Introduction

During and following the COVID-19 pandemic, there has been a major expansion of self-administered subcutaneous biologics for the management of inflammatory bowel disease. These agents are more difficult to monitor since patients do not need to attend the Biologics infusion unit and there is no audit trail to confirm administration of the drug at the scheduled time points.

Aims & Methods

Following a successful NHS D&I bid for funding, a pilot proof of concept project to assess the feasibility and uptake of a digital technology (Health Beacon Digital Sharps Box®) to record and monitor subcutaneous injectable pen use was implemented in 50 consecutive IBD patients who were being treated with subcutaneous infliximab (Remsima®), Adalimumab (Amgevita®) or Vedolizumab (Entyvio®), on a 2-weekly schedule. The Health Beacon ICMS is comprised of a Smart Sharps Bin, pre-programmed with a patient’s individual treatment schedule. The bin electronically captures each time a used injection is disposed of, to create a time-stamped record as a proxy for medication adherence. This is accompanied by Health Beacon’s Companion App and Care Team support. Patients were also sent electronic dose reminders if they failed to dispose of a scheduled injection within certain time periods. Adherence data from the HealthBeacon ICMS, as well as patient satisfaction, transmission reports of data to

Results

Of 50 patients invited to join the programme, 45 registered patients had complete record of 6 months follow up; 4 patients deactivated recruitment and 1 left the programme. 21 patients were on Vedolizumab, 18 on Adalimumab and 8 on Infliximab, all 2-weekly SC injection. 45% patients were in the 36-50year age group, with the remaining spread between 18-75 years. M: F=21:24. Of 418 scheduled drops, 360 were made, with overall adherence being 86%. On time adherence was 76%. The study showed that up to 24% pts on SC Biologics at home delay their scheduled drug administration. Patient satisfaction was high. Reasons for delay in administration included forgetting, being away from home and being busy. Reminders were acknowledged.

Conclusion

This is the first study to our knowledge exploring adherence to subcutaneous biologics at home for IBD. It showed that a digital injection monitoring and support system is useful and acceptable to track adherence. Of the patients involved in the study there is an overall adherence of 90%, with up to 24% patients delaying their scheduled administration. Further studies are needed to analyse patient behaviour and impact on disease course.

Disclosure

Anjan Dhar has been paid an honorarium as a Speaker for presenting this abstract the a Health Beacon Meeting

Introduction

Guselkumab (GUS) intravenous (IV) induction followed by subcutaneous (SC) maintenance with 200mg q4w or 100mg q8w was effective in the GALAXI 2 & 3 phase 3 treat-through studies of participants (pts) with moderately to severely active Crohn’s disease (CD), with similar efficacy between both maintenance doses in the overall study populations. Here, we evaluated the efficacy of maintenance doses in subgroups by baseline disease activity and severity and inflammatory burden at Week (Wk) 12 to determine if some pts may receive additional benefit from the higher maintenance dose.

Aims & Methods

Eligible pts had moderately to severely active CD (CDAI 220–450 and mean daily stool frequency score >3 or abdominal pain score >1), SES-CD ≥6 (≥4 for isolated ileal disease), and inadequate response or intolerance to oral corticosteroids, AZA, 6-MP, MTX, or biologics. Pts were randomly assigned to GUS 200mg IV at Wks 0, 4, and 8, followed by GUS SC 100mg q8w (N=286) or 200mg q4w (N=296). The studies also included placebo and ustekinumab arms, but this analysis focused on differences between GUS maintenance doses. Wk48 endpoints included clinical remission (CDAI <150) and endoscopic response (≥50% improvement in SES-CD or SES-CD ≤2). Analyses of subgroups by baseline disease activity (CDAI >300 or SES-CD >12), and inflammatory burden (CRP >5) or endoscopic response at Wk 12 were prespecified but not multiplicity controlled.

Results

In the pooled GALAXI 2 & 3 dataset, pts with baseline high disease activity (CDAI >300 or SES-CD >12) had numerically greater clinical and endoscopic outcomes at Wk 48 with 200mg q4w compared with 100mg q8w. Pts with baseline CDAI >300 had numerically greater percentages of clinical remission (200mg: 68.0% [83/122] vs 100mg: 55.1% [65/118], respectively) and endoscopic response (52.5% [64/122] vs 44.1% [52/118]) at Wk 48. Pts with baseline SES-CD >12 also had numerically greater percentages of these outcomes (clinical remission: 77.0% [94/122] vs 65.1% [82/126] and endoscopic response 67.2% [82/122] vs 58.7% [74/126]). Pts with baseline CDAI ≤300 or SES-CD ≤12 had similar Wk 48 outcomes for both maintenance doses. Pts with greater inflammatory burden (CRP >5mg/L) at Wk 12 or who were not in endoscopic response at Wk 12 also had numerically greater clinical and endoscopic outcomes at Wk 48 with 200mg compared with 100mg (Table). Pts with CRP ≤5mg/L or who were in endoscopic response at Wk 12 had similar clinical and endoscopic outcomes for both maintenance doses. Results for individual GALAXI 2 & 3 studies generally trended in the same direction for all subgroups.

Conclusion

Pts with high clinical or endoscopic disease severity at baseline, greater inflammatory burden after induction, or who had not achieved endoscopic response after induction showed greater clinical and endoscopic outcomes at Wk 48 with GUS 200mg SC q4w compared with 100mg SC q8w.

Disclosure

AA: AbbVie, Bristol Myers Squibb/Celgene, DiaSorin, Eli Lilly, Gilead, IBD Horizons, Johnson & Johnson, Pfizer, Takeda, and TLL Pharmaceuticals
TH: grants from AbbVie GK, Boston Scientific Corporation, EA Pharma Co. Ltd., JIMRO Co. Ltd., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Pfizer Inc., Takeda Pharmaceutical Co. Ltd., and Zeria Pharmaceutical Co. Ltd.; consulting fees from AbbVie GK, Abivax, Bristol Myers Squibb, EA Pharma Co. Ltd., Gilead Sciences, Janssen Pharmaceutical K.K., Lilly, Mitsubishi Tanabe Pharma Corporation, and Pfizer Inc.; lecture fees from AbbVie GK, EA Pharma Co. Ltd., Janssen Pharmaceutical K.K., JIMRO Co., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co. Ltd.
DTR: consulting/speaker fees/advisory board for AbbVie, Altrubio, Apex, Avalo, Bristol Myers Squibb, Buhlmann Diagnostics, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Johnson & Johnson, Lilly, Pfizer, Samsung Neurologica, and Takeda; Altrubio, Datos Health, and Iterative Health stock options; grants from Takeda; membership on Board of Directors of Cornerstones Health, Inc and Crohn’s & Colitis Foundation’s Board of Trustees.
NAT, RVR, JY, KYYW, and ZY: employees of and may own Johnson & Johnson stock.
WR: speaker for AbbVie, Celltrion, Ferring, Johnson & Johnson, Galapagos Medice, MSD, Roche, Pfizer, Sobi, Takeda; consultant for AbbVie, Amgen, AOP Orphan, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celltrion, Eli Lilly, Galapagos, Gilead, Index Pharma, Johnson & Johnson, Medahead, Microbiotica, Pfizer, Takeda; advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, Johnson & Johnson, Pfizer; funding from AbbVie, Johnson & Johnson, Sandoz, Sanofi, Takeda.
BES: consulting fees from AbbVie, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Celltrion, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microba, Mirador Therapeutics, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Sorriso Pharmaceuticals, Spyre Therapeutics, Sun Pharma, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences, and Vividion Therapeutics; consulting /speaking fees from Abivax; consulting/speaking fees/other support from Lilly; research grants/consulting/speaking fees/other support from Bristol Myers Squibb, Johnson & Johnson, Pfizer, and Takeda; stock/options from Ventyx Biopharma.
SD: consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB, and Vifor; lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
RP: consulting fees from Abbivax, Abbott, AbbVie, Alimentiv, Amgen, AnaptsyBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Johnson & Johnson, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Spyre Therapeutics, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Union Biopharma, Viatris, Ventyx, and UCB; speaker’s fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Johnson & Johnson, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals; Advisory Boards for AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Johnson & Johnson, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, and Ventyx.

Introduction

Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical response at Week(W) 12 and maintaining clinical remission through W52 in patients with moderately-to-severely active Crohn’s disease (CD) as shown in the phase 3 treat-through trial VIVID-1 (NCT03926130).¹ Here, we present analysis of maintenance outcomes through W52 for Patient-Reported Outcome (PRO) clinical responders and nonresponders at W12.

Aims & Methods

The analysis set includes patients randomized to mirikizumab at baseline, who did or did not achieve PRO clinical response at W12 after intravenous (IV) induction treatment (900 mg mirikizumab IV every 4 weeks [Q4W]) before entering subcutaneous (SC) maintenance treatment (300 mg mirikizumab SC Q4W). Descriptive statistics are used to summarize the data, applying nonresponder imputation for missing binary endpoints. As a treat-through study, no rerandomization was applied.

Results

From a total of 551 patients who entered SC maintenance treatment, baseline characteristics of age, duration of CD, and baseline Crohn’s Disease Activity Index (CDAI) were similar between W12 PRO responders (n=402, 73.0%) and W12 PRO nonresponders (n=149, 27.0%). PRO responders at W12 had a higher objective inflammatory burden at baseline (faecal calprotectin, c-reactive protein, and Simple Endoscopic Score-CD), whereas concomitant or prior medication usage was similar between the groups. For W12 PRO responders, SC mirikizumab treatment from W12 to W52 resulted in an increase in CDAI clinical remission from 52.2% to 65.4%, PRO clinical remission from 53.2% to 65.4%, and endoscopic response from 35.1% to 54.7%, respectively (Table 1). Among W12 PRO nonresponders, PRO response was achieved by 39.6% at W16, 45.6% at W20, 44.3% at W24, and 56.4% at W52 with continued mirikizumab SC treatment, while CDAI clinical remission and PRO clinical remission were achieved by 33.6% and 31.5% at W52, respectively. Endoscopic response increased from 30.2% at W12 to 40.3% at W52 among W12 PRO nonresponders (Table 1).

Conclusion

Subcutaneous mirikizumab maintenance treatment over 40 weeks leads to incremental and sustained improvements in rates of clinical and endoscopic response regardless of PRO clinical response status after induction. A substantial proportion of clinical nonresponders at W12 improved early during maintenance treatment suggesting continued treatment with mirikizumab can be beneficial and lead to long-term response.

References

1. Ferrante, Marc et al. Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study. Lancet. 2024;404(10470):2423-2436. doi:10.1016/S0140-6736(24)01762-8

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

Irritable bowel syndrome is one of the most common Disorders of gut-brain interaction, with diarrhea being the predominant subtype. At present, there are limited drugs for effective management of irritable bowel syndrome.
Compound glutamine entersoluble capsules are composed of traditional chinese medicine formulas Sijunzi Tang and L-glutamine. The Sijunzi Tang, which has been used in traditional complementary and alternative integrated medicine, has been used for the treatment of irritable bowel syndrome for many years. However, there is a lack of evidence from modern evidence-based medicine, its clinical efficacy and safety need to be confirmed. L-glutamine has the function of repairing damaged intestinal mucosa.

Aims & Methods

This study performed a multicenter randomized double-blind placebo-controlled withdrawal trial to explore the effectiveness and safety of compound glutamine entersoluble capsules in the treatment of diarrhea predominant irritable bowel syndrome.
The selected participants received the investigational drug for four weeks during the first single arm stage. The responding participants were randomly assigned to the compound glutamine entersoluble capsules and placebo groups in a 1:1 ratio for another 4 weeks.
The primary efficacy endpoint of the study was the response rate of both the improvement in abdominal pain and bowel movements after treatment in randomized controlled trial subjects (50% of the treatment course met the requirement of at least 30% improvement in abdominal pain severity (NRS pain score) and a reduction of at least 50% in bowel movement days for Bristol 6 or 7 types).

Results

A total of 558 subjects in 22 centers, of which 493 subjects were successfully screened and entered the placebo introduction period. During the placebo introduction period, there were a total of 493 subjects, of which 481 subjects were successfully rescreened and entered the single arm period. 437 subjects entered the randomized controlled trial period and were randomly divided into a treatment group of 217 subjects and a placebo group of 220 subjects.
For the primary efficacy endpoint, the number of response cases in the experimental group and placebo group were 114 (54.55%) and 89 (41.20%), respectively (P=0.0059). For secondary efficacy endpoints: (1) The number of improvements in NRS pain scores in the experimental group and placebo group were 138 (66.03%) and 107 (49.54%), respectively (P=0.0006); (2) The number of improved bowel movements in the experimental group and placebo group were 157 (75.12%) and 118 (54.63%), respectively (P<0.0001); (3) The median (quartile) relative baseline change of IBS-SSS scale in the experimental group was -47.00 (-97.00, -14.00) points; The median (quartile) relative baseline change in the placebo group was -17.00 (-63.00, 16.00) points, and there was a statistically significant difference between the two groups (P<0.0001); (4) The median (quartile) relative baseline change of IBS-QOL in the experimental group was -11.46 (-43.01, 0.00) points; The median (quartile) relative baseline change in the placebo group was -3.57 (-39.43,0.00) points (P=0.0007).
During the randomized controlled trial period, the incidence of all adverse events in the 217 subjects in the trial group was 18.89%, the placebo group was 22.27%, the incidence of TEAEs related to the drug in the trial group was 2.30%, and the placebo group was 3.18%.

Conclusion

Compound glutamine entersoluble capsule can effectively improve the clinical symptoms of diarrhea predominant irritable bowel syndrome with a satisfactory safety.