Introduction

Mirikizumab, a monoclonal antibody targeting the p19 subunit of IL-23, was approved in Germany in May 2024 for the treatment of moderately to severely active ulcerative colitis (UC), following favorable results in clinical trials (1,2). We aimed to evaluate the effectiveness and safety of mirikizumab (MIRI) in a real-world setting, focusing on a population of patients with prior exposure to three or more advanced therapies.

Aims & Methods

​​​​​In October 2023, we initiated a prospective observational study, collecting clinical, biochemical, and endoscopic data from adult patients (n > 100) with moderate to severe UC who began MIRI treatment in our tertiary referral center in Munich, Germany. The primary endpoints were clinical remission, defined as a Clinical Activity Index (CAI, Lichtiger score) <4 and endoscopic remission, defined as an endoscopic Mayo score ≤1 at 12 months. Secondary outcomes included monthly (1-4 mo) and bimonthly (6-12 mo) trends in fecal calprotectin levels, CAI scores, urgency numeric rating scale (NRS), frequency of re-induction therapy (300 mg every 4 weeks for 3 doses), and steroid discontinuation during the observation period. Adverse events were systematically recorded. All statistical analysis was performed by SolidPulse Software in Phyton using pandas, scipy and statsmodels. This report presents the first key results from patients who have completed at least 6 months of treatment.

Results

To date, 73 patients have initiated MIRI therapy as approved; none have discontinued treatment. Of these, 55 patients have reached the 6-month follow-up. These 55 had a median disease duration of 11 years (range 3–43), and 55% were female. All 55 patients had been exposed to three or more advanced therapies before starting MIRI, and 23 patients (42%) received MIRI concomitantly in combination with another targeted therapy. Among the 55 patients, 29 (53%) had previously lost response to ustekinumab (90 mg every 8 weeks), and 19 (35%) were on concomitant corticosteroids at the start of MIRI therapy. At baseline, 36 patients had a Mayo endoscopic score of II or III, and 19 had a score of 0 or I.
Main results:

• The rates of clinical remission (CAI <4) increased from 36% (30/55) at baseline to 42% (23/55) at 1 month (p=0,6), 40% (22/55) at 2 months (p=0,8), 49% (27/55) at 3 months (p=0,09), 58% (32/55) at 4 months (p=0,008), and 58% (32/55) at 6 months (p=0.008, McNemar test).
• Median urgency NRS scores improved from 5 (range 0–10) at baseline to 1 (range 0–9) at 6 months (p<0.0001, two-sided Wilcoxon test).
• Median calprotectin decreased from 460 (range 20–2100) at baseline to 75 (range 20–2100) at 6 months (p<0.0001, two-sided Wilcoxon test).
• Among the 29 patients with prior ustekinumab use, clinical remission increased from 41% (12/29) at baseline to 55% (16/29) at 6 months, though this change did not reach statistical significance (p = 0.3, McNemar test), possibly due to the low number of patients.

Conclusion

Mirikizumab demonstrated clinical effectiveness and was well tolerated in a real-world UC cohort, including patients with longstanding disease and multiple prior treatments with advanced therapies.

References

1) D’Haens G, Dubinsky M, Kobayashi T et al. Mirikizumab as induction and maintenance therapy for ulcerative colitis. NEJM. 2023; 388: 2444–2455.
2) Dubinsky MC, Clemow DB, Hunter Gibble T et al. Clinical effect of mirikizumab treatment on bowel urgency in patients with moderately to severely active ulcerative colitis and the clinical relevance of bowel urgency improvement for disease remission. Crohn's Colitis 360. 2023; 360: 1–13.

Disclosure

This work has been funded by a grant from Eli Lilly

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

Introduction

In complex perianal fistulizing Crohn’s disease (PFCD), rectal involvement is associated with worse outcomes, likely due to persistent inflammation at fistula internal openings. It is linked to lower remission rates and higher failure rates after anti-TNF-alpha induction, and current guidelines consider it a contraindication to surgical repair. However, its predictive value for secondary loss of response (LOR) to anti-TNF-alpha therapy remains unclear. While endoscopy and MRI can assess rectal disease, the former is limited to mucosal findings, whereas MRI provides comprehensive evaluation of transmural and pelvic inflammation.

Aims & Methods

This study aimed to assess the predictive value of rectal involvement for secondary LOR using both modalities. We conducted a longitudinal study (2000–2023) at a tertiary inflammatory bowel disease center. Included were PFCD patients naïve to anti-TNF-alpha therapy who achieved response or remission after induction. Patients with inadequate follow-up or poor adherence were excluded. Rectal involvement was defined as wall thickening >3 mm on MRI, and mucosal inflammation, a single ulcer >5 mm, or ≥3 ulcers <5 mm on endoscopy. Patients were stratified by MRI findings. Logistic regression identified predictors of secondary LOR, and Kaplan–Meier analysis assessed recurrence-free survival (RFS).

Results

A total of 80 patients were included (male-to-female ratio: 1.33). MRI-detected rectal wall thickening was present in 49 patients (61.3%). The two groups were comparable in baseline demographics and disease phenotype. Mean age at Crohn’s disease diagnosis was 28.9 years in the thickening group and 27.4 years in the non-thickening group; mean age at PFCD onset was 32.5 and 31.5 years, respectively. Most patients were treated with infliximab (88%), and the remainder received adalimumab (12%). Endoscopic rectal involvement was documented in 37 patients (46.3%). Secondary LOR occurred in 64.3% of patients overall, with a mean time to LOR of 17.8 months. Notably, MRI-defined rectal thickening was independently associated with increased odds of LOR (OR = 6.35, p = 0.002), whereas endoscopic assessment did not show a significant association. Patients without MRI-defined thickening had significantly higher RFS at 12, 36, and 60 months (86%, 72%, 57%) compared to those with rectal thickening (57%, 35%, 28%; p < 0.001).

Conclusion

Baseline MRI-detected rectal thickening is a strong, independent predictor of secondary LOR and reduced RFS in PFCD. MRI should be integrated into early disease assessment to identify high-risk patients who may benefit from intensified therapy and close monitoring. Resolution of rectal inflammation may restore eligibility for surgical repair. Further prospective studies comparing MRI and endoscopic markers are warranted to guide tailored treatment strategies.

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

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.