Introduction

Ozanimod (OZA) is approved for patients with moderately to severely active ulcerative colitis (UC) based on results from the pivotal phase 3 True North (TN) trial.

Aims & Methods

This analysis evaluated the impact of disease duration at TN baseline (BL) on OZA efficacy during the TN induction period (IP). In the 10-week TN IP, patients were randomized to receive in a double-blind fashion either placebo (PBO) or OZA in Cohort 1 or open-label OZA in Cohort 2. All patients in Cohort 1 of the TN IP were included in this analysis and stratified by disease duration at TN BL; subgroups included patients with <2 years, 2 to <5 years, 5 to <10 years, or ≥10 years since UC diagnosis. Symptomatic remission and response were assessed through W10 within these subgroups using PBO-adjusted difference in proportions; treatment differences and P-values for comparisons between OZA and PBO were based on the Cochran-Mantel-Haenszel test, stratified by corticosteroid use at screening and prior anti–tumor necrosis factor (TNF) use. Clinical response and clinical remission at W10 were also analyzed. A stepwise logistic regression model was used to adjust for potential BL patient characteristic confounders.

Results

A total of 645 patients were included in Cohort 1 of the TN IP (PBO, N=216; OZA, N=429). At TN BL, 158 patients had a disease duration of <2 years (PBO, n=55; OZA, n=103), 178 had 2 to <5 years (PBO, n=64; OZA, n=114), 163 had 5 to <10 years (PBO, n=52; OZA, n=111), and 146 had ≥10 years (PBO, n=45; OZA, n=101). BL patient characteristics were generally similar in all subgroups of the OZA and PBO treatment arms. As expected, more patients with longer disease duration had prior exposure to biologic therapies. In Cohort 1, prior anti-TNF use and prior biologic use, except anti-TNF, was reported in 5.1% and 3.2% of patients, respectively, in the <2 years duration group, 32.6% and 19.7% in the 2 to <5 years group, 38.7% and 27.6% in the 5 to <10 years group, and 43.8% and 26.7% in the ≥10 years group. Patients with disease duration <2 years achieved greater symptomatic clinical response by W4 (P<0.001) compared to other subgroups, but differences were similar across other subgroups by W10; symptomatic remission rates were also generally similar across subgroups by W10. The proportions of patients achieving clinical remission and clinical response after 10 weeks of OZA treatment were comparable, regardless of TN BL disease duration (Table). Finally, a logistic regression model demonstrated that BL disease duration did not affect OZA efficacy.

Conclusion

OZA efficacy at the end of induction was not affected by duration of disease in patients with UC. These results suggest that OZA is an optimal oral therapeutic option for newly diagnosed patients and for those with long-standing UC disease.

Disclosure

Acknowledgment: This study was sponsored by Bristol Myers Squibb, Princeton, NJ, USA. Professional medical writing assistance was provided by Anny Wu, PharmD, and Julie Ko, PharmD, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb.
AH: consultant, advisory board member, or speaker for AbbVie, Atlantic, Bristol Myers Squibb, Celltrion, Dr. Falk Pharma, Ferring, Janssen, MSD, Napp Pharmaceuticals, Pfizer, Pharmacosmos, Shire, and Takeda; served on the Global Steering Committee for Genentech.
GD: served as an advisor for AbbVie, Agomab Therapeutics, Alimentiv, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Exeliom Biosciences, Ferring, Galapagos, GlaxoSmithKline, Immunic, Johnson & Johnson, Pfizer, Polpharma, ProciseDx, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Seres, Takeda, Tillotts, and Ventyx; received speaker fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos, Johnson & Johnson, Pfizer, Takeda, and Tillotts.
AW: received research grants or consulting fees from AbbVie, Bühlmann Laboratories, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Pfizer, Takeda, and Vifor.
SCG: declared no competing interests.
DJL: received consulting fees from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Fresenius Kabi, Janssen, Magellan Health, Palatin Technologies, Pfizer, Prometheus Laboratories, PSI, and Takeda; received research funding from AbbVie, Boehringer Ingelheim, Janssen, and Takeda; served on speaker bureaus for AbbVie and Janssen.
BLC: received consultancy or speaker fees from AbbVie, Emmes, Janssen, Takeda, and Target RWE; received support and/or funding from AbbVie, Bristol Myers Squibb, Celgene, Janssen, and Pfizer.
GL, MR, HW, MTO, and AJ: employees and/or shareholders of Bristol Myers Squibb.
GRL: received research support and/or funding from Celgene, Janssen, Ortho Biotech, Pfizer, Shire, Takeda, and UCB; received consultancy fees from AbbVie, American Regent, Cellceutix, Celgene, Eli Lilly, Endo, Ferring, Gilead, Janssen, Merck, Morphic Therapeutic, Ortho Biotech, Pfizer, Prometheus Laboratories, Romark, Salix/Valeant, Shire, Takeda, and UCB; received honoraria from American College of Gastroenterology, American Regent, Gastroenterology & Hepatology journal, Merck, Romark, Springer Science and Business Media, and UpToDate; received royalties from Professional Communications Inc. and SLACK Inc.

Introduction

The Revision of the Atlanta Classification (RAC) defines severe acute pancreatitis (AP) by the presence of persistent organ failure (OF), limited to respiratory, renal, or cardiovascular systems, this being associated with a high mortality rate. Whether gastrointestinal bleeding (GIB) and impaired mental status (IMS) should be considered as OF remains unclear. We aimed to assess the association of GIB and IMS with mortality and other outcomes.

Aims & Methods

We performed a retrospective analysis of a prospective database including 1,612 AP patients. GIB was defined as bleeding >500 mL. IMS was defined as a Glasgow score ≤14 at baseline. Multivariate logistic regression models were used to assess associations with mortality, controlling for comorbidity and RAC- defined OF. Two models were used: one including all OF (any duration), and another including only persistent OF.

Results

GIB occurred in 1.5% and IMS in 3% of patients. Both were associated with worse outcomes in bivariate analysis. In multivariate models, GIB was not independently associated with mortality. IMS was independently associated with mortality (aOR 4.0, 95% CI 1.2–13.4) only when adjusting for persistent OF, but not when adjusting for OF of any duration. Renal, respiratory or cardiovascular OF of any duration, as well as persistent OF, had an independent and very strong association with all the outcome variables including mortality, clearly differentiating them from GIB and IMS.

Conclusion

GIB and IMS are markers of disease severity but do not show a consistent independent association with mortality comparable to the current RAC definition of OF.

Introduction

Alcohol is a common cause of acute pancreatitis, and ongoing consumption increases the risk of recurrent episodes. There are no international guidelines to direct behavioural or pharmacological interventions to reduce recurrence of alcohol-associated acute pancreatitis (AAP). Studies exploring the role of addiction medicine in patients with AAP are limited.

Aims & Methods

This study describes the uptake and role of the Addiction Medicine Unit (AMU), a specialist consultative service, in patients admitted with AAP. We conducted a retrospective cohort study including all inpatients diagnosed with AAP at a large multisite tertiary health service in Melbourne, Australia between May 2022 to May 2024. Patient demographics, diagnosis of alcohol use disorder (AUD) and pharmacological and non-pharmacological interventions provided by the AMU were obtained from the patient’s medical records.

Results

A total of 231 patients with 314 admissions with AAP were identified. Most were males (77.9%) with a median age of 44 years (IQR 21), with median bedside index of severity in acute pancreatitis (BISAP) score of 1 (IQR 1). Of the patients, 35 (11.1%) had necrotising pancreatitis, 30 (9.6%) required admission to the intensive care unit (ICU), and 1 patient died from AAP. The prevalence of AUD was 82.3%. Referral to the AMU occurred in 56.7% of admissions, predominantly among those with AUD (87.6%). Patients referred to the AMU had a higher median number of standard drinks per week (70 standards, range 6-385 standards) compared to those who were not referred (49 standards, range 1-301 standards) (p=0.024). The AMU recommended outpatient services alone in 40.4%, both pharmacological and outpatient interventions in 37.6%, and medications alone in 21.9%. Outpatient services included either a service for community-based assessment and counselling (86.4%), residential rehabilitation programs and/or detox services (5.8%), follow up in the AMU outpatient clinic (3.9%) or a combination of these outpatient services (3.9%). There were 137 (43.6%) admissions in which patients were commenced on medications for AUD. Topiramate (42.6%), and naltrexone (42.6%) were the most prescribed pharmacological agents by the AMU, followed by baclofen (9.8%), acamprosate (4.1%) and disulfiram (0.8%). Over the 2-year period, 54 (23.4%) were readmitted with AAP. Most patients were not readmitted within 30 days of discharge (73.2%) however there were 33 (10.5%) patients readmitted for pancreatitis or pancreatitis-related complications including pain or infection, and 18 (5.7%) readmitted to hospital for non-pancreatitis related reasons. Patients who were older (median 49 years) were more likely to be readmitted with AAP compared to those who were younger (median age 43 years) across the study period (p=0.05). There were six patients re-admitted with AAP with their index admission deemed related to an alcoholic binge without suspected underlying AUD. Of these six patients, only two were referred and reviewed by the AMU, with the other four patients not referred.

Conclusion

Our study highlights the critical role of the AMU in managing AAP, particularly given the high prevalence of concurrent AUD in this population. Despite this, significant gaps remain in screening for AUD and initiating referrals, resulting in only half of AAP patients being referred. Considering the substantial morbidity and healthcare cost associated with alcohol, efforts to improve referral practices during index admissions may be key to reduce readmissions for AAP and improve patient outcomes.

Introduction

Depressive and anxiety symptoms may influence the severity of acute pancreatitis episodes; however, their impact, particularly in pancreatic units, remains poorly understood.

Aims & Methods

Our study aimed to identify risk factors associated with poorer psychological assessment scores in patients with acute and chronic pancreatitis (AP, CP) and their impact on clinical outcomes.
Patients admitted to a tertiary pancreatic unit were assessed for depressive and anxiety symptoms upon admission, with follow-ups every seven days during hospitalization. Psychological states were measured using the Hospital Anxiety and Depression Scale (HADS).

Results

Of the 1,397 admitted patients (median = 54, range = 17–97), 1,237 completed the questionnaire (42.98% female). At admission, 56.5% of patients had normal scores (0-7 points), 23.4% had borderline abnormal scores (8-10 points), and 20.3% had abnormal scores (11-21 points). The prevalence of abnormal cases at intervention, i.e. before intervention, was 20.15% in AP, 23.15% in early chronic pancreatitis (ECP), and 24.15% in acute-on-chronic pancreatitis (ACP). Borderline abnormal cases were observed in 22.25%, 24.15%, and 19.15% of cases, respectively. Abnormal cases varied by etiology: hypertriglyceridemia (13.9%), biliary (16.9%), alcohol-related (26.3%), and tumor-related pancreatitis (26.6%). The prevalence also differed by AP severity: mild AP (17.76%), moderate AP (23.94%), and severe AP (35.05%). Following psychological intervention, the number of patients with abnormal scores decreased (67.6%, 19.6%, and 12.8%, respectively).

Conclusion

Depressive and anxiety symptoms are common in patients with acute and chronic pancreatitis, with more severe AP already associated with worse psychological scores at admission. Psychological interventions are essential to improve clinical outcomes.

Introduction

Although we previously demonstrated that AAV8-hSPINK1 safely exhibited significant alleviation of chronic pancreatitis (CP) progression¹, the limited pancreas specificity of AAV8 leads to off-target expression of the transgenes. Additionally, the CMV promoter, as a ubiquitous promoter, lacks tissue preference, hindering its usage in AAV-mediated gene therapy for pancreatic diseases.

Aims & Methods

We aimed to construct a novel pancreas acini-specific promoter to restrict the ectopic expression of transgenes and further enhancing the precision of gene therapy for pancreatic diseases. By integrating human scRNA-seq database, the TiGER database, and our mouse RNA-seq data from Part II, we identified highly conserved genes that are richly expressed in pancreatic acini across species. Sequences surrounding the transcriptional start site (TSS, designated as +1) were selected as candidate compacted pancreas-specific promoters. We first validated transcriptional activity of the candidate promoters using dual-luciferase reporter assay. Subsequently, we packaged compacted promoters into AAV to drive ZsGreen gene expression and injected into mice. Pancreas and liver were collected and immunofluorescence, qRT-PCR, and Western blot were performed to characterised the efficiency and tissue selectivity of the candidate promoters. Finally, the synergistic effects of combining short enhancer fragments from human or rat amylase genes with the candidate promoters were assessed to enhance transcriptional activity.

Results

We selected the promoter sequences originated from hPRSS1 (408 bp), rCela1(-500/+8) (508 bp), rCela1(-205/+8) (213 bp), hSPINK1 (120 bp) as candidates. In vitro dual luciferase activity assays results indicated that the relative luciferase activities of hPRSS1 promoter and rCela1(-500/+8) promoter were 2.77±1.64 and 3.91±0.93, respectively (compared with CMV [100]), which were significantly higher than that of the empty vector group (0.199±0.20) (all P < 0.001). However, the rCela1(-205/+8) and hSPINK1 promoters exhibited no significant promoter activity. Compared to the CMV promoter, the ZsGreen expression levels driven by the hPRSS1 and rCela1(-500/+8) promoter were lower, whereas the pancreas-to-liver ZsGreen mRNA ratio demonstrated that both compacted promoters had pronounced pancreatic transduction preference, which elevated pancreatic-specific expression by 77.81- and 63.02-fold, respectively (all P < 0.001). We finally introduction of human amylase AMY2A (34 bp) and rat Amy2a3 (40 bp) enhancer into hPRSS1 and rCela1(-500/+8) promoters. The Amy2(rat)-hPRSS1 promoter markedly increased the pancreatic transduction efficiency by 8-fold, and was selected as the optimal compacted enhancer-promoter sequence.

Conclusion

The compact pancreatic acini-specific enhancer-promoter, Amy2(rat)-hPRSS1, dramatically improved the pancreas gene transfer efficiency in vivo and eliminating liver tropism, serving a promising tool for pancreas-specific gene therapy targeting exocrine pancreatic diseases, including acute pancreatitis, chronic pancreatitis, and precancerous lesions of pancreatic cancer.

References

1. Wang YC, Mao XT, Sun C, et al. Pancreas-directed AAV8-hSPINK1 gene therapy safely and effectively protects against pancreatitis in mice. Gut 2024;73:1142-1155.

Disclosure

All authors declare no conflicts of interest.

Introduction

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is widely recognized as the preferred diagnostic method for pancreatic lesions, achieving diagnostic accuracy rates between 78% and 95%. Rapid on-site evaluation (ROSE) improves adequacy rates but remains unavailable in many centers. In this context, we evaluated a simplified method, Visual On-Site Evaluation (VOSE), based on macroscopic evaluation of the biopsy sample, to predict histo-cytological adequacy without needing ROSE.
Primary aim: assess the accuracy of VOSE in predicting sample adequacy.
Secondary aims: evaluate the diagnostic yield of FNB and the potential reduction in unnecessary needle passes.

Aims & Methods

This prospective single-center study enrolled patients undergoing EUS-FNB for pancreatic lesions between January 2020 and February 2024.
VOSE parameters included the presence of a macroscopic visible core (MVC), number of specimens, and specimen length. Associations between VOSE findings and final histo-cytological adequacy were analyzed using Fisher’s exact test and Student’s t-test. A p-value < 0.05 was considered statistically significant. Study conducted at a university hospital center.

Results

Fifty-nine patients (57.6% male; mean age 67.9 ± 9.8 years) were included, contributing to a total of 59 pancreatic lesions. Across 218 passes performed, the overall sample adequacy rate was 91.5%.
Adequacy was significantly higher when using 22-G needles compared to 25-G needles (95.7% vs. 86.2%, p = 0.018). VOSE criteria (presence of MVC, multiple fragments, and long specimen) demonstrated a sensitivity of 52.3%, a specificity of 61.1%, and a positive predictive value (PPV) of 93.1% for predicting sample adequacy. Applying VOSE led to a 45% reduction in unnecessary additional passes.

Conclusion

EUS-FNB provides excellent diagnostic adequacy for pancreatic lesions, particularly with 22-G needles. The use of VOSE, a simple and reproducible macroscopic evaluation method, can reliably predict histo-cytological adequacy and substantially reduce the number of passes, offering a practical alternative in centers without ROSE availability.

References

1. El Chafic AH, Loren DE, Siddiqui AA. EUS-guided fine-needle biopsy of pancreatic masses: new tools, new techniques. Endosc Ultrasound. 2023;12(1):3-10.
2. Crinò SF, Larghi A, Bernardoni L, et al. EUS-guided fine-needle biopsy with or without ROSE for pancreatic masses: A multicenter randomized trial. Gastrointest Endosc. 2023;98(2):225-234.e3.
3. Bang JY, Hebert-Magee S, Navaneethan U, Hasan MK, Hawes R, Varadarajulu S. EUS-guided fine-needle biopsy of pancreatic masses: a meta-analysis comparing FNA and FNB. Gastrointest Endosc. 2022;95(5):893-905.e2.

Introduction

There is currently lack of published data on the use of ustekinumab (UST) in routine care setting in Greece. REASSURE study aimed to generate real-world evidence (RWE) on treatment persistence, and patient-reported outcomes (PROs) in patients with Crohn’s Disease (CD).

Aims & Methods

This was an observational, prospective study of adult (18-80 years old) patients with confirmed diagnosis of CD, who commenced therapy with UST as 1^st, 2^nd, or 3rd line biologic treatment, according to physician’s decision, local standards of clinical practice and as per label indication. Data were collected by routine assessments, including Harvey-Bradshaw Index (HBI), and PROs at baseline (start of UST) and follow-up visits every 6-months. Last visit was done at month 24 (±2 months) or at treatment discontinuation (whichever occurred first). Drug persistence, disease activity and safety outcomes over the 24-month observation period are presented herein.

Results

A total of 169 eligible patients were enrolled in 19 Gastroenterology Clinics in Greece between April 2019 and February 2021. At baseline, median age was 45.0 years, 50.9% (86/169) of patients were females, 43.4% (72/166) were employed, and 68.5% (113/165) were former or current smokers. UST was the 1st, 2^nd, and 3rd biologic treatment in 35.5% (60/169), 35.5% (60/169), and 29.0% (49/169) of patients, respectively. The median duration of study participation was 23.9 months (median number of injections received: 13.0). At 24 months, 21.9% (37/169) of patients had discontinued UST after a mean of 10.2 months due to lack/loss of response (15/37), safety issues (10/37), lost at follow-up (6/37), patient’s wish (2/37), death (2/37; both unrelated to UST), pregnancy (1/37) and patient issues (1/37). The Kaplan-Meier (KM)-estimated median drug survival (i.e., time to treatment discontinuation) was not reached in the overall population or subgroups by treatment line, with no statistically significant differences in the risk of UST discontinuation between subgroups of interest [2L vs 1L: hazard ratio (HR)=1.07, 95% confidence interval (CI)=0.48-2.39; 3L vs 1L: HR=1.54, 95% CI=0.70-3.40; 3L vs 2L: HR=1.42, 95% CI=0.65-3.11). The KM-estimated UST treatment-persistence rates for the overall population s were 86.7%, 80.5%, and 78.0%, at 12-, 18-, and 24-months, respectively. The baseline median total ΗΒΙ (8.0) significantly improved (P<0.001) at 12, 18, and 24 months, with a median 4-point reduction at each timepoint, among paired observations. Significant improvements were also noted based on imputed data and in the subgroups per treatment line. The adverse event (AE), serious AE, and UST-related AE rates were 63.9% (108/169), 18.9% (32/169), and 19.5% (33/169), respectively. Each UST-related AE was reported in <4.0% of the patients. Further details on baseline characteristics, 12/18/24-month outcomes, and UST-related AEs are presented in Table 1.

Conclusion

Our data provide RWE for high persistence rate of treatment with UST in our series with Greek patients with CD. Treatment with UST demonstrated a highly favorable effect on disease activity, in combination with a predictable safety profile.

Disclosure

Disclosure: This study was sponsored by Janssen - Cilag, Greece.

Giorgos Bamias Advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma, Adacyte Therapeutics, Amgen, Ferring, Cooper, BMS; Funding (Grants/Honoraria): Pfizer, Takeda, Abbvie, Aenorasis; Research/Clinical Trials: Abbvie, Takeda, Janssen.
Gerassimos J. Mantzaris has received consultant and/or speaker fees from AbbVie, MSD, Celtrion,Ferring, Aenorasis, Janssen, Pfizer, Takeda, Falk Pharma, and Vianex and research support from AbbVie, Ferring, MSD, and Vianex
Maria Tzouvala has received clinical research funding from Janssen-Cilag Pharmaceuticals SACI, Takeda HELLAS SA, AbbVie Pharmaceuticals S.A. Consulting and/or speaking fees MSD Sharp& Dohme, Janssen-Cilag Pharmaceuticals SACI, Takeda, AbbVie Pharmaceuticals S.A, Pfizer, Amgen. Advisory boards: Janssen-Cilag Pharmaceuticals SACI, Takeda, AbbVie Pharmaceuticals S.A, Pfizer, Amgen
Dimitrios Christodoulou has received consulting and speaking fees for Janssen, MSD, Galenica. Advisory Board for Galenica
Ioannis Koutroubakis has received clinical research funding: Abbvie, Faran, Ferring, Pfizer, Viatris, Vianex, Vifor, Unipharma. Consulting and/or speaking fees Abbvie, Genesis, Janssen, MSD, Takeda, Vianex. Advisory boards: Abbvie, Janssen, MSD, Pfizer, Takeda, Vianex
Christos Liatsos has received clinical research funding from: Janssen, and consulting and/or speaking fees from: MSD, Pfizer, Boston SCI, Amgen, Galenica.
Georgios Papatheodoridis Clinical research funding: Abbvie, Gilead, Takeda, Vianex. Consulting and/or speaking fees: Abbvie, Astra-Zeneca, BioARS Therapeutics, Elpen, Genesis, Gilead, GlaxoSmithKline, Ipsen, Novo Nordisk, Roche, Sobi. Advisory boards: Abbvie, Astra-Zeneca, Albireo, Amgen, Galenica, Genesis, Gilead, GlaxoSmithKline, Ipsen, Janssen, Novo Nordisk, Roche, Takeda
Dr Katsanos Konstantinos received honoraria for consulting services (educational services, scientific articles, participation in Advisory Boards, clinical trials, lecture fees, other) from the companies as follows:AbbVie, AMGEN, ENORASIS, Epsilon Health, Ferring, Genesis, Grifols S.A., JANSSEN, MSD, Mylan, Shire and Takeda.
Evanthia Zampeli has received clinical research funding: Janssen, TAKEDA, ABBVIE. Consulting and/or speaking fees: Janssen, TAKEDA, BMS, AMGEN, MYLAN. Advisory boards: BMS, GALENICA
Georgios Germanidis has received clinical research funding from Janssen.
Konstantinos Soufleris Consulting and/or speaking fees: AbbVie, Janssen, MSD, Pfizer, Takeda. Clinical research funding:Pfizer. Advisory board: BMS, Galenica.
Matina-Lydia Chatzinikolaou has received consulting fees from Abbvie, Takeda, Amgen, Ferring, Janssen
George Kokkonis has received clinical Research funding from Janssen and speaking fees from Janssen and Amgen
Alexandros Boubonaris has served as advisory board member for Amgen, Takeda
Marios Giakoumis has received clinical research funding from Janssen
Artemis Trikola has received clinical research funding from Janssen
George Michalopoulos has received speaker fees : Takeda, MSD, , Abbvie, Jannsen, Pfizer, Amgen
Vasileios Delis, Konstantina Paraskeva, Theodosios Sdonas, Athanasia Tasovasili, Evgenia Papathanasiou, Maria Palatianou, Andreaddds Nakos, Nikoletta Mathou, George Kalopitas, Panagiotis Giannelis, Kalliopi Foteinogiannopoulou, Konstantina Chalakatevaki, Eleni Beka, Chara Lamouri, Eleftheria Giannakoulopoulou have no conflicts to disclose.
Konstantinos Thomopoulos, Stergios Vradelis, Andreas Protopapas, Ioannis Pachiadakis, Ioannis Goulis, Pantelis Karatzas, George Theocharis, George Tribonias, Angeliki Machaira, Nikolaos Kyriakos, Adonis Protopapas, Konstantinos Fasoulas, Eleni Orfanoudaki and Charilaos Taloumtzis have not disclosed any conflicts.
Spyridon Michopoulos has received clinical research funding from Janssen, Takeda, BMS, consulting and/or speaking fees from Takeda, and has served as advisory board member for Takeda.
Christos Gkamaloutsos, Ioannis Kanistras and Aikaterini Mpartsea are employees of Janssen - Cilag, Greece.