meta-analysis confirms the efficacy of JAKi to induce and maintain CFREM in moderate-to-severe UC, UPA seems to be the most effective JAKi to induce and maintain CFREM. However, once CFREM achieved after induction, continuing the same dose than during induction such as TOFA (10mg bid) or FILGO 200 mg seems to be more effective than reducing the dose (UPA 30 mg or UPA 15 mg) to maintain remission highlighting the dose-efficacy relationship of JAKi.

Disclosure

Consulting fees from: Abbvie, Amgen, Arena, Biocon, Biogen, Celltrion Healthcare, CTMA, Ferring, Galapagos/AlfaSigma, GutyCare/Resilience Janssen, Lilly, MSD, Nexbiome, Pfizer, Roche, Sandoz, Takeda et Tillotts
Lecture fees from: Abbvie, Amgen, Biogen, Celltrion Healthcare Galapagos/AlfaSigma, Ferring, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Norgine, Pfizer, Roche, Takeda, Tillotts and Vifor Pharma
Research grants/fundings from: Abbvie, Celltrion Healthcare, Janssen, Lessaffre, Lilly, Pfizer, Sandoz and Takeda