Introduction

Early-stage colorectal cancer (T1CRC) patients are confronted with complex medical information and considerations throughout the course of their treatment. This study explored patients’ perspective on information provision and therapeutic decision-making.

Aims & Methods

Patients who underwent endoscopic or local surgical resection for T1CRC were eligible for participation in this cross-sectional multicenter study. Information provision was evaluated using the EORTC QLQ-INFO25 questionnaire (INFO25)(1). In patients with a high-risk T1CRC we additionally evaluated patients’ perception of involvement in decision-making regarding the choice to opt for or refrain from additional treatment after local resection, and the degree of decisional conflict using the decision conflict scale (DCS)(2).

Results

In the 98 responders (response rate: 71.5%), patients with high-risk T1CRC (n=45) reported to have received more information on multiple disease aspects compared to patients with low-risk T1CRC (n=53). However, the need for more information was not significantly different between both groups (p=0.31). Overall, 29 patients expressed a need for more information, with ‘prevention’ and ‘post-treatment care’ reported as the most common areas with unmet information needs. Of the 45 patients with high-risk T1CRC, 24 (53.3%) underwent additional treatment, whereas 21 (46.7%) opted for close monitoring. Twenty-seven patients (60%) reported that they were actively involved in this decision (i.e. ‘I made the decision myself’), while 18 patients (40%) reported to be passively involved (i.e. ‘I let my physician make the decision’ or ‘I didn't feel like there was a choice’). Satisfaction scores regarding information provision were similar between patients that underwent additional treatment or opted for close monitoring (range 0-100, 70.8 vs. 73.0, p=0.77). Higher educated patients were more likely to report active involvement in therapeutic decision-making compared to lower educated patients (92.9% vs. 43.3%, p=0.002) and to eventually undergo additional treatment (78.6% vs. 40%, p=0.02). The satisfaction scores regarding how the treatment decision was made did not differ significantly between patients with higher and lower levels of education (range 0-100, 83 vs. 85.1, p=0.78).

Conclusion

From the T1CRC patient’s perspective, this study found that higher educated patients were more likely to be actively involved in therapeutic decision-making than lower educated patients, although decisional satisfaction was irrespective of educational level. With respect to information needs, patients expressed a desire for more information on disease prevention and post-treatment care.

References

1. Arraras JI, Greimel E, Sezer O, Chie W-C, Bergenmar M, Costantini A, et al. An international validation study of the EORTC QLQ-INFO25 questionnaire: An instrument to assess the information given to cancer patients. European Journal of Cancer. 2010;46(15):2726-38.
2. O'Connor AM. Validation of a decisional conflict scale. Med Decis Making. 1995;15(1):25-30.

Introduction

In the southwest Netherlands, hospitals collaborate to provide high quality, uniform care for inflammatory bowel disease (IBD). To achieve this, a care pathway (CP) was implemented for treating IBD with biologics and small molecules (1). The CP consists of protocols addressing different stages in IBD treatment, such as initiation and switching of therapy, frequency and type of follow-up. This study assessed the adherence to the CP and identified barriers and facilitators to its implementation.

Aims & Methods

A mixed-methods study was conducted. Quantitative data was used to evaluate the adherence to different protocols of the CP and was collected retrospectively from electronic health records (EHRs) from December 2020 until March 2023. Surveys and semi-structured interviews were used to identify barriers and facilitators, using the Extended Normalisation Theory. Surveys were sent to all healthcare providers and interviews were conducted with gastroenterologists, IBD-nurses, healthcare assistants, and IT-personnel.

Results

A total of 299 patients were included. Adherence to the CP regarding the documentation of travel plans and vaccination status improved after implementing the CP (15% pre-implementation vs. 33% post-implementation), as well as written communication with general practitioners (31% vs. 83%) and body weight registration (12% vs. 50%). Among patients switching medication, 25% had a repeated screening for HIV, tuberculosis, and hepatitis B and C documented if prior tests were over a year old. Post-implementation, scheduling outpatient visits were more closely aligned with CP recommendations across CP protocols (57% vs. 100%), as did blood test ordering (10% vs. 44%). Disease activity scoring with validated questionnaires remained low (7% vs. 21%).  Adherence to registering medication adherence, current smoking status, and side effects during annual outpatient visits remained low (18% vs. 40%).
Of 85 surveys, 42 were completed, and 11 interviews were conducted. Facilitators were improving collaboration between healthcare providers and the potential to standardise care. Barriers included the complexity of the use in EHRs, difficulty for healthcare providers to change their current routine, and the heterogeneity of IBD.

Conclusion

A CP for the treatment of IBD with biologics and small molecules has been implemented to improve IBD care, however, adherence appears to be challenging, partially contributed to the difficulty healthcare providers experience in changing their behaviour. The gradual improvement indicates that increased familiarity with the CP may enhance adoption. Discrepancies between performed and documented tasks in EHRs may also contribute to lower adherence rates, which could be improved by audit and feedback sessions.

References

1. van Linschoten R, van Leeuwen N, Nieboer D, Birnie E, Scherpenzeel M, Verweij KE, et al. Value-based care pathway for inflammatory bowel disease: a protocol for the multicentre longitudinal non-randomised parallel cluster IBD Value study with baseline period. (2044-6055 (Electronic))

Disclosure

Drs. Visser received speaker fees from Lilly outside the submitted work. Prof. Dr. van der Woude reports grants from Pfizer and Janssen and personal fees from AbbVie and Celltrion outside the submitted work. Dr. van Noord reports personal fees from Janssen, Takeda, and Falk outside the submitted work. Dr. West reports personal fees from AbbVie, Janssen, and Pfizer outside the submitted work.

Introduction

Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn’s disease (CD). Both diseases are different but show an uncontrolled intestinal immune response that generates tissue inflammation. Dendritic cells (DC) are phagocytic professional antigen presenting cells that link the innate and adaptive immune systems. Indeed, they are the only cell type able to stimulate naïve T cells generating an antigen-specific immune response. In humans, DC can be divided into plasmacytoid (pDC) and c conventional type 1 and 2 (cDC1, cDC2). Although cDC migration towards the GI mucosa is enhanced in IBD, the mechanisms underlying these migrations and whether biological drugs can modulate them are currently unknown.

Aims & Methods

This study aimed to analyze DC migratory capacity towards the GI mucosa, and whether biological drugs with different mechanisms of action can modulate this process in health and IBD.This is a cross-sectional observational postmarketing study where the modulatory effect of different biological treatments on samples from patients with an endoscopic diagnosis of IBD and healthy controls was studied ex vivo. Peripheral blood mononuclear cells (PBMC) were obtained from 15 patients per group and were cultured in presence of golimumab or ustekinumab. Following culture, surface markers expression was determined, assessing the differential effect of biological drugs (if any) over the DC subsets in the different groups. After that, the migratory capacity of circulating DC towards CCL2, CCL25, and MadCam1 from the different study groups was determined. Finally, we evaluated the DC migratory capacities in presence of biological drugs or with culture media alone.

Results

The cDC2 subset showed higher expression levels of β7 and CCR5 compared to cDC1. Golimumab and ustekinumab did not modify the expression of the homing markers in any studied subset in pDC and cDC2.On the contrary, in cDC1 both golimumab and ustekinumab increased CCR6 expression in qCD patients and CCR9 in aUC patients. Regarding to the migratory capacities of the different DC subsets toward intestinal chemoattractants ustekinumab decreased the migratory capacity of cDC2 from CD patients towards a medium supplemented with MadCam1 and increases toward CCL2 in case of cDC1 from CU. In the case of migratory capacities of cDC2 from HC were increased by ustekinumab and golimumab toward CCL2 and CCL25 just in case of golimumab.

Conclusion

cDC2 showed more migratory profile markers than other DC populations. Golimumab and ustekinumab modify the expression of the homing markers just in cDC1 subset. Nevertheless, ustekinumab and golimumab modify the migratory capacities of cDC in IBD patients and HC, but do not exert any effect on pDC. These effects occur in a different manner in CD and UC indicates that the behavior of cDC is different in CD and UC, and that the migration capacity of this subset is not dependent exclusively on homing markers.

Introduction

To examine the evolution of the ulcerative colitis (UC) treatment pathway in advanced therapy (AT) naïve and later line EU4+UK patients over time, as well as identifying how treatment goals may have changed.

Aims & Methods

A multi-centre online medical chart review study of patients with UC was conducted between Jan – Mar 2018, Jul – Sep 2020 and Jan – Mar 2023, among EU4+UK (UK, FR, DE, IT & ES) gastroenterologists practicing across hospital and private practices. Recruited physicians were screened for duration of practice in their specialty and caseload. Respondents completed patient record forms of their next 4 UC patients seen following receipt of the survey.

Results

The total number of sampled gastroenterologists recruited in this survey and reported UC patients are in Table 1.

Table 1: Sampled physician and reported patient sample size

Timepoint	Q1 2018	Q3 2020	Q1 2023
Surveyed gastroenterologists	207	211	220
Reported UC patients	816	844	880

Between Q1’18 – Q3’20 - Q1’23 the percentage usage of total adalimumab volume in reported UC patients dropped (30% vs 15% vs 13%, respectively), as well as the proportion of these patients reported as first line adalimumab patients (90% vs 88% vs 87%, respectively). In addition, the proportion of reported patients who experienced a switch from one TNF to another also drops between Q1’18 – Q3’20 (14% vs 10%, respectively). Conversely, the proportion of reported UC patients receiving a non-TNF therapy increases over time (12% vs 29% vs 43%, respectively); specifically, the proportion of reported non-TNF first line patients increased (5% vs 12% vs 25%, respectively). Switches from non-TNFs to TNFs increased between Q1’18 – Q3’20 (8% vs 11%, respectively). The proportion of the overall sample occupied by first line patients decreased between Q1’18 – Q3’20 (84% vs 77%, respectively).

Conclusion

In this study cohort, use of adalimumab molecule decreases over time, seemingly in favour of non-TNF therapies, as more products become available in the gastroenterology landscape. This trend is seen across both the overall market and at first line of therapy, suggesting a move away from use of the more ‘traditional’ therapies in general, as well as more frequently choosing a non-TNF as a first line option. The increasing proportion of non-TNF 1st line patients, as well as the increasing proportion of those switching from non-TNFs to TNFs, suggests an increasing proclivity to use non-TNF products earlier in the treatment algorithm. TNF cycling also decreases, suggesting an increased tendency to use non-TNF products. This, along with the decreasing proportion of the sample occupied by first line patients, could indicate an increased propensity by gastroenterologists to switch patients between therapies sooner. Further investigation using comparator cohort is warranted to further investigate impact of increasing numbers of approved UC treatment options.

Introduction

Cobitolimod (MW 5925.18 Da) is a DNA-based oligonucleotide functioning as an immunomodulatory Toll-like receptor 9 agonist. Cobitolimod is in phase III clinical development as a new therapy for moderate to severe left-sided ulcerative colitis (UC). This phase Ib study aimed to evaluate the pharmacokinetics (PK), safety and tolerability of rectally administered cobitolimod in patients with moderate to severe UC.

Aims & Methods

The phase Ib open-label study was conducted at a single center in Sweden (NCT05404074). The patients had moderate to severe UC defined by a 3-component Mayo score of 5 to 9, with an Investigator read endoscopic subscore ≥2, and with stool frequency and rectal bleeding subscores each ≥1. Patients received one cobitolimod enema (500 mg/50 ml) at week 0, and blood samples for PK analysis were collected pre-dose, 15 min, 30 min, 1h, 2h, 4h, 8h, 12h and 24h after dosing. Patients received a second cobitolimod enema (500 mg/50 ml) at week 3, and at week 6 the degree of clinical remission was evaluated. Clinical remission was defined by the 3-component Mayo score with a rectal bleeding subscore = 0, a stool frequency subscore ≤1 (≥1 point decrease from baseline), and an Investigator read endoscopic subscore ≤1. Patients in clinical remission at week 6 received a third cobitolimod enema (500 mg/50 ml), and blood samples were collected for a second PK analysis as described above. The primary endpoint was PK parameters: maximum plasma concentration (C_max), time to C_max (T_max), area under the curve from 0 to timepoint t (AUC_t) and half-life (T_1/2). Secondary endpoints included safety and tolerability.

Results

Eight patients with active disease were enrolled in the study and included in the safety analysis set. One patient was excluded from the pharmacokinetic analysis set (PKAS) due to an immediate bowel movement following administration. Of the 7 patients included in the PKAS, 4 patients achieved clinical remission at week 6. Rectal administration of 500 mg cobitolimod at week 0 resulted in median C_max of 21.7 ng/ml, median T_max of 1h, median T_last of 4h, and median AUC_0-last of 71.7 h*ng/ml (n=7). For the 4 patients in remission at week 6, corresponding numbers were: median C_max of 15.5 ng/ml, median T_max of 0.5h, median T_last of 4h and median AUC_0-last of 27.6 h*ng/ml. T_1/2 was <2.5h both at week 0 and week 6.
In total, 24 adverse events occurred in the study, out of which the majority was mild and judged as unlikely related to study drug. No serious adverse events were reported.

Table 1. PK parameters per patient

Patient No	Tmax (h)		Cmax (ng/mL)		AUClast (h*ng/mL)		Tlast (h)
	Week 0	Week 6	Week 0	Week 6	Week 0	Week 6	Week 0	Week 6
101*	1	0.5	165.0	6.4	371.6	11.7	4	4
102	1	-	17.0	-	28.1	-	4	-
103*	2	0.5	19.9	24.5	71.7	36.4	8	4
105*	2	1	51.9	9.4	192.5	18.9	8	4
106	2	-	43.8	-	149.7	-	8	-
107*	1	0.5	20.0	21.6	29.2	66.7	4	4
108	0.5	-	21.7	-	25.6	-	4	-

*Patients in clinical remission at week 6 received a 3^rd dose of cobitolimod for a 2^nd PK analysis.

Conclusion

The study demonstrates that rectally administered cobitolimod results in a low systemic exposure of short duration both in patients with active disease and in clinical remission. Cobitolimod was safe and well tolerated at a dose of 500 mg.

Disclosure

Thomas Knittel is a consultant for and a shareholder in InDex Pharmaceuticals, Sweden. Pernilla Sandwall is a former employee and a shareholder in InDex Pharmaceuticals, Sweden. Christine Dieterich Johansson is employed by InDex Pharmaceuticals, Sweden. Arezou Zargari is employed by and a shareholder in InDex Pharmaceuticals, Sweden. Johan Bring is a consultant for InDex Pharmaceuticals, Sweden. Per Hellström receives consultancy fees from: Clinical trial consultants, Sweden; ROSE pharma, USA; Pharmanovia, Denmark; Swedish Agricultural University, Uppsala; Pharmacosmos, Denmark; Stockholm Diabetes Association, Sweden; Celltrion, Finland; Mag-tarmförbundet, Sweden; Karolinska Institutet, Sweden; Bristol-Myers Squibb, Sweden; ClinSmart, Sweden; InDex Pharmaceuticals, Sweden; Takeda pharmaceutical company; Mediahuset, Sweden; Bonnier Healthcare Sweden; Folkuniversitetet, Stockholm, Sweden; Biogaia, Stockholm, Sweden; Norgine, Denmark; Nanologica AB, Södertälje, Sweden.

Introduction

Not all patients with ulcerative colitis (UC) respond initially to treatment with biologic agents, and predicting their efficacy prior to treatment is difficult. Vedolizumab, a humanized monoclonal antibody against alpha 4 beta 7 (α4β7) integrin, suppresses immune cell migration by blocking the interaction between α4β7 integrin and mucosal addressin cell adhesion molecule 1, and is used to treat patients with UC with moderate-to-severe activity. Reports about histological features that predict vedolizumab efficacy are scarce.

Aims & Methods

We evaluated the infiltration of inflammatory cells in the colonic mucosa prior to the induction of vedolizumab and examined the association between histological features and vedolizumab efficacy.
This was a multicenter, retrospective study. Patients with UC who were treated with vedolizumab between November 2018 and April 2021 were enrolled in this study. All eligible patients had moderate-to-severe disease activity at the time of the initial treatment with vedolizumab. Biopsy specimens taken from the colonic mucosa prior to vedolizumab induction were used, and the areas positively stained for CD4, CD68, and CD45 per unit area of the lamina propria were calculated. Clinical and histological features were compared between those with and without remission at week 22, and the factors associated with clinical outcomes were identified.

Results

A total of 42 patients were included in this study. 17 (40.5%) patients achieved clinical remission at week 22. Significantly more CD4+ cells were found in the colonic mucosal tissues of patients with remission than in those without remission (odds ratio [OR]=1.44, P=0.014). In contrast, the CD68-positive area and the CD45-positive were not significantly different between the two groups. The concomitant use of corticosteroids and high Mayo scores had a negative association with the vedolizumab response (OR=0.11, P=0.008 and OR=0.50, P=0.009, respectively).

Conclusion

A high CD4+ infiltration in the colonic mucosa was associated with remission after vedolizumab treatment. Histological evaluation for CD4+ cell infiltration may be helpful in selecting patients who can benefit from vedolizumab.

Introduction

In contrast to ulcerative colitis (UC), the impact of bowel urgency (BU) in patients with moderate-to-severe Crohn’s disease (CD) is unclear. The Communicating Needs and Features of IBD Experiences (CONFIDE) survey aims to understand the experience and impact of symptoms on lives of patients with UC or CD worldwide (United States [US], Europe [EU], and Japan). This survey also explores the communication gaps between healthcare professionals (HCPs) and patients. Previously reported CONFIDE data suggested that BU was the second most reported symptom among US and EU5 (France, Germany, Italy, Spain, and UK) patients with moderate-to-severe UC.¹ Persistent BU was reported in 46% US and 28% EU5 patients receiving advanced therapies for UC and 45% US and 37% EU5 patients reported wearing diapers/pads/protection at least once every week.¹ Here, we present patient and HCP perspectives on the experiences and impact of CD-related symptoms.

Aims & Methods

Online, quantitative, cross-sectional surveys were conducted separately among HCPs and patients with CD from US and EU5 between May and October 2021. Moderate-to-severe CD was defined using criteria based on previous treatment, steroid use, and/or hospitalization. Data are presented as descriptive statistics.

Results

Surveys were completed by 215 US (male [M]=55%, mean age 41 years) and 547 EU5 (M=55%, mean age 38 years) patients. Of these, 58% US and 63% EU5 patients were receiving advanced therapies (biologic/novel oral) and 66% and 63% were receiving steroids at the time of survey completion, respectively. Most patients in the US (61%) and EU5 (62%) reported moderate CD, followed by severe (25% and 10%), and mild CD (14% and 28%).
In both US and EU5 populations, top three symptoms currently (past month) experienced by patients were diarrhoea (US: 55%, EU5: 55%), BU (US: 42%, EU5: 38%), and increased stool frequency (US: 40%, EU5: 37%). Among the patients receiving advanced therapies (US: 58%, EU5: 63%), 46% US and 39% EU5 patients experienced BU and 27% US and 19% EU5 patients reported fistula-related symptoms around the anus/rectum. Of the patients who had experienced BU, only 40% US and 27% EU5 patients were completely comfortable discussing BU with their HCPs and only 27% US and 23% EU5 patients felt comfortable discussing BU-related accidents. Embarrassment was the most common reason for discomfort associated with discussing BU (US: 73%, EU5: 64%) and BU-related accidents (US: 72%, EU5: 66%) with HCPs.
A total of 200 US (M=78%) and 503 EU5 (M=71%) HCPs completed the surveys, of which 92% were gastroenterologists or specialists in internal medicine and 7% were non-physicians. According to HCPs, the top three patient-reported symptoms were diarrhoea (US: 67%, EU5: 66%), blood in stool (US: 44%, EU5: 24%), and increased stool frequency (US: 32%, EU5: 28%). BU was reported among the top three symptoms only by 19% US and 16% EU5 HCPs. Many HCPs (US: 34%, EU5: 40%) reported not proactively discussing BU, with the most common reason being that they “expect the patient to bring this up if this is an issue” (US: 34%, EU5: 42.0%).

Conclusion

Similar to the findings in UC patients¹, bowel urgency was the second most reported symptom among patients with CD, but not among the HCP-perceived top three symptoms. A large proportion of patients with moderate-to-severe CD receiving advanced therapies continued to experience bowel urgency. These results indicate a communication gap between HCPs and patients with CD, highlighting the underappreciation of the impacts of bowel urgency on patients’ daily lives.

References

1. Rubin, D. T. et al. (2021) P028 Communicating Needs and Features of IBD Experiences (CONFIDE) Survey: Patient and Healthcare Professional Perspectives on Experience of Ulcerative Colitis Symptoms. The American Journal of Gastroenterology, 116:p S7. https://doi.org/10.14309/01.ajg.0000798712.28363.8b

Disclosure

• Simon Travis, Grants: AbbVie, ECCO, Eli Lilly and Company, Helmsley Trust International, Organization for the Study of Inflammatory Bowel Disease, Norman Collision Foundation, Pfizer, Takeda, UCB Pharma, UKIERI, Vifor Pharma; Consultancy fees: AbbVie, Allergan, Amgen, Apexian, Asahi Kasei Pharma, Bioclinica, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, ChemoCentryx, Cosmo Pharmaceuticals, Eli Lilly and Company, Enterome, Equillium, Ferring Pharmaceuticals, Genentech/Roche, GlaxoSmithKline, Giuliani SpA, Immunocore, Immunometabolism, Janssen, Merck, Merck Sharp & Dohme, Mestag Therapeutics, Neovacs, Novartis, Novo Nordisk, NPS Pharmaceuticals/Nycomed, Pfizer, Protagonist Therapeutics, Proximagen, Receptos, Roche, Satisfai Health, Sensyne Health, Shire, Sigmoid Pharma, Sorriso Pharmaceuticals, Takeda, UCB Pharma, VHsquared, Vifor Pharma, and Zeria Pharmaceutical.
• Marla C. Dubinsky, Consultancy fees: AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Celgene Corporation, Eli Lilly and Company, F. Hoffman-La Roche Ltd, Genentech Inc., Gilead Sciences, Janssen, LLC, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals USA, Inc., and UCB; Stockholder: Trellus Health Inc.; Research support: AbbVie, Janssen, LLC, Pfizer, and Prometheus Biosciences; Licensing fees: Takeda.
• Toshifumi Hibi, Consultancy fees/grant/research support/speaker: AbbVie GK and Mitsubishi-Tanabe Pharma; Grant/Lecture/speaker fees: JIMRO, Mochida Pharmaceutical, Takeda Pharmaceutical, and Zeria Pharmaceutical; Consultancy/ Lecture/speaker fees: Pfizer, EA Pharma; Grants: Kyorin, Otuska Holdings; Consultancy fees: Bristol-Myers Squibb, Eli Lilly and company, Gilead Sciences, Janssen, Nichi-Iko Pharmaceutical; Lecture/speaker fees: Sondoz K.K.
• David T. Rubin, Consultancy fees: Abbvie, Alimentiv Inc., Altrubio, Arena Pharmaceuticals, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim Ltd., Bristol-Myers Squibb, Celgene Corp/Syneos, ClostraBio, Connect BioPharma, EcoR1, Genentech/Roche, Gilead Sciences, Ironwood Pharmaceuticals, Iterative Scopes, Janssen Pharmaceuticals, Kaleido Biosciences, Eli Lilly and company, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Seres Therapeutics, Takeda, Target RWE, Techlab Inc., and Trellus Health; Stockholder: Altrubio, Alike, and Iterative Scopes.
• Remo Panaccione, Consultancy/speaker fees and/or advisory board member: AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda; Consultancy fees and/or advisory board member: Alimentiv, AstraZeneca, Biogen, Boehringer Ingelheim, Genentech, Glaxo-Smith Kline, JAMP Bio, Mylan, Novartis, Oppilan Pharma, Pandion Pharma, Progenity, Protagonist Therapeutics, Sublimity Therapeutics, Ventyx; Consultancy fees: Abbivax, Abbott, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Galapagos, JAMP Bio, Pendopharm, Satisfai Health, Theravance Biopharma, Trellus, Viatris, and UCB.
• Stefan Schreiber, Consultancy fees: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Falk, Fresenius, Gilead Sciences, IMAB, Janssen, Eli Lilly and Company, MSD, Mylan, Pfizer Inc, Protagonist, Provention Bio, Takeda, and Theravance
• Christian Atkinson, Employee: Adelphi Real World
• Theresa H. Gibble, Cem Kayhan, Alison P. Bleakman, Tommaso Panni, and Angelo Favia are employees and stockholders of Eli Lilly and Company.