Introduction

Prompt initiation of advanced therapy (AT) medications, encompassing biologics and small molecule treatments, is crucial for the effective treatment of inflammatory bowel disease (IBD). The time taken from the decision to start the AT to it’s first administration, or time to advanced therapy (TAT), can vary significantly between individuals negatively impacting upon their disease course. However, our knowledge of the causes for the variation in TAT is poor.

Aims & Methods

We aimed to investigate the impact that different demographic and disease-related factors have on the TAT. A retrospective analysis of electronic patient records, conducted at a tertiary IBD referral centre in London in March 2024, analysed electronic patient records of all those over the age of 18 currently being treated for IBD with an AT and collected data on the TAT for their index AT, defined as the number of days from the documented decision to start an AT to the date of the first administration. Data was also collected on multiple variables which including disease type, type of AT, age, sex, ethnicity and socioeconomic status by analysing patients’ Index of Multiple Deprivation (IMD). A multiple negative binomial regression was performed entering all variables together to assess their relative effect on TAT.

Results

1298 patients were identified and 485 were excluded due to either their index AT being started elsewhere, incomplete data, a positive screening test or because they were enrolled in a clinical trial. The multiple binomial regression found that TAT was significantly longer for those of non-white ethnicity (p=0.039) (table 1). Analysis for patients of black ethnicity found an Incident Rate Ratio (IRR) of 1.46 (95% CI 1.09,1.95), for mixed ethnicity IRR=1.26 (95% CI 0.77,2.05) and for asian ethnicity IRR=1.17 (95% CI 0.96, 1.41) when compared to white patients. Treatment with adalimumab was also associated with a longer TAT (p=<0.001, IRR 1.37, 95% CI 0.95,1.96) but no other factors were statistically significant: IMD p=0.133; age p=0.155; sex p=0.702; disease type p=0.335.

Conclusion

Our study has identified that non-white ethnicity is associated with a longer TAT and this may be a contributing factor to worse outcomes in patients with IBD from an ethnic minority background. Further research into the causes for this are required to help address this health disparity.

Introduction

Mirikizumab is an anti-IL-23p19 antibody with demonstrated efficacy compared to placebo in the treatment of moderately to severely active ulcerative colitis (UC) (LUCENT-1: NCT03518086; LUCENT-2: NCT03524092). Corticosteroid (CS)-free remission is a treatment goal for patients with UC. Mirikizumab’s CS-sparing effect was assessed in the LUCENT-2 maintenance trial among patients receiving CS at baseline.

Aims & Methods

In LUCENT-1, patients on mirikizumab or placebo who entered the study on CS remained on their stable baseline dose (≤20 mg/day prednisone equivalent) during induction (Week [W] 0 to W12). Patients randomized to mirikizumab induction and achieving clinical response (N=365) at W12 were re-randomized 2:1 in LUCENT-2 to mirikizumab (200 mg/4 weeks) or placebo for maintenance (W12-52). LUCENT-1 responders began a CS taper upon entering LUCENT-2 by tapering the >10 mg daily dose by 5 mg/week until receiving 10 mg/day, and then 2.5 mg/week until 0 mg/day. For those receiving ≤10 mg/day, the daily dose was tapered by 2.5 mg/week until 0 mg/day. Clinical remission was defined as a Mayo stool frequency subscore of 0 or 1 with ≥1-point decrease from W0 baseline, a rectal bleeding subscore of 0, and an endoscopic subscore of 0 or 1 (excluding friability). Descriptive statistics were calculated with non-responder imputation used for missing data. The common risk difference between mirikizumab and placebo was calculated and adjusted for the following stratification factors: prior biologic/tofacitinib failure, region, and W12 clinical remission status. Risk difference confidence intervals were calculated with the Mantel-Haenszel-Sato method. P-values were calculated with the Cochran-Mantel-Haenszel test adjusted by prior biologic/tofacitinib failure and W0 CS use.

Results

Of the mirikizumab induction responders who were re-randomized in LUCENT-2, 33% (59/179) of placebo patients were baseline CS users compared with 34% (125/365) of mirikizumab patients. The median baseline CS dose was 20 mg/day. At W52, a significantly greater proportion of patients treated with mirikizumab in maintenance achieved clinical remission while off CS at W52 vs placebo, clinical remission while off CS for ≥12 weeks, and clinical remission with symptomatic remission at W40 while off CS for ≥12 weeks (Table; all p≤0.01). A significantly greater proportion of patients treated with mirikizumab had discontinued CS by W24, W40, and W52 compared to placebo (Table; all p<0.001). Among patients who completed W52 of mirikizumab treatment, 95.2% had discontinued CS.

Conclusion

Among patients on CS at baseline, mirikizumab induction responders who were re-randomized to mirikizumab maintenance achieved CS-free clinical remission at W52 at higher rates than mirikizumab induction responders who were re-randomized to placebo maintenance. Mirikizumab’s CS-sparing effect in patients with moderately to severely active UC is clinically meaningful and aligned with long-term treatment goals of CS discontinuation.

Disclosure

David Laharie declares counseling, boards, transports, or fees from AbbVie, Biogaran, Biogen, Ferring, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Theradiag, and Tillots. Corey Siegel has served as a consultant to AbbVie, BMS, Eli Lilly, Janssen, Pfizer, Prometheus, Takeda, and Trellus Health, as a speaker for AbbVie, Janssen, Pfizer, and Takeda, and received grant support from AbbVie, Janssen, Pfizer, and Takeda. Karen Samaan, Deborah A. Fisher, Nathan Morris, and Isabel Redondo are employees and shareholders of Eli Lilly and Company. Parambir S. Dulai has received research support and/or consulting fees from Takeda, Janssen, Pfizer, AbbVie, Gilead, Eli Lilly, BMS, Novartis; owns stock options and has served as a board member for DigbiHealth; and owns licensing royalties from Precidiag. Vipul Jairath has received consulting fees from AbbVie, Alimentiv Inc (formerly Robarts Clinical Trials), Arena Pharmaceuticals, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pendopharm, Pfzer, Roche, Sandoz, Takeda, Topivert; speaker’s fees from Abbvie, Ferring, Janssen, Pfzer, Shire, and Takeda. Javier P. Gisbert has served as a speaker, a consultant, and advisory member for, or has received research funding from MSD, AbbVie, Hospira, Pfizer, Kern Pharma, Biogen, Takeda, Janssen, Roche, Sandoz, Celgene, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, and Vifor Pharma. Katsuyoshi Matsuoka reports receiving personal fees from Mitsubishi Tanabe Pharma, AbbVie, Takeda Pharmaceutical, EA Pharma, Janssen Pharmaceutical, and Pfizer, research grants from Janssen Pharmaceutical, and scholarship grants from Mitsubishi Tanabe Pharma, AbbVie, EA Pharma, and Mochida Pharmaceutical.