Introduction

Delayed bleeding is a frequently observed complication after endoscopic mucosal resection of large adenomas of colorectum and duodenum. Even though the associated mortality is low, delayed bleeding causes significant morbidity and use of health care resources. Clip closure of the resection field reduces delayed bleeding, but it is time consuming and often complete closure is not achieved. Hemostatic gels and powders can be applied quickly and easily. These agents are in use for the treatment of active bleeding, but it is unknown, whether they will also prevent delayed bleeding when applied to the resection field prophylactically.

Aims & Methods

We conducted a randomized controlled trial of patients undergoing hot-snare endoscopic mucosal resection of flat lesion in the duodenum and colorectum at 15 centers in Germany. Lesions had to be non-pedunculated and measure at least 10 mm in the duodenum and 20 mm in the colorectum. Immediately after resection was completed patients were randomized to hemostatic gel application (intervention group) or no prophylaxis (control group). The primary endpoint was clinically significant delayed bleeding rate (CSDB) within 30 days after resection. Secondary endpoints included transfusion requirements, other complications, wound healing and lesion recurrence.

Results

A total of 233 patients were included in the trial. We performed a planned interim analysis when 200 patients were available for evaluation of the primary end point; at this point we stopped enrollment in the trial due to futility. Of the 200 patients included in the interim analysis, 100 (88 colorectal, 12 duodenal) were included in the intervention group and 100 (88 colorectal, 12 duodenal) in the control group. Groups were comparable in terms of patient age, sex, comorbidities, and lesion localization. CSDB occurred in 13 cases (13%) in the intervention group and in 6 cases (6%) in the control group. This difference was not statistically significant (p=0.146 Fisher’s Exact Test). CSDB rates for colorectal lesions were 10% vs. 4.5% (intervention vs. control group) and for duodenal lesions 33% vs. 17%. Follow-up for patients already enrolled is continuing and data lock for the full study cohort is expected in May 2024. The full data set will be presented at UEG Week.

Conclusion

The application of a hemostatic gel following endoscopic mucosal resection of large non-pedunculated lesions in the duodenum and colorectum does not reduce the rate of CSDB.

Disclosure

OM and TVH have received lecture fees from Puramatrix (the company producing Purastat gel). TW has received lecture fees from Fuji (the company marketing Purastat in Germany).

Introduction

Risankizumab is a selective IL23 inhibitor that was approved by the FDA for the treatment of moderately to severely active Crohn’s disease (CD) in June 2022. The effectiveness of risankizumab in ustekinumab-experienced patients is of particular interest due to a similar mechanism of action. Here, we present our one-year experience of risankizumab treatment in CD patients, with a focus on the comparison between ustekinumab-naïve and ustekinumab-experienced patients.

Aims & Methods

We prospectively followed patients with CD treated with risankizumab in our center and documented their clinical disease activity using Harvey-Bradshaw Index (HBI) score at baseline and at weeks 12, 26, and 52 after treatment initiation. We included patients who were treated for active luminal disease, defined as HBI≥5, fecal calprotectin (FCP) ≥250, steroid dependance or who had evidence of active disease per ileocolonoscopy or imaging in the effectiveness analysis. We excluded from the effectiveness cohort patients with ileostomy, J-pouch or surgery within the 6 months prior to risankizumab commencement. We recorded adverse events in all patients. Patients who stopped treatment due to ineffectiveness or intolerance were counted as non-responders for the purpose of remission-rate calculations at each time point.

Results

253 patients were treated with risankizumab and had at least 12 weeks of follow up. 153 patients were included in the effectiveness cohort. Demographics and patient characteristics are detailed in Table 1. At week 12, 71.3% (92/129) achieved clinical remission (CR), and 63.6% (82/129) achieved steroid-free clinical remission (SFCR). At week 26, 64.5% (60/93) and 62.4% (58/93) achieved CR and SFCR respectively. At 1 year, CR rate was 53.3% (40/75), and SFCR rate was 48% (36/75). Median FCP was 385.5µg/g (IQR 168.25-905, n=33) at baseline, 102.5µg/g (IQR 39-354, n=20) at week 12, 118µg/g (IQR 40-183, n=24) at week 26, and 63µg/g (IQR 19-122, n=16) at 1 year. 79.6% (74/93) remained on risankizumab 6 months after treatment initiation, and 64.3% (52/75) of patients remained on treatment at one year. In the effectiveness cohort, 47.7% (73/153) of patients were ustekinumab-naïve, and 53.3% (80/153) were ustekinumab-experienced. SFCR rates in ustekinumab-naïve and ustekinumab-experienced patients were 73.8% (45/61) vs. 54.4% (37/68) at week 12 (p=0.0282), 67.4% (31/46) vs. 57.4% (27/47) at week 26 (p=0.3936), and 54.1 (20/37) vs. 42.1% (16/38) at one year (p=0.3588), respectively.
Minor adverse events were documented in 12.6% (32/253) of patients, including fatigue, pruritus, nausea, joint pain, and upper-respiratory tract infection. One patient had a suspected allergic reaction to the first infusion and treatment was not continued. In 1.9% (5/253) of patients, treatment was discontinued d/t adverse events. No serious adverse events were observed.

Characteristic	All patients (n=253)	Patients in the effectiveness cohort (n=153)
Age, y, median (IQR)	42 (30-54)	41.5 (30.25-54)
Disease duration y, median (IQR)	14 (9-22)	12 (8-22.75)
Female sex, n (%)	151 (60.9)	89 (58.2)
White race	198 (80.2)	116 (75.8)
Smoking history, n (%) current former	13 (5.3) 56 (23)	10 (6,6) 38 (25)
Baseline HBI, median (IQR)	5 (2-8)	5.5 (3-9)
Advanced therapy naïve n (%)	28 (11)	14 (9.1)
History of bowel resection, n (%)	158 (65)	89 (59.3)
Steroid treatment at baseline, n (%)	61 (29)	48 (33.6)

Conclusion

In this large real-world experience in patients with CD, we found that risankizumab has excellent efficacy and safety, with notable effectiveness in ustekinumab-experienced patients.

Introduction

The BELCOMID study recruited immune mediated inflammatory disease (IMID) patients during the COVID19 pandemic. Patients were evaluated before vaccination, after onset of the vaccination campaign and after onset of booster vaccinations. Clinical data, Nucleocapsid(N-)antibodies and Spike(S-)antibodies were assessed.

Aims & Methods

Current subgroup analysis aimed to firstly, explore factors associated with N-/S-antibody response in IMID patients with different COVID19 vaccination status. Five patient groups were identified. G1: no vaccination before the vaccination campaign, G2: complete baseline vaccination, G3: 1 booster, G4: 2 boosters, G5: patients refusing every vaccine even after the booster campaign. We report on influence of IMID treatment and smoking status.
Secondly, we explored influence of SARS-CoV2 infection and vaccination on IMID flare-up.

Results

Demographics of 2165 recruited IMID patients are shown in Table.
After baseline vaccination (G2) odds of N-seroconversion were higher in patients treated with combined IMM/TIMT (OR2.52, p=0.023). No other association with N-seroconversion was found.
Mean S-antibody titre increased progressively from G2 to G4. After completed baseline vaccination (G2), odds of S-antibody seroconversion were lower in those treated with TIMT (OR0.28, p=0.0079) particularly rituximab (OR0.0354, p<0.001), IMM (OR0.276, p<0.001), combined IMM/TIMT (OR0.156, p<0.001) and systemic steroids (OR0.183, p<0.001). IMID flare prior to vaccination was associated with lower risk of S-seroconversion (RR0.94, p<0.001). By contrast, mean S-titre was higher for those treated with antiIL23 (mean ratio 2.17, p=0.011) and vedolizumab (mean ratio 1.84, p<0.001) in G2.
After 1 booster (G3), lower odds of S-seroconversion remained with rituximab (OR0.0368, p<0.001), IMM (OR0.222, p=0.0014), combined IMM/TIMT (OR0.15, p<0.001) or systemic steroids (OR0.0637, p<0.001). Vedolizumab was associated with lower odds of being in the lowest S-titer quartile (OR0.206, p<0.001). Odds for S-antibody seroconversion with anti-TNF were higher compared to rituximab both for patients in G2 (OR26.3, p<0.001) and G3 (OR27.5, p<0.001).
Patients who received 2 boosters (G4) all had S-seroconversion and no IMID treatment modality was associated with higher odds of being in the lowest quartile.
After baseline vaccination (G2) smokers had higher risk of being in the lowest S-antibody titer quartile (RR1.45, p=0.0098). This observation persisted after 1 booster (G3)(RR1.42, p=0.0122) but was no longer noticed after 2 boosters (G4).
After start of booster vaccinations, 25.17% of patients had experienced IMID flare-up in the previous months. No significant association between IMID flare-up rate and previous SARS-CoV2 infection was found. There was no increased risk of IMID flare-up with additional booster vaccination. However, patients who received 2 booster vaccines showed a lower RR for IMID flare-up compared to those who only received 1 booster (RR0.70, p=0.0067).

	G1 (N: 2144)	G2 (N: 1532)	G3 (N: 1283)	Group 4 (N: 147)	Group 5 (N: 40)
Mean age (SD)	44.6 (35.5)	46.9 (30.8)	46.6 (32.7)	51.0 (15.7)	39.4 (14.4)
Male/female	1088 (51.0%)/1047 (49.0%)	794 (51.9%)/737 (48.1%)	661 (51.6%)/621 (48.4%)	80 (54.4%)/67 (45.6%)	24 (60.0%)/16 (40%)
Active smoker	369 (17.2%)	261 (17.0%)	201 (15.7%)	24 (16.3%)	12 (30.0%)
TIMT (targeted treatment)	1580 (73.7%)	1232 (80.4%)	1073 (83.6%)	119 (81.0%)	38 (95.0%)
IMM (immunomodulator)	456 (21.3%)	311 (20.3%)	225 (17.5%)	39 (26.5%)	8 (20.0%)
IMM+TIMT combined	263 (12.3%)	197 (12.9%)	152 (11.8%)	24 (16.3%)	8 (20.0%)
Recent systemic steroids	229 (10.7%)	91 (5.94%)	59 (4.60%)	6 (4.08%)	4 (10.0%)

Conclusion

Certain immune-modulating treatment modalities and smoking may blunt serologic COVID19 vaccination responses. However, this is overcome by repeated booster vaccination without increased risk of IMID flare-up.

Disclosure

The BELCOMID study group received research grants from following pharmaceutical companies: Almirall, Roche, Janssen, Pfizer, Eli Lilly, Amgen, Biogen, Mylan, LEO Pharma. These companies had no role in study design, conduct nor reporting of results.

Introduction

Intestinal ultrasound (IUS) has proven to be a valuable tool for accurately detecting intestinal damage and characterizing disease behavior in Crohn’s disease (CD). IUS scoring systems for CD activity have been developed, however all the studies had methodological flaws. Therefore, studies comparing and validating the existing IUS scores in CD patients are required.

Aims & Methods

In this study, we aimed to compare two main existing scores, Bowel Ultrasound Score (BUSS) and International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) in patients with ileal CD using the simplified endoscopic activity score for CD (SES-CD).
An observational cross-sectional study was performed to evaluate the disease activity in adult CD patients with ileal involvement between November 2019 and February 2024. All patients had undergone ileocolonoscopy and IUS, the time interval between the two procedures was lower than 10 days. Receiver operating characteristic (ROC) curve analyses was performed for BUSS and IBUS-SAS to predict SES-CD ≤2 for CD.

Results

Total 56 adult patients with ileal CD were included in the study, 38 patients (67.9%) were male, the median age was 40.5 (IQR 26-46.75) years and the median duration of the disease was 8.4 (IQR, 4.93-10.29) years. In the endoscopically remission (SES-CD ≤2) group; the median BUSS was 2.63 (IQR 2.12-3.45) and the median IBUS-SAS was 14 (IQR, 11.3-18.4), while in the endoscopically active (SES-CD >2) group; the median BUSS was 5.67 (IQR, 3.47-7.76) and the median IBUS-SAS was 49.7 (IQR, 23.3-72.65). The median BUSS and median IBUS-SAS in the endoscopically remission group were significantly lower than those of the endoscopically active group (p< 0.001, for both). The cut-off value for BUSS to determine endoscopic remission (SES-CD ≤2) was 3.9 (AUC: 0.839, 95% CI: 0.737-0.941, sensitivity: 92%, specificity: 73%, p < 0.001), while the cut-off value for IBUS-SAS to establish endoscopic remission (SES-CD ≤2) was 24.4 (AUC: 0.871, 95% CI: 0.780-0.962, sensitivity: 100%, specificity: 73%, p < 0.001).
There was a very high positive correlation between BUSS and IBUS-SAS (r=0.914, p<0.001), a high positive correlation between BUSS and SES-CD (r=0.659, p<0.001), a moderate positive correlation between BUSS and CRP (r=0.577, p<0.001). There was a high positive correlation between IBUS-SAS and SES-CD as well as IBUS-SAS and CRP (r=0.728, p<0.001 and r=0.657, p<0.001 respectively).

Conclusion

In this study, we found that the most accurate cut-off value for BUSS was 3.9 and the most accurate cut-off value for IBUS-SAS was 24.4 in CD patients with endoscopic remission (SES-CD ≤2) group. Also, we have confirmed that both BUSS and IBUS-SAS significantly correlate with endoscopic activity in a real-world cohort.

Introduction

Perianal fistulising Crohn’s disease (PFCD) affects up to 20% of patients with Crohn’s Disease (CD). PFCD can cause pain, purulent discharge and faecal incontinence, leading to significant morbidity and reduction in quality of life. The use of biologic therapy, antibiotics and surgical intervention remain the mainstay of management of perianal fistulas.

Aims & Methods

This study aims to review current practices in the management of PFCD across two large tertiary IBD centres. This retrospective cohort study assessed adult patients with PFCD between two tertiary Australian hospitals between 2006 to 2024. Patients with PFCD were identified using prescribing data. CD phenotype, therapy and fistula-related data were extracted. Biologic choice and therapeutic drug monitoring, antibiotic choice and duration, surgical intervention, and length of stay in hospital were monitored. Cross-sectional disease activity of perianal fistulizing disease was assessed at the time of data collection using clinical fistula symptom grade and radiological assessment were available. Clinical remission was defined as fistula symptom grade of 1 or less. Radiological remission was defined by healing fistula tracts or no active inflammation seen on MRI. The study was approved by the Central Adelaide Local Health Network Human Research Ethics Committee (HREC19145).

Results

Gender Male, n Female, n Age, y, median (IQR)	n = 57 30 27 40 (31-54)
Active Smoker, n (%)	14 (24.5)
Median length of clinical follow up, months, n (IQR)	46.5 (23.8-72.3)
Antibiotics Prescribed Metronidazole, n treated (%) Amoxicillin / Clavulanic acid, n treated (%) Others, n treated (%)	47 (68.1) 13 (27.7) 9 (4.2)
Duration of Antibiotics Metronidazole, median duration, days (IQR) Amoxicillin / Clavulanic acid, median duration, days (IQR) Others, median duration, days (IQR)	5 (5-7) 5 (5-10) 14 (7-14)
Biologic therapy Total patients on biologic therapy, n (%) Infliximab, n (%) Adalulimab, n (%) Ustekinumab, n (%)	56 (98.2) 43 (75.4) 11 (19.3) 2 (3.5)
Therapeutic Drug Monitoring (Infliximab) Infliximab level performed, n (%) Subtherapeutic (Infliximab level <10), n (%) Active disease and subtherapeutic (Infliximab level <10), n (%)	37 (86%) 30 (81.1%) 12 (40%)
Remission status Clinical Remission, n (%) - Defined as Fistula symptom grade of 1 or less Radiological Remission, n (%) - Defined as healing fistula tracts or no active inflammation seen on MRI	48 (84.2) 33 (57.8)
Subtherapeutic Therapeutic Drug Monitoring (All biologic agents) In Remission, n (%) Active Disease, n (%)	18 (56.2) 14 (43.8)

Table 1. Baseline characteristics

57 patients (median age, 40 years (31-54); 52.6% male) with PFCD were included in the study and followed over a median duration of 46.5 months (23.8-72.3). There were a total of 157 individual surgical procedures over the period, 2.75 per patient, most of which (94.2%) were examination under anaesthesia. Antibiotic therapy was dispensed for either perianal sepsis or an actively draining fistula in 26 patients, 2.65 number of courses per patient. The most common antibiotic prescribed was Metronidazole (68.1%), followed by Amoxicillin / Clavulanic acid (27.7%). The median duration of antibiotic therapy was 5 days (5-7) for Metronidazole and 5 days (5-10) for Amoxicillin / Clavulanic acid. There were 56 (98.2%) patients on biologic therapy. The most common biologic agent was Infliximab (75.4%), followed by Adalimumab (19.3%) and Ustekinumab (3.5%). At the time of analysis, 48 patients (84.2%) were in clinical remission and 33 patients (57.8%) were in radiographical remission. In patients treated with infliximab, 37/43 (86%) had therapeutic drug monitoring performed. Amongst these, 30 (81.1%) had subtherapeutic levels (defined as Infliximab level < 10), with 12/30 (40%) of patients having active PFCD.

Conclusion

Across two tertiary IBD centres, management of PFCD is variable and not in keeping with current guidelines. Short courses of antibiotic therapy were used, and the majority of patients had subtherapeutic drug levels when tested. Optimising outcomes for patients with PFCD requires awareness of best practice and a multidisciplinary team approach.

Introduction

Etrasimod is an oral, once-daily, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC).

Aims & Methods

This post hoc analysis of ELEVATE UC 52 and ELEVATE UC 12 describes etrasimod efficacy and safety in patients stratified according to baseline disease activity. In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), patients aged 16–80 years with moderately to severely active UC were randomised 2:1 to etrasimod 2 mg once daily or placebo.¹ ELEVATE UC 52 had a treat-through design comprising a 12-week (wk) induction period followed by a 40-wk maintenance period. ELEVATE UC 12 comprised a 12-wk induction period. In this analysis, data were pooled from both trials and patients’ baseline UC activity was stratified as moderately or severely active based on a Modified Mayo score (MMS) of 5–7 or 8–9, respectively. Efficacy endpoints were measured at Wk 12 and included mean percentage change from baseline in MMS and clinical response/remission according to MMS category. Efficacy data were analysed descriptively, and 95% confidence intervals (CIs) were calculated for all means or proportions using normal approximation or simultaneous estimation method, respectively. Safety was assessed up to Wk 52 in the pooled safety analysis set.

Results

Of the 743 patients in this analysis, 525 (70.7%) had a baseline MMS 5–7 and 218 (29.3%) had a baseline MMS 8–9. Baseline characteristics were broadly similar between subgroups, with the exception of lower rates of proctitis in patients with MMS 8–9 vs 5–7 (3.3% and 3.0% vs 9.3% and 9.4% in etrasimod and placebo groups, respectively). At Wk 12, patients treated with etrasimod showed larger mean percentage reductions (95% CI) in MMS, vs placebo, regardless of baseline disease activity (48.4% [52.3, 44.4] vs 27.0% [32.2, 21.7] for baseline MMS 5–7, and 46.4% [51.2, 41.5] vs 29.8% [37.2, 22.3] for baseline MMS 8–9). At Wk 12, more patients treated with etrasimod achieved clinical response, vs placebo, regardless of baseline disease activity, with an overall reduction from baseline disease activity as measured by MMS categorisation in both baseline MMS subgroups (Table). Generally, rates of treatment-emergent adverse events (TEAEs) were similar across treatment and baseline disease activity subgroups (proportion of patients with any TEAE: 59.0% vs 50.8% and 65.1% vs 56.1% for etrasimod vs placebo, in baseline MMS 5–7 and 8–9 groups, respectively).

Table. Proportion of patients achieving clinical response and each MMS category at Wk 12 stratified according to baseline disease activity (pooled data from ELEVATE UC 52 and ELEVATE UC 12)
	Baseline MMS 5–7 (moderate)		Baseline MMS 8–9 (severe)
	Placebo QD (N=181)	Etrasimod 2 mg QD (N=344)	Placebo QD (N=66)	Etrasimod 2 mg QD (N=152)
Clinical response,a % (95% CI)b	39.8 (32.6, 46.9)	61.3 (56.2, 66.5)	30.3 (19.2, 41.4)	64.5 (56.9, 72.1)
MMS category, % (95% CI)c
Remission (MMS 0–2) Mild (MMS 3–4) Moderate (MMS 5–7) Severe (MMS 8–9) MMS not availabled	17.1 (11.1, 25.5) 26.0 (18.5, 35.1) 35.4 (26.9, 44.9) 8.3 (4.4, 15.2) 13.3 (8.1, 21.1)	38.4 (31.9, 45.3) 24.4 (19.0, 30.8) 23.0 (17.7, 29.3) 2.6 (1.1, 5.9) 11.6 (7.9, 16.8)	10.6 (4.2, 24.2) 15.2 (7.0, 29.6) 37.9 (24.3, 53.7) 24.2 (13.4, 39.8) 12.1 (5.1, 26.0)	21.7 (14.4, 31.4) 25.7 (17.7, 35.7) 30.3 (21.7, 40.5) 13.2 (7.6, 21.8) 9.2 (4.8, 17.1)
aClinical response was defined as a ≥2-point and ≥30% decrease from baseline in MMS, and a ≥1-point decrease from baseline in RBS or an absolute RBS ≤1. b95% CI is based on normal approximation to binomial proportion. c95% CI was calculated using the Goodman method of simultaneous CI estimation. dMMS was not available for some patients at Wk 12 for various reasons, including discontinuation prior to Wk 12. CI, confidence interval; MMS, Modified Mayo score; N, number of patients in the baseline disease activity subgroup by treatment; QD, once daily; RBS, rectal bleeding subscore; UC, ulcerative colitis.

Conclusion

Etrasimod showed greater reductions in disease severity and higher rates of clinical response, vs placebo, regardless of baseline disease activity. The safety profile of etrasimod was consistent with the overall trial population¹ and was not impacted by baseline disease activity.

References

1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171

Disclosure

BES has received consulting fees from AbbVie, Abivax, Alimentiv, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Morphic Therapeutics, MRM Health, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Sun Pharma, Surrozen, Takeda, Target RWE, Teva, Theravance Biopharma, TLL Pharmaceutical, Ventyx Biosciences; speaker fees from Abivax, Bristol Myers Squibb, Janssen, Lilly, Pfizer, Takeda; research grants from Bristol Myers Squibb, Janssen, Pfizer, Takeda, Theravance Biopharma; stock options from Ventyx Biopharma; and other support from Bristol Myers Squibb, Lilly, Janssen, Pfizer and Takeda. MCD is a consultant for AbbVie, Abivax, AstraZeneca, Bristol Myers Squibb, Janssen, Lilly, Merck, Pfizer Inc, Prometheus Labs, Spyre and Takeda. PGK has received consulting and speaker fees from AbbVie, Janssen, Pfizer Inc, and Takeda and has received scientific grants from Pfizer Inc and Takeda. SV has received speaker fees from AbbVie, Dr. Falk Pharma, Ferring, Galapagos, Hospira, Janssen, MSD, Takeda, and Tillotts; consultancy/advisory fees from AbbVie, AbolerIS Pharma, Alimentiv, Arena, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Dr Falk Pharma, Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, Johnson and Johnson, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer Inc, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillots Pharma AG and Zealand Pharma; and grant/research support from AbbVie, MSD, Pfizer Inc, Galapagos, Janssen and Takeda. RP has received consulting fees 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, Theravance Biopharma, Trellus, Viatris, Ventyx, UCB; speaker fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda; an advisory board member for AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda, Ventyx; and received research support from AbbVie, Janssen, Takeda and Pfizer. MDL is a consultant for AbbVie, Janssen, Pfizer Inc, Takeda, BMS, Target PharmaSolutions, Prometheus, Lilly, Salix, Valeant, Genentech, Roche, Calibr, Theravance; and has received research support from Pfizer Inc and Takeda. JCW, JW and EB are employees and shareholders of Pfizer Inc. AM is an employee of Pfizer Ltd and shareholder of Pfizer Inc. MG is an employee and shareholder of Pfizer AG. AJY has received consultancy fees from AbbVie, Pfizer Inc, Arena, Takeda, Bristol Myers Squibb; and speaker fees from Bristol Myers Squibb.