Introduction

Pancreatic cancer has remained one of the most serious malignancies and is still a leading cause of cancer-related deaths worldwide. Great attention has been paid to the relationship between diabetes mellitus and pancreatic cancer. At the time of diagnosis of pancreatic cancer, impaired glucose metabolism has been reported to be present in variable rates according to particular studies (ref.).

Aims & Methods

Aims: The aim of our study was to analyse mutual association of pancreatic cancer and diabetes mellitus in the whole population of the Czech Republic within a 5-year period.
Methods: Based on the individual population data from the Czech National Cancer Registry, the incidence of pancreatic cancer in 2017-2021 was estimated. Another data source, the National Registry of Reimbursed Health Services that collects data from health insurance companies, was used to estimate people recently diagnosed with diabetes mellitus. For the purpose of this study, diagnosis of new-onset of diabetes mellitus was defined as the time of the first prescription of any antidiabetic drug (subgroup of patients with prediabetes treated with metformin was included). Patients with diabetes treated with diet only were not included. Subsequently, people diagnosed with pancreatic cancer in 2021 were retrospectively followed up to see if they had been diagnosed with diabetes mellitus in the last 5 years (or earlier) before diagnosis of pancreatic cancer.

Results

There were 310,427 new cases of diabetes mellitus identified within the period 2017 - 2021. Over this period, an average of 2,448 people were diagnosed with pancreatic cancer per year (23.1 / 100,000 population). In 2021, 2,064 patients > 60 years were diagnosed with pancreatic cancer. New onset of diabetes mellitus was recorded in 12.2% three years before the diagnosis of pancreatic cancer and four or five years before this diagnosis in another 5.2%. If we focus only on the 60-74 age group, the proportion was 13.8% and 5.8 %, respectively. Mutual association of diabetes mellitus and pancreatic cancer is displayed in the Table 1.

Table 1
Mutual association of diabetes mellitus and pancreatic cancer within the period 2017-2021

Conclusion

Incidence of pancreatic cancer in the Czech Republic belongs to the highest ones in Europe. New-onset of diabetes mellitus precedes the diagnosis of pancreatic cancer in nearly 20 % of cases within a 5-year period. These findings lead to considerations of the introduction of an early detection programme for pancreatic cancer in the Czech Republic based on new-onset of diabetes mellitus and possible other risk factors.

References

Cancers (Basel) 2023; 15(14): 3669

Introduction

Mirikizumab (miri), an anti-IL-23p19 antibody, has shown efficacy and safety in treatment of patients (pts) with moderately-to-severely active Crohn's disease (CD) up to Week 52 (W52) in a Phase 2 study (NCT02891226). We further assessed efficacy and safety, extending to W104.

Aims & Methods

At baseline, pts (N=191) were randomized 2:1:1:2 allocation across 4 treatment arms (1000, 600, 200mg miri and placebo (PBO), intravenously (IV) every 4 weeks (Q4W) at W0, W4, and W8). Pts who received miri and achieved ≥1 point improvement in Simple Endoscopic Score for Crohn’s Disease (SES-CD) at W12 were rerandomized 1:1 into double-blind maintenance to either continue IV treatment assignment Q4W (IV-C; N=41) or to 300mg miri subcutaneous (SC) Q4W (IV-SC; N=46) up to W52. W12 endoscopic non-improvers and pts receiving PBO during induction received IV 1000mg miri Q4W from W12-W52. Subjects reported to experience clinical benefit received 300 mg SC from W52 to W104. For analysis purposes, all IV and SC arms were pooled. The clinical and symptom endpoints [Crohn’s Disease Activity Index (CDAI) remission (CDAI Total Score <150) and patient-reported outcomes (PRO) remission (defined as SF ≤2.5 and AP ≤1 and no worse than baseline)] were evaluated among endoscopic improvers at W12 who were rerandomized into maintenance and went onto the extension period (W52-W104) (Table 1). Results were summarized by descriptive statistics with non-responder imputation (NRI).

Results

Of the 127 pts randomized to miri for induction, 68.5% (87/127) achieved endoscopic improvement at W12 and were rerandomized into maintenance. Of the W12 endoscopic improvers, 74 finished W52 maintenance and entered the extension period (W52 - W104) where 68 went on to complete treatment through W104. Among the W12 miri induction endoscopic improvers, CDAI remission rates were 39.0% (16/41) (IV-C) and 56.5% (26/46) (SC) and PRO remission rates were 46.3% (19/41) (IV-C) and 45.7% (21/46) (SC) at W52. One year later, (W104), CDAI remission rates were 66.7% (22/33) (IV-C) and 61.0% (25/41) (SC) and PRO remission rates were 63.6% (21/33) (IV-C) and 46.3% (19/41) (SC). Of the 74 endoscopic improvers who finished W52 maintenance, 6 discontinued between W52 to W104 (1 due to adverse events (AEs), 2 due to lack of efficacy, 1 due to lost to follow-up, and 2 due to withdrawal by subject). Among endoscopic improvers at W12, 4 pts were hospitalized due to CD in the SC group (2 from W12-W52 and 2 from W52-W104) as reported in Table 1. In all pts who received any miri treatment from W52 to W104 (endoscopic improvers, non-improvers, and PBO treated pts), 79.4% (108/136) experienced ≥ 1 treatment-emergent AEs.

Table 1. Week 52 and Week 104 Efficacy and Safety Results in Week 12 endoscopic improvers.

Conclusion

Miri demonstrated durable effectiveness among pts with moderately-to-severely active CD who showed early endoscopic improvement with continued miri dosing up to W104, and with no unexpected safety events. CDAI and PRO remission were sustained through W104, with no differences observed in pts who received either IV-C and SC miri treatments during maintenance and continued into the extension period.

Disclosure

Arthur Kaser: Scientific advisor to AstraZeneca, Janssen J&J, Pfizer, Novartis, Boehringer Ingelheim, Ferring, GlaxoSmithKline, Imhotex, Pandion, Merck, MiroBio, Applied Molecular Transport, Eli Lilly, Glenmark, Galapagos
Bruce E Sands: Received fees for consulting and speaking from Abivax, Bristol Myers Squibb, Janssen, Lilly Pfizer, and Takeda; for consulting from AbbVie; Adiso Therapeutics; Alimentiv; Amgen; Arena Pharmaceuticals; Artizan Biosciences; Artugen Therapeutics; AstraZeneca; Bacainn Therapeutics; Boehringer-Ingelheim; Boston Pharmaceuticals; Calibr; Celltrion Healthcare; ClostraBio; Cytoki Pharma; Connect Biopharma; Entera; Evommune; Fresenius Kabi; Galapagos; Genentech; Gilead Sciences; GlaxoSmithKline; Gossamer Bio; Imhotex; Immunic; Index Pharmaceuticals; Inotrem; Innovation Therapeutics; Ironwood Pharmaceuticals; Kaleido; Kallyope; MiroBio; Morphic Therapeutics; MRM Health; OSE Immunotherapeutics; Progenity; Prometheus Biosciences; Protagonist Therapeutics; Q32 Bio; Redhill Biopharma; Sun Pharma; Surrozen; Synlogic; Target RWE; Teva; Theravance Biopharma; TLL Pharmaceutical; USWM Enterprises; VielaBio: VTA Labs; and personal fees and stock options for consulting from Ventyx Biosciences.
Laurent Peyrin-Biroulet: Personal fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boerhinger Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Inotrem, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, and Theravance; grants from Abbvie, MSD, and Takeda; and stock options from CTMA.
Vipul Jairath: Consulting/advisory board fees: AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso pharmaceuticals, Takeda, Teva, Topivert, Ventyx, Vividion; speaker’s fees: Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi
Monika Fischer: Advisor for Abbvie, Eli Lilly, BMS, Pfizer, Ferring, Seres, Speaker for Janssen and BMS, DSMB for Rebiotix/Ferring
Marijana Protic, Zhantao Lin, Rebecca Hozak, Hilde Carlier, and Emily Hon: employees and shareholders of Eli Lilly and Company.

Introduction

Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking agent, was approved in Europe and the USA for the treatment of moderate-to-severe Crohn’s disease (CD) in 2014. Real-world evidence is essential for understanding the effectiveness and benefit–risk profile of VDZ for CD outside clinical trial settings. A systematic literature review and meta-analysis published in 2018 confirmed the real-world effectiveness and positive benefit–risk profile of VDZ treatment for up to 12 months in patients with inflammatory bowel disease.¹ However, there are limited real-world evidence on the long-term (> 12 months) effectiveness of VDZ in patients with CD.

Aims & Methods

A systematic literature review was performed using MEDLINE, MEDLINE In-Process, Embase, Cochrane Library, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform to identify relevant studies published from May 2014 to July 2022. In addition, if the congress abstracts were not indexed in Embase, key congresses from 2015 to July 2022 were hand-searched. Data from adults (aged ≥ 18 years) with CD treated with VDZ in a real-world setting were extracted for meta-analysis. Depending on data availability, the analysis was conducted using the DerSimonian-Laird random-effects model to obtain weighted mean rates (percentage of patients) and the corresponding 95% confidence interval (CI) for each outcome of interest, as per the 2018 meta-analysis.¹ The aims of the current analysis were to evaluate the rates of treatment persistence at 12 and 24 months and mucosal healing at 12 months (overall and stratified by biologic-naïve versus biologic-experienced patients) to address the paucity of long-term data available on these outcomes.

Results

Overall, data from 78 studies of 30 158 patients with CD had at least one outcome of interest for analysis. Using the reported number of patients as the weight, the baseline weighted mean age was 39.3 years (standard error [SE] 2.7; 15 studies), weighted mean disease duration was 12.5 years (SE 0.5; 8 studies), weighted mean CD activity index score was 177 (SE 4.3; 3 studies), and weighted mean Harvey-Bradshaw index score was 7.9 (SE 0.7; 5 studies). In the 32 and 13 studies that assessed treatment persistence at 12 and 24 months, respectively, the rates of treatment persistence were 62.8% (95% CI 56.6–68.9) and 54.9% (95% CI 44.3–65.4), and were higher in biologic-naïve patients than biologic-experienced patients at both time points (Table). The rate of mucosal healing at 12 months (assessed in 20 studies) was 38.4% (95% CI 30.2–46.5) and was higher in biologic-naïve patients than biologic-experienced patients at both time points (Table).

Conclusion

This meta-analysis of real-world studies of VDZ demonstrated high rates of robust, long-term treatment persistence and mucosal healing in patients with CD, particularly in biologic-naïve versus biologic-experienced patients. Over a third of patients achieved mucosal healing at 12 months, confirming the effectiveness of VDZ for achieving this important treatment outcome.

References

1. Schreiber S et al. J Gastroenterol 2018;53:1048–64.

Disclosure

This study was funded by Takeda Pharmaceuticals International AG. Medical writing services were provided by Matthew Reynolds, of Oxford PharmaGenesis, and funded by Takeda Pharmaceuticals International AG.
SS: Personal fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Dr. Falk Pharma, Fresenius, Galapagos/Gilead, Hikma, I-Mab, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, ProventionBio, Takeda and Theravance Biopharma.
PB: Employee and stockholder of Takeda Pharmaceuticals International AG, Zurich, Switzerland.
RJB: Employee of PHMR Ltd., who received funding for this study from Takeda Pharmaceuticals International AG.
MN: Employee and stockholder of Takeda Pharmaceuticals International AG, Zurich, Switzerland.
SW: Employee and stockholder of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
AA Advisory board/lecture fees from AbbVie, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda.

Introduction

The efficacy and safety of upadacitinib (UPA), an oral, reversible Janus kinase (JAK) inhibitor approved for the treatment of moderately to severely active Crohn’s disease (CD),^1.2 has been demonstrated in two phase 3 induction studies (U-EXCEL, NCT03345849³; U-EXCEED, NCT03345836⁴) and a phase 3 maintenance study (U-ENDURE, NCT03345823⁵). An association between shorter disease duration and improved outcomes has been shown in post hoc analyses of clinical trial data with other advanced CD therapies.^6,7 We therefore conducted a post hoc analysis of data from these phase 3 UPA studies to assess the potential impact of CD duration on UPA efficacy.

Aims & Methods

Patients in the induction studies were randomized 2:1 to receive UPA 45 mg (UPA45) or placebo (PBO) once daily for 12 weeks.^2,3 Patients achieving clinical response per stool frequency and/or abdominal pain score (SF/APS) criteria were re-randomized 1:1:1 in the maintenance study to UPA 30 mg (UPA30), UPA 15 mg (UPA15), or PBO once-daily for 52 weeks.⁴ Efficacy was evaluated in patient subgroups stratified by CD duration at baseline (< 2 years, 2–5 years, >5–10 years, and >10 years). Endpoints evaluated at week 12 (induction) and week 52 (maintenance) included achievement of clinical remission (per average daily very soft/liquid SF/APS and per Crohn’s Disease Activity Index [CDAI]), normalization of fecal calprotectin and high-sensitivity C-reactive protein levels for patients with elevated baseline levels, endoscopic response, endoscopic remission, and mucosal healing.

Results

Baseline patient and disease characteristics were generally similar across CD duration subgroups during induction (N = 1021). UPA45 demonstrated nominally greater improvement vs PBO in efficacy endpoints across most CD duration subgroups at week 12 (Table). UPA45-treated patients with a shorter disease duration had numerically greater endoscopic improvement vs patients with longer disease duration, and nominally greater endoscopic improvement vs patients receiving PBO at week 12 (Table). Further, the clinical remission rate per CDAI at week 12 was numerically higher with UPA45 vs PBO in patients with CD duration < 2 years, and was nominally higher vs PBO in other CD duration subgroups (Table). Consistent with induction outcomes, UPA30 and UPA15 demonstrated nominally or numerically greater improvement in efficacy endpoints vs PBO regardless of disease duration at week 52 (Table); there was also a general trend towards greater improvements in efficacy outcomes in patients with a shorter disease duration.
​Table. Efficacy Outcomes by Baseline CD Duration During Induction and Maintenance Studies

Conclusion

Regardless of disease duration, UPA demonstrated positive clinical and endoscopic outcomes in patients with moderately to severely active CD. Achievement of endoscopic endpoints was numerically higher in patients with shorter vs longer duration of CD, suggesting initiation of UPA earlier in the disease course may lead to better outcomes for patients.

References

1. RINVOQ. Summary of Product Characteristics. AbbVie Deutschland GmbH & Co. KG; 2023. Accessed 24 April 2023. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf
2. RINVOQ. Summary of Product Characteristics. AbbVie Inc.; 2023. Accessed 27 March 2023. https://www.medicines.org.uk/emc/product/12830/smpc.
3. Loftus E, et al. United European Gastroenterol J. 2022;10(S8):103.
4. Colombel J-F, et al. Gastroenterology. 2022;162(7):S-1394.
5. Panés J, et al. Am J Gastroenterol. 2022;117:S10.
6. Faleck DM, et al. Clin Gastroenterol Hepatol. 2019;17(12):2497–2505.
7. Peyrin-Biroulet L, et al. J Crohn's Colitis. 2022;16(Suppl 1):i045–i048.

Disclosure

RCU has served as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Janssen, Pfizer, and Takeda; received research support from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, and Pfizer; and is funded by a National Institutes of Health (NIH) K23 Career Development Award K23KD111995-01A1.
LP-B has received personal fees from AbbVie, Allergan, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Enterome, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Hikma, InDex Pharmaceuticals, Inotrem, Janssen, Lilly, MSD, Mylan, Nestle, Norgine, Oppilan Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Pharmacosmos, Roche, Samsung Bioepis, Sandoz, Sterna, Sublimity Therapeutics, Takeda, Theravance, Tillots, and Vifor; research grants from AbbVie, Fresenius Kabi, MSD, and Takeda; and stock options from CTMA.
JFC has received research grants from AbbVie, Janssen, and Takeda; payment for lectures from AbbVie, Amgen, Ferring, Shire, and Takeda; consulting fees from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enterome, Ferring, Genentech, Janssen, Medimmune, Merck, Novartis, Pfizer, Protagonist Therapeutics, Sandoz, Second Genome, Seres Therapeutics, Shire, Takeda, Theradiag, and Theravance; and holds stock options in Genfit and Intestinal Biotech Development.
EJL has received research grants from Janssen, Pfizer, and Takeda; educational grants from AbbVie, Janssen, MSD, and Takeda; speaker fees from AbbVie, Falk, Ferring, Hospira, Janssen, MSD, Pfizer, and Takeda; served on advisory boards for AbbVie, Arena, Celgene, Ferring, Galapagos, Gilead, Hospira, Janssen, MSD, Pfizer, and Takeda; and served as a consultant for AbbVie.
MF has received financial support for research from AbbVie, Amgen, Biogen, EG, Janssen, Pfizer, Takeda and Viatris; consultancy fees from AbbVie, Agomab Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, Medtronic, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, and Thermo Fisher Scientific; and speaker fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Falk, Ferring, Janssen-Cilag, Lamepro, MSD, Pfizer, Sandoz, Takeda, Truvion Healthcare and Viatris.
TM has received grants and honoraria from EA Pharma, AbbVie, Pfizer, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Nippon Kayaku Co., and Zeria Pharmaceutical Co; honoraria from Kyorin Pharmaceutical Co., JIMRO Co., Nichi-lko Pharmaceutical Co., and Takeda; and grants from Daiichi-Sankyo.
CD, APL, VPR, ED, SIA, and AG are employees or contractors of AbbVie, and may own AbbVie stock and/or stock options.
RP has received consultancy and/or speaking honoraria from Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB.
Funding
AbbVie Inc. funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and authors thank all the trial investigators and the patients who participated in this clinical trial. Medical writing support was provided by Tracy Wetter, PhD, and Akua Adu-Boahene, MD, MPH, of JB Ashtin, and funded by AbbVie.