Introduction

Clinical remission of symptoms and endoscopic disease activity were the primary endpoints of two phase-3 studies (LUCENT-1 and -2; NCT03518086 and NCT03524092) in patients with moderately-to-severely active ulcerative colitis (UC) treated with the anti-IL23p19 monoclonal antibody, mirikizumab (miri)(1). This outcome was reached in 24.2% and 49.9% of miri-treated patients at week (W) 12 and 52, respectively. 
In clinical practice, access to endoscopic evaluation can be limited. Measurement of faecal calprotectin (FCP) can be a surrogate biomarker for endoscopic disease activity and therapy response in patients with UC(2). Combined symptom and FCP remission may serve as a surrogate for clinical and endoscopic remission in real-world clinical practice.

Aims & Methods

This post-hoc analysis evaluates the proportion of patients in LUCENT-1/-2 who achieved combined symptom and biomarker remission.
Patients in LUCENT-1 (N=1162) were randomised to receive either 300mg miri (n=868) or placebo (PBO; n=294) intravenously (IV) every 4W (Q4W) for 12W. In LUCENT-2, patients from LUCENT-1 with no clinical response to miri at W12 (N=272) received an extended induction therapy of 300mg miri IV Q4W for 12W (W24 of continuous treatment), while miri-responders (N=544) were randomised to either subcutaneous (SC) 200mg miri (n=365) or PBO (n=179), Q4W for 40W (W52 of continuous treatment).
At W4, W12, W24, and W52, patient symptoms and FCP levels were reported as combined endpoints of symptomatic response or remission (defined in Table 1), with FCP remission (FCP ≤250µg/g). The Cochran-Mantel-Haenszel test compared the treatment groups a) miri and PBO at W4 and W12 from LUCENT-1, and b) miri and PBO at W52 from LUCENT-1 miri-responders. The risk difference and its associated confidence intervals and p-values were reported in Table 1. Non-responder imputation was used for binary variables, while modified baseline observation carried forward was used for continuous variables.

Results

At W4 and W12, 14.2% and 33.2% of the miri group compared to 8.5% and 18.7% of PBO (p=0.0113 and <0.0001, respectively) achieved the combined symptomatic response and biomarker remission endpoint, while 7.3% and 23.7% of the miri group compared to 3.7% and 11.2% of PBO (p=0.0282 and <0.0001, respectively) achieved the combined remission endpoints. At W52, 54.3% of the miri group compared to 27.4% of PBO (p=<0.0001) achieved the combined symptomatic response and biomarker remission endpoint, while 48.5% of the miri group compared to 21.8% of PBO (p=<0.0001) achieved the combined remission endpoints. At W12 and W24, 2.9% and 23.5% of the extended induction group achieved combined symptomatic response and biomarker remission endpoints, respectively, while 1.1% and 13.2% achieved the combined remission endpoints.

Week	Dose	Symptomatic responsea and FCP ≤250 µg/g, n (%)	Common risk difference (CI)b	P-Value	Symptomatic remissionc and FCP ≤250 µg/g, n (%)	Common risk difference (CI)b	P-Value
Week 4	Miri, N=868	123 (14.2)	5.7 (1.7, 9.6)	0.0113	63 (7.3)	3.7 (0.9, 6.4)	0.0282
	PBO, N =294	25 (8.5)			11 (3.7)
Week 12	Miri, N=868	288 (33.2)	14.8 (9.4, 20.2)	<0.0001	206 (23.7)	12.7 (8.1, 17.3)	<0.0001
	PBO, N =294	55 (18.7)			33 (11.2)
Week 52	Miri, N=365	198 (54.3)	25.4 (17.3, 33.6)	<0.0001	177 (48.5)	25.0 (17.3, 32.6)	<0.0001
	PBO, N=179	49 (27.4)			39 (21.8)
Table 1: Proportion of patients with Ulcerative Colitis who achieved combined symptomatic and biomarker endpoints in LUCENT-1/-2 studies aDefined as ≥30% decrease from baseline of the sum of stool frequency (SF) and rectal bleeding (RB) subscores   bCommon risk difference is the percentage difference between miri and PBO adjusted for the baseline factors a) prior biologic or tofacitinib failure (yes/no), b) baseline corticosteroid use (yes/no), c) baseline disease activity (Modified mayo score: [1-6] or [7-9]), and d) region (North America/Europe/Other).  cDefined as SF = 0, or SF = 1 with ≥1 point decrease from baseline and RB = 0

Conclusion

In moderate-severe UC, patients treated with miri demonstrated improved efficacy compared to PBO in combined symptomatic and biomarker response and remission endpoints. Additionally, the data from this post-hoc analysis is consistent with the clinical remission data from LUCENT studies, indicating that this is a suitable endpoint measure in real-world practice.

References

1. D'Haens G, Dubinsky M, Kobayashi T, Irving PM, Howaldt S, Pokrotnieks J, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2023;388(26):2444-55.
2. Bressler B, Panaccione R, Fedorak RN, Seidman EG. Clinicians' guide to the use of fecal calprotectin to identify and monitor disease activity in inflammatory bowel disease. Can J Gastroenterol Hepatol. 2015;29(7):369-72.
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Disclosure

MCF reports payment or honorarium for speaker events: Eli Lilly and Company, Pfzier, AbbVie, Alfa-Sigma, Johnson & Johnson, and Takeda; meeting/travel support: AbbVie, Takeda, and Johnson & Johnson. JG reports grants/contracts: MSD, Janssen, Takeda, Kern Pharma, Sandoz, AbbVie, and GE Healthcare consulting fees: AbbVie, MSD, Jassen, Takeda, Roche, Eli Lilly and Company, Celltrion, Pfizer, Galapagos, GoodGut, and GE Healthcare; payment or honorarium for speaker events: AbbVie, MSD, Janssen, Kern Pharma, Bülhmann, GoodGut, GE Healthcare, Takeda, Eli Lilly and Company, Pfizer, and Galapagos; meeting/travel support: AbbVie, MSD, Janssen, Jern Pahrma, Bülhmann, GE Healthcare, Eli Lilly and Company, and Pfizer. EDM reports grants/contracts: Adacyte Therapeutic; consulting fees: Roche; payment or honorarium for speaker events: Eli Lilly and Company and Adacyte; travel/meeting support Adacyte, Pfizer, Kern Pharma, and AbbVie. CWL reports consulting fees: AbbVie, Janssen, Takeda, Pfizer, Galapagos, GSK, Gilead, Vifor Pharma, Ferring, Dr Falk Pharma, BMS, Boehringer Ingelheim, Eli Lilly and Company, Merck, Novartis, Sandoz, Celltrion, Cellgene, Amgen, Samsung Bioepis, Fresenius Kabi, Tillotts, Kuma Health, and Trellus Health and Iterative Health; payment or honorarium for speaker events: AbbVie, Janssen, Takeda, Pfizer, Galapagos, GSK, Gilead, Vifor Pharma, Ferring, Dr Falk Pharma, BMS, Boehringer Ingelheim, Eli Lilly and Company, Merck, Novartis, Sandoz, Celltrion, Cellgene, Amgen, Samsung Bioepis, Fresenius Kabi, Tillotts, Kuma Health, and Trellus Health and Iterative Health. GS reports consulting fees: AbbVie, Takeda, Johnson & Johnson, Eli Lilly and Company, BMS, Pfizer, and Celltrion; payment or honorarium for speaker events: AbbVie, Takeda, Johnson & Johnson, Eli Lilly and Company, BMS, Pfizer, and Celltrion; participation on data safety monitoring or advisory board: AbbVie, Takeda, Eli Lilly and Company, BMS, and Pfizer; leadership or fiduciary role in committees: ACG training committee, ACG FDA committee, AGA Government Affairs committee, and Crohn’s and Colitis Foundation National Scientific Advisory Committee. ES reports consulting fees: Janssen-Cilag of Johnson & Johnson, Pharmacosmos, Takeda Pharma, AbbVie Deutschland, Pfizer, Tillotts Pharma, AstraZeneca, Galapagos Biopharma, Eli Lilly and Company, Celltrion, DGVS, Dr. Falk Pharma, BMS, Kompetenznetz Darmerkrankungen, and STADA; payment or honorarium for speaker events: Janssen-Cilag of Johnson & Johnson, Pharmacosmos, Takeda, AbbVie Deutschland, Pfizer, Tillotts Pharma, AstraZeneca, Galapagos Biopharma, Eli Lilly and Company, Celltrion, DGVS, Dr. Falk Pharma, BMS, Kompetenznetz Darmerkrankungen, and STADA. DPH reports grants/contracts: Johnson & Johnson and Pfizer; consulting fees: Eli Lilly and Company, AbbVie, Abivax, BMS, Johnson & Johnson, Prometheus, Sanofi, Pfizer, CorEvitas, Fresenius Kabi, Biocon, and Takeda. HG, IR, and ED are employees and minor shareholders in Eli Lilly and Company. AK is an employee of HaaPACS GmBH and a contractor for Eli Lilly and Company.

Introduction

Mirikizumab is a humanized IgG4 monoclonal, anti-interleukin-23p19 antibody. VIVID-2 (NCT04232553), an ongoing open-label study, has demonstrated sustained clinical and endoscopic efficacy at 2 years of treatment of mirikizumab for Crohn’s disease (CD).¹ Here we present the long-term quality of life (QoL) up to 2 years from VIVID-2.

Aims & Methods

Patients enrolled in the phase 3 VIVID-1 study who achieved an endoscopic response to mirikizumab continued maintenance treatment in VIVID-2, while endoscopic non-responders received mirikizumab induction therapy followed by maintenance treatment. Quality of life was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). The proportion of patients who achieved IBDQ response/remission, as well as mean changes from VIVID-1 baseline in IBDQ total scores at W64 and104 were reported. EQ-5D-5L Visual Analog Scale (VAS) scores (range 0-100, with 100 being best imaginable health state) were assessed at W64. Work productivity was assessed at W64 using Work Productivity and Activity Impairment Questionnaire in Crohn's Disease (WPAI:CD) (4 scores including absenteeism, presenteeism, work productivity loss and activity impairment are derived as percentages with higher values indicating greater impairment). Modified non-responder imputation (mNRI) was used for binary missing data imputation, and modified baseline observation carried forward (mBOCF) was used for continuous missing data imputation. Estimates of mean changes from baseline were calculated with analysis of covariance (ANCOVA).

Results

Analysis of endoscopic responders showed IBDQ response and IBDQ remission were maintained through W104 (85.0% and 71.3%, respectively) while endoscopic non-responders also maintained IBDQ response and remission through the same time (72.6% and 60.8%, respectively). (Table 1) Mean change from baseline in IBDQ total score was maintained through W104 for endoscopic responders and non-responders (least squares mean (standard error); 57.2 (2.1) and 46.8 (2.4), respectively). Similarly, EQ-5D-5L VAS improvement was observed for both groups at W64 (27.0 (1.0) and 22.3 (1.2), respectively). WPAI:CD improvements in both groups ranged from −13.9 (1.8) to −34.3 (1.5) for the different scores collected at W64.

Response %a	Endoscopic responders from VIVID-1		Endoscopic non-responders from VIVID-1
	W64	W104	W64	W104
IBDQ Responseb	N=251 90.4	N=251 85.0	N=179 80.4	N=179 72.6
IBDQ Remissionb	N=228 75.1	N=228 71.3	N=158 65.2	N=158 60.8
Abbreviations: IBDQ, Inflammatory Bowel Disease Questionnaire; W, week aPercentage of response is calculated using Rubin's Rules to combine multiple imputation datasets. bIBDQ response and IBDQ remission were defined as ≥16-point improvement from baseline in IBDQ total score and an IBDQ total score of ≥170, respectively.

Table 1: IBDQ Response and Remission among patients receiving mirikizumab through W104

Conclusion

Patients continuing mirikizumab maintenance and those receiving reinduction achieved meaningful long-term QoL improvement that was maintained at 2 years of treatment.

References

1. Barnes E, Sands B, D'Haens G, et al. Long-term efficacy and safety of mirikizumab following 104 weeks of continuous treatment for Crohn's disease: results from the VIVID-2 open-label extension study. Gastroenterology. 2025;168(3 Suppl):S14-S15. doi:10.1053/j.gastro.2025.01.073.

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

Experience as endoscopist, n (%)	< 10 years	7 (33)
	≥ 10 years	14 (67)
Subspecialty, n (%)	IBD	17 (81)
	Advanced endoscopy	1 (5)
	Dual IBD/advanced endoscopy	1 (5)
	General	2 (10)
ADR, median, range (%)		44 (25-68)
APC, median, range		0.83 (0.42-1.9)
DDR, median, range (%)		10 (0-23)
DPC, median, range		0.13 (0-0.30)

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

Placebo	0.36 (0.19,0.69)	0.38 (0.21,0.68)	0.57 (0.31,1.01)	0.34 (0.20,0.60)
	Tofacitinib	1.04 (0.46,2.39)	1.57 (0.69,3.57)	0.96 (0.43,2.11)
		Accelerated Infliximab	1.51 (1.04,2.18)	0.92 (0.69,1.21)
			Cyclosporin	0.61 (0.48,0.78)
				Infliximab

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

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

The prevention of postoperative recurrence (POR) after ileocolonic resection is one of the most relevant issues in the management of Crohn's disease (CD). The role of ustekinumab (UST) and vedolizumab (VEDO) especially in the context of real-life studies is still not entirely clear, often due to small sample sizes, thus requiring further investigation and confirmation.

Aims & Methods

Our real life single-centre retrospective study aims to evaluate the effect of UST and VEDO therapy on prophylaxis of endoscopic recurrence after ileo-colonic resection in CD. In the whole cohort UST or VEDO were used as first-line therapy for prophylaxis of recurrence. All patients (pts) underwent the first endoscopic evaluation within 6-12 months to assess postoperative recurrence (POR), using the Rutgeerts score and were subsequently evaluated at 24 (+-3) months with a second endoscopy. Persistence on therapy two years after the surgery was also evaluated.

Results

64 pts with a mean age of 38 years were included, 25 pts received VEDO (Cohort 1) and 39 UST (Cohort 2).
In the two cohorts, 89% and 91% of pts had been previously resected; 58% and 55% were active smokers. Notably, 100% had already been exposed to one or more biological drugs and the most frequent reason for surgery was the presence of stenosing disease in both cohorts.
In cohort 1, the first post-operative colonoscopy at 6-12 months showed severe POR (RS score >i2) in 28% of pts, all of whom underwent a treatment change at this time point (71% and 29% drug change and VEDO optimisation, respectively). Among the pts who continued the drug (22 pts), the second endoscopy performed at 24 (+-3) months showed severe ROP in 10% of pts, who underwent treatment modification. At ~2 years persistence on therapy in the cohort was 72%.
In cohort 2, the first post-operative colonoscopy at 6-12 months showed severe POR in 25.6% of patients, who changed therapy at this time. Among patients who continued the drug (29 pts), the second endoscopy performed at 24 (+-3) months showed severe POR in 10.3% of pts, who underwent treatment change. At ~2 years persistence on therapy in the cohort was 66.6%. No patients discontinued the drug due to adverse effects in both cohorts.
Comparing the two cohorts regarding severe endoscopic recurrence at 6-12 months and perisistence on therapy at ~2 years, no significant differences emerged between the two groups (p = 1.000, OR: 0.89,IC 95%: 0.29–2.75 and p = 0.86, OR:1.29, IC 95%: 0.43–3.85, respectively).

Conclusion

In our real life cohort of patients with complex CD, ustekinumab and vedolizumab showed high levels of persistence on therapy at ~2 years after surgery. Limited to the small sample population, no significant differences were observed between the two drugs.

Introduction

Bowel urgency (BU) is a bothersome symptom experienced by patients with ulcerative colitis (UC) and is associated with high clinical and quality-of-life burdens. Mirikizumab (MIRI), an anti-IL-23 antibody approved for the treatment of moderately-to-severely active UC, significantly reduced BU severity compared with placebo (PBO), and these improvements were associated with better clinical outcomes.¹ We evaluated the association between incremental improvement in BU severity at Week (W)12 and W52 with other patient-reported outcomes for MIRI-treated patients.

Aims & Methods

In LUCENT-1 (induction), patients were randomized 3:1 to intravenous MIRI 300 mg or PBO every 4 weeks (Q4W) for 12W. MIRI responders during induction were re-randomized 2:1 to subcutaneous MIRI 200 mg or PBO Q4W for 40W in LUCENT-2 (52W of continuous treatment). BU severity was measured using the Urgency Numeric Rating Scale ([UNRS] 0–10). Incremental improvement of BU severity was assessed as reduction of each single point of UNRS score from baseline (BL). The reduction of >7 points was pooled into one category due to sample size. The accumulative benefit of reducing 1 additional point of UNRS score was evaluated at W12 and W52 and was assessed for its association with mean percent improvement in inflammatory bowel disease questionnaire (IBDQ) total score, fatigue NRS, short-form (SF)-36 mental component score (MCS) and physical component score (PCS), and work productivity activity impairment (WPAI) productivity loss.

Results

Significantly greater proportions of patients receiving MIRI achieved UNRS score reduction at certain points versus PBO at W12 and W52. The reduction of each single point of UNRS score was associated with improvement in patient’s physical and mental health, fatigue, work productivity, and quality of life. At W12, fatigue and IBDQ showed greater percent improvements among all the PRO outcomes studied for each 1-point reduction of UNRS. Similar results were observed at W52 (Table 1).

Week 12 (N=868)	UNRS reduction	Fatigue NRS	IBDQ Total Score	MCS	PCS	WPAIa	Week 52 (N=365)	UNRS reduction	Fatigue NRS	IBDQ Total Score	MCS	PCS	WPAIb
	≤0	-11.9	16.0	6.6	9.4	4.9		≤0	8.9	35.9	18.5	21.2	23.9
	1	15.4	25.9	14.6	11.3	16.9		1	5.8	30.6	13.4	12.7	11.2
	2	28.7	31.1	13.7	14.0	20.1		2	32.4	37.5	18.8	18.6	30.1
	3	43.5	35.8	17.9	16.9	24.1		3	59.5	33.9	10.8	20.4	27.5
	4	49.8	49.1	19.7	23.5	24.2		4	62.4	55.6	17.9	33.7	42.1
	5	54.5	43.3	13.1	22.9	28.8		5	52.2	54.0	21.7	27.7	38.2
	6	59.3	55.2	22.1	24.0	36.4		6	68.9	63.0	26.0	26.5	41.9
	7	81.2	64.6	25.9	30.1	29.8		7	83.8	67.3	30.1	30.1	50.6
	>7	73.6	75.4	29.7	39.1	38.5		>7	88.1	87.6	35.0	45.4	54.8

^a Note: N=532, population was restricted to patients with baseline employment status = Yes.
^b Note: N=224, population was restricted to patients with baseline employment status = Yes.
Abbreviations: IBDQ = inflammatory bowel disease questionnaire; MCS = short-form-36 mental component score; N = number of patients in the analysis population; n = number of patients in the specified category; NRS= numeric rating scale; PBO = placebo; PCS = short-form-36 physical component score; UNRS = urgency numeric rating scale; WPAI= work productivity activity impairment productivity loss.
UNRS score was averaged from daily diary entries for a 7-day period. Data were considered as missing for that week if less than 4 days were available.

Conclusion

Incremental improvement in bowel urgency corresponded to improvements in outcomes important to patients, underscoring the importance of managing BU symptoms in improving the quality of life for patients with UC.

References

1. Dubinsky MC, et al. Crohns Colitis 360 2023;5(1):otac044.

Disclosure

MD reports consultancy fees from AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB.
ST reports grants and/or research support from AbbVie, Buhlmann Diagnostics, Celgene, Eli Lilly and Company, the International Organization for the Study of Inflammatory Bowel Disease, Janssen, the Norman Collisson Foundation, Takeda, UCB, and Vifor Pharma; consulting fees from Abacus Pharmaceuticals, AbbVie, Actial, ai4gi, Alcimed, Allergan, Amgen, Arena Pharmaceuticals, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, Atlantic Pharmaceuticals, Barco, Biocare Pharma, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Buhlmann Diagnostics, Calcico, Celgene, Cellerix, Celsius Healthcare, Cerimon Pharmaceuticals, ChemoCentryx, Cisbio, Coronado Biosciences, Cosmo Pharmaceuticals, Ducentis BioTherapeutics, Dynavax, Elan Corporation, Eli Lilly and Company, Enterome, Falk Foundation, Ferring Pharmaceuticals, FPRT Bio, Giuliani, Genentech, Genzyme, GlaxoSmithKline, Glenmark Pharmaceuticals, Grünenthal, GW Pharmaceuticals, Immunocore, Immunometabolism, Indigo Biosciences, Janssen, Lexicon Pharmaceuticals, Medarex, Merck, MSD, Neovacs, Netbiotix, Novartis, Novo Nordisk, NPS Pharma, Ocera Therapeutics, Otsuka, Palau Pharma, Pentax Medical, Pfizer, Philips, Procter & Gamble, Pronota, Proximagen, Ptima Pharma, Receptos, Resolute, Robarts Pharmaceutical, Roche, Sandoz, Santarus, Sensyne Health, Shire, Sigmoid Pharma, SynDermix, Synthon, Takeda, Theravance Biopharma, TiGenix, Tillotts Pharma, TopiVert, TxCell, UCB, Vertex, VHsquared, Vifor Pharma, Warner Chilcott, and Zeria Pharmaceutical; and speaker fees from AbbVie, Amgen, Biogen, Falk Foundation, Ferring Pharmaceuticals, GlaxoSmithKline, Janssen, Shire, Takeda, and Zeria Pharmaceutical.
TK has served as a speaker, a consultant or an advisory board member for AbbVie, Ajinomoto Pharma, Asahi Kasei Medical, Astellas, Alfresa Pharma, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen, JIMRO, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Thermo Scientific, Zeria Pharmaceutical, and received research funding from AbbVie, Alfresa Pharma, Asahi Kasei Medical, EA Pharma, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Sekisui Medical, Thermo Fisher Scientific, Zeria Pharmaceutical.
BA-B has served on advisory board for Bristol Myers Squibb, Pfizer; and reports speaker fees from AbbVie, Takeda, Bristol Myers Squibb, Janssen Pharmaceuticals.
JW, BZ, HQ, CM, SF are employees and minor shareholders of Eli Lilly and Company.
DR reports grant support from Takeda and has served as a consultant for AbbVie, AltruBio, Arena Pharmaceuticals, Bristol Myers Squibb, Eli Lilly and Company, Genentech, Gilead Sciences, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Roche, Takeda, and Techlab.