Takeda Pharmaceutical Company

Motohashi T., Shimada M., Tokunaga H., Kuwahara Y., Kuwabara H., Kato A., Tabata T.

Shikamura M., Takayama A., Yokogawa K., Kawakami K.

AbstractAimsWe aimed to investigate the temporal risk patterns of severe hypovolemia induced by sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus.Materials and MethodsWe conducted a self‐controlled case series using claims data from Japan. Patients who were prescribed SGLT2i for treating type 2 diabetes mellitus and experienced severe hypovolemia were enrolled. The primary analysis evaluated the adjusted incidence rate ratios (IRRs) of exposure risk periods (Days 1 to 30, Days 31 to 90, Days 91 to 180 and Days ≥181) with their corresponding 95% confidence intervals (CIs), calculated using a multivariable conditional Poisson regression model, relative to that of the unexposed control period.ResultsA total of 1200 new users of SGLT2i with 1334 severe hypovolemia events were included. The median follow‐up and treatment periods were 3.66 and 2.53 years, respectively. The cohort was predominantly male (78.4%) with a median age of 54.1 years. A higher risk of severe hypovolemia associated with SGLT2i was observed particularly in the first 30 days (adjusted IRR 7.39, 95% CI 6.09–8.96) of treatment initiation. Secondary analyses highlighted the first 22 to 28 days (adjusted IRR 15.24, 95% CI 11.92–19.48) of treatment as the highest risk period for severe hypovolemia.ConclusionsSGLT2i use in patients with type 2 diabetes mellitus was associated with a higher risk of severe hypovolemia, particularly within the first 30 days of treatment initiation, with the highest risk observed during 22 to 28 days.

Hongo F., Nakai Y., Nozawa M., Kato T., Kamikawa S., Tamada S., Yamada K., Soeda J., Tsubouchi R., Osaka T., Uemura H.

535 Background: Bone metastasis negatively impacts patients with advanced renal cell carcinoma (aRCC), leading to poor prognosis and quality of life. Some tyrosine kinase inhibitors, including cabozantinib, have been used as standard care for aRCC. However, there have been no reports demonstrating the effects of cabozantinib on bone metastasis. Here, we report the clinical effects of cabozantinib on bone metastasis in patients with aRCC. Methods: Patients with aRCC who had at least one measurable bone target lesion were enrolled. Patients received cabozantinib 60 mg once daily until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) of bone target lesions based on independent review committee (IRC) assessment using the MD Anderson Cancer Center (MDA) criteria, which are the response criteria specific to bone metastases. Key secondary endpoints included disease control rate (DCR), bone metastasis-free survival (BMFS), progression-free survival (PFS), overall survival (OS), frequency of symptomatic skeletal events (SSE) and safety. Results: In total, 31 patients were enrolled, with a median age of 70.0 years, and most patients (77.4%) had a history of systemic treatments for aRCC. All patients had bone metastasis. The ORR of bone target lesions by IRC-assessed MDA criteria was 6.5% (90% CI: 1.2–18.9), with a disease control rate (DCR) of 90.3% (90% CI: 76.8–97.3). No progressive disease was observed. The median BMFS was not reached (95% CI: 11.5–NR). The median PFS and OS were 11.9 (95% CI: 5.7–NR) months and 24.9 (95% CI: 19.1–NR) months, respectively. Three patients (9.7%) experienced SSE. No new safety concerns were identified. Conclusions: Cabozantinib demonstrated favorable clinical effects on bone metastasis in patients with aRCC, as suggested by a high DCR. Our results may provide useful insights for selecting optimal treatments for the management of aRCC with bone metastasis. Clinical trial information: jRCTs031210220 .

Wei W., Lin J.

Appleman V.A., Matsuda A., Ganno M.L., Zhang D.M., Rosentrater E., Maldonado Lopez A.E., Porciuncula A., Hatten T., Christensen C.L., Merrigan S.A., Lee H.M., Lee M.Y., Wang C.I., Dong L., Huang J., et. al.

Abstract The tumor microenvironment (TME) in solid tumors contains myeloid cells that modulate local immune activity. STING signaling activation in these myeloid cells enhances local type I interferon (IFN) production, inducing an innate immune response that mobilizes adaptive immunity and reprograms immunosuppressive myeloid populations to drive antitumor immunity. Here, we generated TAK-500, an immune cell directed antibody drug conjugate (iADC), to deliver a STING agonist to CCR2+ human cells and drive enhanced antitumor activity relative to non-targeted STING agonists. Preclinically, TAK-500 triggered dose-dependent innate immune activation in vitro. In addition, a murine TAK-500 iADC surrogate enhanced innate and adaptive immune responses both in vitro and in murine tumor models. Spatially resolved analysis of CCR2 and immune cell markers in the TME of >1,000 primary human tumors showed the CCR2 protein was predominantly expressed in intratumoral myeloid cells. Collectively, these data highlight the clinical potential of delivering a STING agonist to CCR2+ cells.

Li H., Kopetz S., Yin Y., Peng J., Keenan H.

64 Background: There are limited real-world data describing 3L and 4L treatments for pts with mCRC. However, the landscape is evolving with new options becoming available, including fruquintinib, a highly selective oral inhibitor of all 3 VEGF receptors, approved by the US FDA in November 2023. This study aimed to understand pt characteristics and real-world treatment patterns in 3L and 4L to characterize the standard of care, adherence to guidelines, and identify unmet needs among pts with mCRC in the US, prior to recent changes in the landscape. Methods: A retrospective study of adults with mCRC who had received ≥3L of therapy between 1/1/2018 and 3/31/2023 in the US-based Flatiron electronic health records database. In two cohorts, defined by initiating 3L and 4L systemic treatment, pt demographics, clinical characteristics, and treatment by line of therapy were summarized. Results: Overall, 5401 pts were included in the 3L cohort and 2868 pts in the 4L cohort: median age at baseline was 63 and 62 years (yrs), 56% and 56% were male, 43% and 43% had a KRAS variant, and 46% and 49% had liver metastasis, respectively. 96% of pts in the 3L cohort received standard chemotherapy (CT) +/- targeted therapy as 1L treatment (55% CT + anti-vascular endothelial growth factor [VEGF] therapy; 34% CT only; 7% CT + anti-epidermal growth factor receptor [EGFR] therapy). In 2L, 87% of pts had standard CT-containing regimens (53% CT + anti-VEGF therapy; 19% CT alone; 15% CT + anti-EGFR therapy). A similar treatment history was observed for the 4L cohort. Commonly used 3L regimens in the 3L cohort were trifluridine/tipiracil (TAS-102; 11%), regorafenib (rego; 10%), and standard CT-containing regimens (54%; including: 12% FOLFIRI + bevacizumab [bev], 7% FOLFOX + bev, 4% FOLFIRI, 3% FOLFOX, and 15% standard CT + anti-EGFR therapy). Approximately 47% (n=2513) of pts did not receive subsequent treatments after 3L. In the 4L cohort, use of TAS-102 (16%) and rego (15%) increased slightly in 4L, accompanied with a moderate decrease in CT-containing regimens (42%; including 6% FOLFOX + bev, 5% FOLFIRI + bev, 3% FOLFOX, 3% FOLFIRI, and 12% standard CT + anti-EGFR therapy). Approximately 4% of pts in the 3L and 4L cohorts received TAS-102 + bev in 3L and 4L, respectively. Pts receiving standard CT-containing regimens were slightly younger (<65 yrs: 3L 57%, 4L 58%) and had better Eastern Cooperative Oncology Group performance status (ECOG PS; 0-1: 3L 77%, 4L 77%) vs pts receiving TAS-102 (<65 yrs: 3L 54%, 4L 58%; ECOG PS 0-1: 3L 70%, 4L 68%) or rego (<65 yrs: 3L 50%, 4L 53%; ECOG PS 0-1: 3L 68%, 4L 70%). Conclusions: Characterization of treatment patterns in US pts from 1/2018 to 3/2023 showed that standard CT +/- targeted therapy was used frequently in 3L and 4L, demonstrating an unmet need for additional therapies. Approval of novel treatments, such as fruquintinib, may help to address this need.

Kagawa Y., Osaka T., Imamura T., Kuwabara H.

76 Background: The development of later-line drugs for metastatic colorectal cancer (mCRC) has expanded treatment options for systemic chemotherapy in patients with mCRC. However, few studies have investigated patients who received later-line treatment in a real-world setting, and available information on treatment sequences and transition rates from early- to later-line treatments is limited. Methods: This was a retrospective study using hospital administrative data collected by MDV (Medical Data Vision, Tokyo, Japan) from April 2008 through February 2023 in Japan. Treatment regimens were derived from standard treatments recommended in the Japanese guidelines. The study population was determined using an algorithm from a similar study previously conducted in Japan. Our analysis focused on patients who started CRC surgery or 1 st -line treatment after January 2017 to reflect recent late-line real-world practice. Transition rates from 1 st - to 5 th -line treatment were calculated, and treatment sequences were summarized using a Sankey diagram. Logistic regression was performed to identify the factors associated with the transition from 2 nd - to 3 rd -line treatment. Results: A total of 722,005 patients with a CRC diagnosis record were identified in the MDV database. Of these, 26,456 patients were included in the study population. The median age was 69 years and 61.4% of patients were male. The rates of transition to subsequent lines from 1 st to 5 th line ranged from 65.7% to 70.4% (1 st to 2 nd 68.3%; 2 nd to 3 rd 70.4%; 3 rd to 4 th 69.9%; 4 th to 5 th 65.7%). Among 8528 patients who received 2 nd -line treatment, ~70% of patients (6006) continued 3 rd -line treatment, and 30% of patients (2522) received best supportive care. Comparing these 2 patient groups, younger age (<65 years, OR: 1.50, 95%CI: 1.35-1.67; p<0.001) and longer treatment durations of 1 st (≥180 days, OR: 1.26, 95%CI: 1.14-1.39; p<0.001) and 2 nd (≥120 days, OR: 1.67, 95%CI: 1.52-1.84; p<0.001) lines were significant factors for 3 rd -line treatment continuation. Prior therapy with oxaliplatin or irinotecan plus molecular targeted drugs was also associated with a higher likelihood of proceeding to 3 rd -line treatment (OR: 1.42, 95%CI: 1.28-1.58; p<0.001). Conclusions: In this study, ~70% of patients were able to transition to subsequent lines at the time of each line transition. However, 30% of patients were unable to continue treatment in real-world practice. To increase treatment continuation rates and maintain patient quality of life, new treatment options and further research are necessary to meet patients’ treatment needs, especially in the later-line treatment setting where unfavorable effects from previous treatments are accumulated.

Ghezzi B., Valencia C., Dias de Oliveira R., Tsuha D., Lucena Júnior W., Di Pasquale A., Mc Namara M., Senra J., Abud D., Croda J.

Background/Objectives: Takeda’s tetravalent dengue vaccine TAK-003 has been approved by the Brazilian regulatory agency ANVISA for dengue disease prevention in individuals aged 4 to 60 years. Dourados, in the state of Mato Grosso do Sul, became the world’s first city to implement a mass vaccination campaign targeting approximately 120,000 individuals. An ongoing collaborative, observational, population-based study using national surveillance and vaccination data was planned to measure the impact of the vaccine on the reduction in dengue incidence. Methods: In this manuscript, the study’s methodology, including its programmatic steps and public health relevance, is described. A collaborative assessment with multidisciplinary researchers in Brazil was conducted to identify key programmatic areas for the successful implementation of the study. These areas included feasibility and site selection assessment, methodology selection, vaccination program implementation, and public health importance. Results/Conclusions: Identification of the public health problem and understanding the disease burden, local healthcare infrastructure, and strategic partnerships were critical for a robust feasibility assessment. One of the feasibility criteria identified was the ability of the Dourados Municipal Health Secretary and the principal investigator to conduct an active vaccination campaign, utilizing extramural activities and diverse communication channels to increase vaccine acceptance and coverage. The selection of analytical methods, such as time series analysis, was dependent on the national and local structures of the databases and data availability.

Vali Y., van Dijk A., Lee J., Boursier J., Ratziu V., Yunis C., Schattenberg J.M., Valenti L., Gomez M.R., Schuppan D., Petta S., Allison M., Hartman M.L., Porthan K., Dufour J., et. al.

ABSTRACTBackground and AimsThe performance of non‐invasive liver tests (NITs) is known to vary across settings and subgroups. We systematically evaluated whether the performance of three NITs in detecting advanced fibrosis in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD) varies with age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM) status or liver enzymes.MethodsData from 586 adult LITMUS Metacohort participants with histologically characterised MASLD were included. The diagnostic performance of the Fibrosis‐4 Index (FIB‐4), enhanced liver fibrosis (ELF) and vibration‐controlled transient elastography liver stiffness measurement (VCTE LSM) was evaluated. Performance was expressed as the area under the receiver operating characteristics curve (AUC). Thresholds for detecting advanced fibrosis (≥F3) were calculated for each NIT for fixed (high) sensitivity, specificity and predictive values.ResultsDifferences in AUC between all subgroups were small and statistically not significant, indicating comparable performance in detecting ≥F3, irrespective of these clinical factors. However, different thresholds were needed to achieve the same level of accuracy with each test. For example, for a fixed sensitivity and specificity, the thresholds for all three NITs were higher in patients with T2DM. Effects for sex, age and liver enzymes were less pronounced.ConclusionsPerformance of the selected NITs in detecting advanced liver fibrosis does not vary substantially with clinical characteristics. However, different thresholds have to be selected to achieve the same sensitivity, specificity and predictive values in the respective subgroups. Large prospective studies are called for to study NIT accuracy considering multiple patient characteristics.

Liu G., Nyaw S.F., Mok T.S., Curcio H., Cortot A.B., Kam T.Y., Descourt R., Chik Y.K., Cheema P., Gwinnutt J.M., Churchill E.N., Nyborn J., Curran E., Savell A., Yin Y., et. al.

ABSTRACTBackgroundReal‐world data regarding patients with non‐small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.MethodsA chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423). The inclusion criteria were: ≥ 18 years old; diagnosis of stage IIIB‐IV NSCLC with EGFR ex20ins between January 1, 2017 and November 30, 2021; received mobocertinib. Data on demographics, clinical parameters, treatment patterns, mobocertinib exposure, real‐world outcomes, and adverse events (AEs) were collected. Results are also reported by Asian/Non‐Asian races.ResultsOverall, 105 patients were enrolled (median [IQR] age at initial diagnosis: 64.0 years [56, 71]; women: 62.9%). The most common first‐line of therapy (LoT) was chemotherapy; the most common second LoT was EGFR tyrosine kinase inhibitors. Most patients received mobocertinib during LoT two and three (74.3%); the maximum dose was 160 mg/day for 67.6% of the cohort (mean [SD] daily dose: 130.6 mg [36.68]). The median real‐world progression‐free survival (PFS) on mobocertinib was 4.76 months (95% CI: 3.98, 6.21). The overall response rate and disease control rate were 20.0% and 48.6%, respectively (median duration of response: 8.34 months [95% CI: 3.61, 9.49]). The median overall survival (OS) was 26.28 months (95% CI: 20.21, 36.44). Asian patients had numerically superior PFS and OS compared with non‐Asian patients. Regarding safety analysis, 73 patients (69.5%) experienced any AE. The most common AE was diarrhea (any grade) (52 patients; 49.5%).ConclusionsThese data illustrate the real‐world effectiveness of mobocertinib.

Wu L., Wang J., Wahed A.S.

ABSTRACTClinical trials are often designed based on limited information about effect sizes and precision parameters with risks of underpowered studies. This is more problematic for SMARTs where strategy effects are based on sequences of treatments. Sample size adjustment offers flexibility through re‐estimating sample size during the trial to ensure adequate power at the final analysis. While this adaptation is common for standard clinical trials, corresponding methods to perform sample size adjustment have not been adapted to SMARTs. In this paper, we propose a sample size adjustment procedure for SMARTs. Sample sizes are re‐calculated at the interim analysis based on the conditional power derived from a bivariate non‐central chi‐square distribution. We demonstrate through simulation studies that even with an underpowered initial sample size due to miss‐specified parameters at the design stage, the proposed method can maintain desirable power at the end of the study, and additional resources are only invested in trials that show promising conditional power at the interim analysis.

Chemmalil L., Kulkarni T., Raman M., Singh P., Qian Y., Chumsae C., McHugh K., Huang Z., Hodgman E., Borys M.C., Ding J., Li G., Leone A.

ABSTRACTThis study emphasizes the critical importance of closely monitoring and controlling the sialic acid content in therapeutic glycoproteins, including EPO, interferon‐γ, Orencia, Enbrel, and others, as the level of sialylation directly impacts their pharmacokinetics (PK), immunogenicity, potency, and overall clinical performance due to its influence on protein clearance via hepatic asialoglycoprotein receptors (ASGPR). The ASGPR recognizes and binds to glycoproteins exposed to terminal galactose or N‐acetylgalactosamine residues, leading to receptor‐mediated endocytosis. Recent studies have demonstrated that sialylation of O‐linked glycan plays a role in protecting against macrophage galactose lectin (MGL)‐mediated clearance. In addition to the impact on serum half‐life, sialylation can influence other clinical outcomes, including immunogenicity, potency, and cytotoxicity. Therefore, the level of sialic acid is a critical quality attribute (CQA), and monitoring and regulating sialylation has become a regulatory requirement to ensure desired clinical performance. To achieve consistent levels of sialic acid‐to‐protein ratio, the time of upstream harvest and conductivity of downstream wash buffers must be tightly regulated based on the sialic acid content. Therefore, the utilization of process analytical technology (PAT) tools for generating real‐time or near‐real‐time sialic acid content is a business‐critical requirement. This work demonstrates the utility of an integrated PAT system for near real‐time online sialic acid measurements. The system consists of a micro‐sequential injection analyzer (µSIA) interfaced with SegFlow and an ultra performance liquid chromatography (UPLC). The fully automated architecture exemplifies the execution of online sampling, automatic sample preparation, and subsequent online UPLC analysis. This carefully orchestrated PAT framework effectively supports the requirements of QbD‐driven continuous bioprocessing.

Vermeire S., Jones S., Velazco N., Agboton C., Wojtowicz A.M., Young L., Phillips R., Loftus- Jr. E.V., Danese S., D’Haens G.

Abstract Background Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderate to severe ulcerative colitis (UC) or Crohn’s disease (CD). The subcutaneous (SC) formulation of VDZ was evaluated during the Phase 3 VISIBLE 1 and 2 studies. We report the long-term efficacy among patients (pts) with UC or CD treated with VDZ SC in the VISIBLE open-label extension (OLE) study. Methods Pts with UC or CD in VISIBLE 1/2 could enrol in VISIBLE OLE (NCT02620046). Pts in VISIBLE 1/2 who completed 52 weeks(W) of treatment with VDZ or placebo (randomised completers) and pts without clinical response at W6 who responded at W14 (non-randomised responders) received VDZ SC 108mg every 2W (Q2W) in the OLE. Pts with worsening disease were escalated to QW dosing. Clinical remission (partial Mayo score ≤2, no subscore &gt;1 in UC; HBI score ≤4 in CD) up to W168 was assessed (pts with missing data or escalated to QW dosing were imputed as non-response, irrespective of clinical status). The number of pts who regained clinical response when escalated to QW dosing was also assessed. Results were summarized by prior VISIBLE 1/2 treatment groups. Results Data from 231 pts with UC and 344 pts with CD were included. In pts with UC, baseline OLE clinical remission rates were 55.0%, 91.3% and 77.1% among randomised completers (N=124) previously treated with placebo, VDZ SC and VDZ IV in VISIBLE 1, respectively. At W168, 40.0%, 56.5% and 62.9%, respectively, were in clinical remission on Q2W dosing. In non-randomised responders with UC (N=107), 57.0% were in clinical remission at baseline and 29.9% at W168 (Figure). In pts with CD, baseline OLE clinical remission rates were 60.3% and 62.0% among randomised completers (N=226) previously treated with placebo and VDZ SC in VISIBLE 2. At W168, 32.4% and 37.3% were in clinical remission on Q2W dosing. In non-randomised responders with CD (N=118), 57.6% were in clinical remission at baseline and 27.1% at W168 (Figure). In pts with UC escalated to QW dosing, 22.2% and 38.1% achieved clinical remission and response at W8 after transitioning to QW. Among pts with CD escalated to QW dosing, 38.6% and 53.5% achieved clinical remission and response by W8 after transitioning to QW. Higher rates of remission and response were noted in VDZ completers than non-randomised responders. No new long-term safety signals were noted with VDZ SC vs IV, except for injection site reactions. Conclusion The clinical benefit of VDZ SC was maintained long-term during VISIBLE OLE. A subset of pts who escalated to QW dosing regained response. Findings support VDZ SC as a treatment option for patients with UC or CD who require long-term maintenance therapy.

Jairath V., Zou G., Adsul S., Colombel J.F., D'Haens G.R., Freire M., Moran G.W., Sebastian S., Travis S., Vermeire S., Hanžel J., Ma C., Sedano R., Sheridan P., Arya N., et. al.

Abstract Background The VERDICT study is a continuing, randomised controlled trial (NCT04259138)1-3 with a goal of determining the optimal treatment target for patients with moderate to severe ulcerative colitis (UC) by comparing 3 groups: Group 1 (corticosteroid-free [CSF] symptomatic remission); Group 2 (CSF symptomatic remission + CSF endoscopic remission); Group 3 (CSF symptomatic remission + CSF endoscopic remission + CSF histologic remission, also termed as disease clearance). This interim analysis reports target achievement up to week 48. Methods Following a treatment algorithm related to baseline UC treatment, vedolizumab (VDZ) 300 mg was administered intravenously until assigned treatment target was reached at week 48. CSF symptomatic remission was defined as Mayo rectal bleeding subscore=0, CSF endoscopic remission was defined as Mayo endoscopic score [MES]≤1, and CSF histologic remission was defined as Geboes score&lt;2B.0. Patients reaching CSF remission are considered to maintain remission at future visits. Results As of 05SEP2024, 672 patients were enrolled with 185, 222, and 265 patients assigned to Groups 1, 2, and 3, respectively. Baseline age, disease duration, and proportion of patients with MES=3 were similar amongst groups. Concomitant corticosteroids were received by 43.2%, 40.1%, 50.6% of patients, respectively (median dose 25.5, 25.3, 23.8 mg) and baseline MES=3 was similar across all 3 groups (60.0%, 61.7%, 65.3%). Bionaïve patients comprised 71.9%, 77.5%, 83.4% of patients in Groups 1, 2, and 3, respectively. In patients with observed data and a week 32 visit, 80.7% (92/114), 63.0% (97/154), and 53.3% (113/212) achieved CSF remission at week 32. In patients with observed data and a week 48 visit, 90.3% (84/93), 77.3% (102/132), 67.2% (123/183) achieved CSF remission by week 48, with higher proportions in bionaïve (70.1%) compared to bio-exposed (50.0%) for Group 3 (Figure 1). In the intention-to-treat population, 49.7%, 43.7%, and 42.6% of patients, respectively, achieved CSF remission at week 32, with higher proportions in patients who were bionaïve (45.7%) compared to bio-exposed (27.3%) in Group 3. By week 48, 45.4% (84/185), 45.9% (102/222), and 46.4% (123/265) of patients achieved CSF remission, with higher proportions with bionaïve (49.8% [110/221]) versus bio-exposed (29.5% [13/44]) in Group 3. At time of analysis, 50.3%, 59.5%, 69.1% of randomised patients had completed the week 48 visit. Conclusion These interim week 48 results provide evidence of improvement from week 32 to 48 across all endpoints and continue to support the efficacy of VDZ in achieving the stringent endpoint of CSF disease clearance. 96-week follow-up for all patients in the trial will be complete March 2026. References 1Jairath V, Zou G, Wang Z, et al. Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial. BMJ Open Gastroenterol. 2024;11:e001218. Doi:10.1136/bmjgast-2023-001218 2Jairath V, Zou G, Adsul S, et al. DOP11 Disease clearance after 16 weeks of treatment with vedolizumab in patients with moderate to severe Ulcerative Colitis: An interim analysis from the VERDICT trial. J Crohns Colitis. 2024;18 (Suppl 1):i92-i93. Doi: 10.1093/ecco-jcc/jjad212.0051 3Jairath V, Zou G, Adsul S, et al. PP0556 Target achievement after 32 weeks of vedolizumab treatment in patients with moderate to severe ulcerative colitis: An interim analysis from the VERDICT trial. UEG Week 2024 Poster Presentations. United European Gastroenterol J. 2024;12:665-1360. Doi: 10.1002/ueg2.12615

Agboton C., Halmos T., Geddes A.

Abstract Background Data suggest limited use of advanced therapies (AT) in inflammatory bowel disease (IBD) despite the accumulating data for the benefits of early, broader AT use.1-3 We evaluated barriers to AT use in IBD using a multimodal approach. Methods Market research was conducted June-November 2023. Quantitative survey on prescribing trends amongst gastroenterologists (GEs) prescribing ATs was conducted to capture AT initiation drivers in Germany, Italy, UK and US; questions for this survey were identified in qualitative interviews. GEs cycling an average of 0-1 and ≥2 conventional therapies (CTs) before initiating AT were classified as low and high cyclers, respectively. The COM-B (Capability, Opportunity, Motivation and Behaviour) model was used for behavioural analysis.4 Results Qualitative analysis covered responses from 62 participants (28 patients [pts], 24 GEs, 7 nurses, 3 pt organisation representatives), and quantitative analysis – from 142 GEs (Germany, 30; Italy, 30; UK, 30; US, 52) currently prescribing ATs, with 559 pt report forms (ulcerative colitis [UC], 280; Crohn’s disease [CD], 279) collected. CT cycling was more prevalent in UC vs CD; AT treatment was less likely in pts with UC vs CD (Figure). Differences among GEs by geography were only partially explained by cost containment in highly regulated markets (eg, Italy, UK). High cycling variations were linked to behavioural and belief-driven factors as illustrated by the notable use (7-20%) of 5-aminosalicylates in CD despite the lack of clinical guideline support. In behavioural analysis, AT initiation barriers included a lack of awareness of AT value and prescribing approach of exhausting all CT options before initiating AT. Low vs high cyclers placed higher importance on patient preference (UC, +16%; CD, +19%) and peer recommendations (UC, +13%; CD, +20%). In UC, the belief of exhausting all CT options before initiating AT was more important for high vs low cyclers (+9%). Qualitative research showed that the lack of clear guidelines disproportionately impacted high cyclers as they had reduced academic interest and limited capacity as contributors. Physician-relevant AT initiation drivers were the perceived CT risks and the growing recognition of the AT clinical value and long-term impact on the quality of life. Pt-relevant drivers included improved AT awareness and the ability and confidence for pts to self-advocate. Conclusion Cost containment and guideline variations could partially explain the observed geographic variations in AT use. Within any given country, clinical beliefs play a determining role. In Europe, a tangible increase in AT vs CT share could be achieved by encouraging GEs to initiate AT in pts with poor prognostic factors as per guideline suggestions. References 1. Noor NM, Lee JC, Bond S, et al. Lancet Gastroenterol Hepatol 2024;9(5):415-427. 2. Gordon H, Minozzi S, Kopylov U, et al. J Crohns Colitis 2024;18(10):1531-1555. 3. Kumar A, Yassin N, Marley A, et al. Therap Adv Gastroenterol 2023;16:17562848231218615. 4. Michie S, van Stralen MM, West R. Implement Sci 2011;6:42.