Introduction

Pfizer's Institute for Translational Equitable Medicine and our Chief Medical Officer, Aida Habtezion, MD, hosted an IBD Health Equity Summit at DDW 2023 in Chicago, Illinois on May 5, 2023 with a group of 22 key opinion leaders in the gastroenterology field. The purpose of the Summit was to uncover health equity research gaps and quality of care gaps that will enable Pfizer and our partners to determine future directions in IBD research and contribute to achieving healthcare equity by providing opportunities to improve patient outcomes, as well as address practice-based disparities.

Aims & Methods

A full day Summit was designed and developed, bringing together thought leaders and experts (representing research, HCPs and patients) to discuss health disparity gaps and possible solutions. The day was split into two parts: a morning session focused on research, with IBD researchers presenting different facets of the research construct with follow-on discussion with the audience. The afternoon was dedicated to clinical care and also included IBD experts addressing Health Equity concerns and opportunities. A follow-on summary report was developed, distributed and serves as the basis for current and future strategies aimed at closing disparity gaps among IBD patients.

Results

Several overarching themes emerged, highlighting IBD as a global affliction, and challenges that transcend geographical borders. Addressing these challenges will require solutions tailored to local and regional contexts that consider factors such as race, ethnicity, socio-economic status, culture, diets, and sexual orientations. It was also recognized that many of the challenges posed by IBD are not unique to this disease, and that valuable insights can be gained by examining other complex disease states to improve the quality of care and address health disparities in patients with IBD.

Conclusion

IBD Research
Key gaps include low clinical trial participation of patients from diverse communities due to lack of healthcare literacy, low historical representation, bias in recruitment, lack of diversity in providers.
Strategies to address these gaps include improving health literacy, workforce development and educating providers, adequate compensation for time, flexibility for participating in trials, and incorporation of digital health tools for follow-ups.
Clinical Care
There are groups of patients in several regions that lack any care, and addressing healthcare disparities in IBD care for these patients cannot be done online but will need to be done on a local and regional level on the ground.
When addressing health inequities, the heterogeneities within underserved populations like Black and Hispanic patients need to be considered.
Gaps in data on the effectiveness of therapies in specific patient populations (ie, response to anti-TNFs in black patients and patients with comorbidities).
Sponsorship is lacking to establish efforts in underserved communities on a global level; There is an opportunity to provide connection for minority physicians to resources.
By identifying gaps and potential strategies to close them, the participants have provided Pfizer and our partners a roadmap to address health disparities among IBD patients worldwide. These data and information have served as the basis for a go-forward plan to support and invest in change initiatives to close gaps. Our desire is to enlist additional partners and collaborators through a Call to Action to identify solutions at the local level that can accelerate improved IBD care and outcomes for some of the most vulnerable populations in the world.

Disclosure

Employee of Pfizer Inc

Introduction

Long-term data on bowel urgency (BU) in Crohn’s disease (CD) are limited, and the associations with other efficacy outcomes are not well studied.

Aims & Methods

Our aims were to examine the long-term efficacy of mirikizumab (MIRI) on BU remission and the associations between BU remission and clinical remission, endoscopic remission, and patient-reported outcomes (PRO) improvement at week (W) 104 in patients with moderately to severely active CD who were randomized to MIRI in the Phase 3 study VIVID-1 and continued into the long-term extension study VIVID-2. In VIVID-1, the MIRI group received induction with 900 mg intravenously (IV) at W0, W4, and W8, then 300 mg subcutaneously (SC) every 4W. W52 endoscopic responders (≥50% reduction from baseline in Simple Endoscopic Score for CD [SES-CD]) continued MIRI SC dosing in VIVID-2. Endoscopic non-responders received reinduction with MIRI IV (3x Q4W) at the start of VIVID-2 followed by SC dosing (IV-SC) as described. Patients that had an Urgency Numeric Rating Scale (UNRS) ≥3 (least to worst range 0-10) at baseline were included in these analyses. BU remission was defined as an UNRS score of ≤2. Associations between BU remission with clinical remission by Crohn’s Disease Activity Index (CDAI), endoscopic remission, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (range 0-52, higher is better), and Inflammatory Bowel Disease Questionnaire (IBDQ) remission, were assessed at W104, within the VIVID-1 W52 endoscopic response subgroups as well as the MIRI total group. Discontinuations or missing data were handled using modified non-responder imputation (mNRI) for categorical data. Missing values were imputed by multiple imputation and modified baseline observation carried forward for FACIT-Fatigue change from baseline.

Results

Over 50% of the MIRI total group, 56% of MIRI W52 endoscopic responders, and 43% of the MIRI W52 endoscopic non-responders achieved BU remission at W104. In the MIRI total group, a significantly higher percentage of patients achieved clinical remission, endoscopic remission and IBDQ remission at W104 in the BU remission group compared to those without BU remission. The improvement in fatigue by FACIT-Fatigue score was significantly more in the group with BU remission versus those without BU remission (p<0.0001). In both MIRI W52 endoscopic responders and non-responders, patients who achieved BU remission at W104, compared to those who did not, achieved significantly higher rates of clinical remission, greater improvements in FACIT-Fatigue, and higher rates of quality of life improvement measured by IBDQ remission (Table 1).

Table 1

Conclusion

Over 50% of patients with CD achieved BU remission at 2 years of treatment with MIRI. These results highlight that the achievement of BU remission corresponded with improvements to outcomes important to patients with CD, underscoring the importance of long-term management of BU in improving overall patient outcomes.

Disclosure

SRV: has received consulting fees, speaker’s honoraria and unrestricted research grants from Abbott, Alfasigma, Amgen, Arenapharm, BMS, Falk Pharma GmbH, Ferring Pharmaceuticals, Gilead, iQuone, Janssen, MSD, Permamed, Pfizer, Sanofi-Aventis, Schwabe Pharma, Takeda, Tillotts, UCB and Vifor
DTR: receives grants or contracts from Takeda, and discloses consultancy fees with AbbVie, Altrubio, Apex, Avalo Therapeutics, Bristol Myers Squibb, Buhlmann Diagnostics Corp, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Janssen Pharmaceuticals, Lilly, Pfizer, Samsung Neurologica, and Takeda. He serves on the Board of Directors for Cornerstones Health.
JW, GY, AV, REM, and RRH: Employees and stockholders of Eli Lilly.
GD-H: Has received research grants from: Alimentiv BV, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, and Takeda; and consulting fees from: AbbVie, Alimentiv, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, GSK, Merck Sharp & Dohme, Pfizer, Sorriso Pharmaceuticals, Takeda, Tillotts Pharma AG, and Ventyx Biosciences
ST: has received grants from: AbbVie, BUHLMANN Diagnostics, ECCO, Eli Lilly and Company, Ferring Pharmaceuticals, International Organization for the Study of Inflammatory Bowel Disease, Janssen, Merck Sharp & Dohme, Norman Collison Foundation, Pfizer, Procter & Gamble, Schering-Plough, Takeda, UCB Pharma, Vifor Pharma, and Warner Chilcott; and reports other disclosures from: Abacus Pharma, AbbVie, Actial Farmaceutica, ai4gi, Alcimed, Allergan, Amgen, Aptel, Arena Pharmaceuticals, Asahi Kasei Pharma, Aspen Pharmacare, Astellas, AstraZeneca, Atlantic Pharmaceuticals, Barco, Biocare Medical, Biogen, BL Pharma, Boehringer Ingelheim, Bristol Myers Squibb, BUHLMANN Diagnostics, Calcico Therapeutics, Celgene, Cellerix, Cerimon Pharmaceuticals, ChemoCentryx, Chiesi, Cisbio, Comcast, Coronado Biosciences, Cosmo Pharmaceuticals, Dr. Falk Pharma, Ducentis BioTherapeutics, Dynavax Technologies, Elan Pharma, Eli Lilly and Company, Enterome, Equillium, Ferring Pharmaceuticals, Galapagos NV, Genentech/Roche, Genzyme, Gilead Sciences, GlaxoSmithKline, Glenmark Pharmaceuticals, Grünenthal, GW Pharmaceuticals, Immunocore, Indigo Biosciences, Janssen, Lexicon Pharmaceuticals, Medarex, MedTrix, Merck, Merrimack Pharmaceuticals, Mestag Therapeutics, Millennium Pharmaceuticals, Neovacs, Novartis, Novo Nordisk, NPS Pharmaceuticals/Nycomed, Ocera Therapeutics, OPTIMA Pharma, Origin Pharma, Otsuka, Palau Pharma, Pentax Medical, Pfizer, PharmaVentures, Phesi, Phillips Pharma Group, Procter & Gamble, Pronota, Proximagen, Resolute Pharma, Robarts Clinical Trials, Sandoz, Santarus, Satisfai Health, Sensyne Health, Shire, Sigmoid Pharma, Sorriso Pharmaceuticals, Souffinez, SynDermix, Synthon, Takeda, Theravance Biopharma, TiGenix, Tillotts Pharma AG, Topivert, Trino Therapeutics with Wellcome Trust, TxCell SA, UCB Pharma, Vertex Pharma, VHsquared, Vifor Pharma, Warner Chilcott, and Zeria Pharmaceutical
AW: reports consulting and/or speaking fees from Abbvie, Bristol-Myers Squibb, Ferring, Galapagos, Janssen, Pfizer, and Takeda.

Clinical Case Summary

A 67 years old male patient had orotracheal intubation due to COVID-19 infection and respiratory insufficiency. This led to the onset of a tracheoesophageal fistula (caused by the continuous overpressure of the cuff). At admission to our Hospital, the patient was in poor clinical condition and was sent to the intensive care unit. At endoscopy, a 30 mm fistula was found.
After a first multidisciplinary evaluation, surgical treatment was attempted, but this was unsuccessful in the closure of the fistula.
In second place endoscopic suturing with Apollo Overstitch was done (double-channel gastroscope), but also this was unsuccessful in completely closing the fistula and was repeated after 5 days. On the control endoscopy after 3 days, the fistula was still there
A multidisciplinary team composed of endoscopists, anesthesiologists, bronchoscopists, and cardiologists discussed the case again. The decision was to place an Amplatzer atrial septal occluder to close the fistula (Abbott, Illinois, USA). The procedure was technically and clinically successful, and the fistula was finally closed. The patient was weaned off from intubation and then O2 therapy and was discharged after a long rehabilitation.
The stent remained in place. The patient could eat and breathe without difficulty. At 12 months follow-up the patient is completely autonomous, eats everything and is in excellent clinical condition.

Introduction

Barrett’s mucosal neoplasia can be endoscopically cured with minimal risk of lymph node metastasis while submucosally invasive neoplasia poses higher risk and usually requires surgery. Endoscopic optical diagnosis is often challenging to differentiate between the two. We aim to develop an artificial intelligence (AI) system using a deep neural network to stage Barrett’s neoplasia into mucosal (LGD, HGD, pT1a) and submucosally invasive (pT1b) lesions.

Aims & Methods

A VGG16-based deep neural network was used for the staging AI system. The model was trained with 69 images which were carefully selected from 79,159 frame images with histological ground truth. As a pre-trained model for training, the model from initial Barrett’s detection and delineation system was used, which was trained for 1,090,171 images from 161 Barrett's patients¹. We tested staging AI on pre-recorded images and its performance was compared to two experts who regularly perform Barrett's endoscopic resections.

Results

68 neoplastic images (white light, enhanced imaging, near focused/magnification) were used. 43 were mucosal (2 LGD, 31 HGD, 10 pT1a) and 25 were submucosal (6 pT1bSM1 and 19 pT1bSM2/3). The sensitivity, specificity and accuracy of AI were 80%, 84% and 82% while that of experts were 74%, 78% and 76% with no statistical difference (p=0.507).

Conclusion

This suggests that the staging AI system is good at differentiating submucosal neoplasia and it can perform as well as experts. It has the potential to help guide expert clinicians to decide if endoscopic resection of Barrett's neoplasia can be curative while helping non-expert to achieve more yield in targeted biopsy. However, more work is still needed to further refine and validate this staging AI model.

References

1. Mohamed Abdelrahim, Masahiro Saiko, Naoto Maeda, Ejaz Hossain, Asma Alkandari, Sharmila Subramaniam, Adolfo Parra-Blanco, Andres Sanchez-Yague, Emmanuel Coron, Alessandro Repici, Pradeep Bhandari, Development and Validation of Artificial Neural Networks Model for Detection of Barrett’s Neoplasia, a Multicenter Pragmatic Non-Randomized Trial, Gastrointestinal Endoscopy (2022)

Introduction

Gastric emptying (GE) of liquids and solids is differentially regulated. GE of liquids follows an exponential kinetic and mainly depends on fundic tone, GE of solids requires trituration by antral contractions for passage through the adequately opened pylorus into the duodenum. Adler et al. showed that liquid GE was more often delayed in systemic sclerosis patients compared with GE of solids (Rheumatology 2022), but knowledge on the association between GE of solids and liquids in dyspeptic patients, in general, is limited.

Aims & Methods

To investigate this association and the correlation of GE times with symptoms, we compared results of breath tests using 13C-acetate (13C-ABT, GE-liquids) and 13C-octanoic acid (13C-OBT, GE-solids) in consecutive dyspeptic patients undergoing both tests (Keller et al. UEG J 2021). Normal ranges at our institution for 13C-ABT are 20-35 min (T lag-liquids), for 13C-OBT 50-150 min (T ½-solids). All patients additionally answered the gastroparesis cardinal symptom index questionnaire (GCSI, Revicki APT 2003).

Results

302 patients were included (230 women, age 45.9 (31.7-59.5) yrs, median(IQR)). Median T lag-liquids was 25 (20-35) min, median T ½-solids 78 (60-104) min. T lag-liquids and T ½-solids were weakly associated (R=0.165, p=0.002). Both were indirectly correlated with age (R=-0.280, p<0.0001 and R=-0.179, p=0.0009, resp), and similar in men and women. Concordant results for both tests were achieved in 172 subjects (57.6%): Both were normal in 161 (53.3%), both showed accelerated GE in 10 (3.3%) and both delayed GE in 3 (1%) subjects. Discrepant results were observed in 128 subjects (42.4%), in the vast majority of these, one of the tests was normal, but in 7 subjects (2.3%), GE was accelerated in one test, delayed in the other. 67 patients (22.2%) had delayed GE in at least one of the tests. Only in this subgroup, GE time correlated significantly with GCSI (R=0.242, p=0.024), in particular with the nausea/vomiting subscale (p=0.009).

Conclusion

In a large group of dyspeptic patients, more than 45% had disturbances of liquid and/or solid GE. In less than 5% of the total group both tests were found to be either accelerated or delayed in the same patient. Instead, measurements of liquid and solid GE often differred. In patients with delayed GE in at least one of the tests, severity of gastroparesis symptoms was associated with GE time. Thus, measurements of liquid and solid GE may be complementary and identify patients with different pathomechanism leading to GE disturbances and symptoms.

Introduction

Chemoradiotherapy (CRT) is a standard non-surgical treatment for esophageal squamous cell carcinoma (ESCC). One of the major disadvantages of CRT is poor local control, and salvage esophagectomy is generally indicated for local failure; however, it is invasive with a high rate of postoperative complications and mortality so that patients often refused or are intolerant to salvage esophagectomy. Alternatively, photodynamic therapy (PDT) with talaporfin sodium (TS) is less invasive salvage treatment for local failure after CRT/ radiotherapy (RT) and was reported to have relatively high local complete response (L-CR) rate and few adverse events (AEs) in the short term. However, long-term outcomes of PDT with TS are unknown.

Aims & Methods

This retrospective study aimed to clarify the long-term outcomes of PDT with TS for local failure after CRT/RT for ESCC. Patients who underwent PDT with TS for histologically proven local failure of ESCC between December 2012 and December 2021 at the National Cancer Center Hospital East were enrolled. Patients with other active cancers or a prior history of PDT were excluded. Basic indication criteria of PDT were as follows: invasion depth limited to the shallow muscle layer, <1/2 of the esophageal circumference, absence of metastasis, and patient’s refusal or unsuitable physical condition for salvage surgery. We assessed L-CR rate, incidence of AEs, clinical courses after PDT, 3-year overall survival (OS), progression free survival (PFS) and major PFS (mPFS) in which major disease progression after PDT which defined as disease progression requiring more invasive treatment than repeated endoscopic treatment and death from all causes were considered as events. We also assessed pre-PDT factors associated with L-CR. L-CR was defined as no apparent residual tumor, disappearance of post-PDT ulcer and confirmation of the scar formation, and absence of cancer cells in biopsy.

Results

108 patients (92 men; median age 74 years [range, 52-88 years]) were enrolled. Patients with pre-CRT/RT cT1/ T2/ T3/ T4/ unknown were 50/ 22/ 24/ 9/ 3. Those with residual lesion/ local recurrence/ unknown were 63/ 39/ 6. Patients with pre-PDT ycT1a/ T1b/ T2 were 6/ 85/ 17. Pre-PDT median lesion size was 20 mm (range, 4-50 mm). 60 patients achieved L-CR after PDT, 41 had L-nonCR, and 7 were not evaluable. L-CR rate of PDT was 58.8% (60/101). During median follow-up of 23 months (range, 1-90 months), 39 patients (36.1%) finally had no recurrence after PDT. 18 patients, including 8 with L-nonCR after PDT and 10 with local recurrence after achieving L-CR, underwent re-endoscopic treatments alone and remained disease-free afterward. The other 44 patients had major disease progression, and 15 received salvage surgery among them. As for the lesion characteristics associated with L-CR, the lesions with <1/2 circumference and with <20 mm in size were more likely to achieve L-CR than those with ≥1/2 circumference (64.4% vs. 16.7%, P=0.003) and with ≥20 mm (80.0% vs. 45.2%, P=0.001), respectively. The 3-year OS/ PFS/ mPFS of all patients were 78.1%/ 29.8%/ 48.1%. The 3-year OS of L-CR cases was better than that of L-nonCR cases (89.3% vs. 67.7%, P=0.003). There was no grade 3 < AEs. Non-cardiac chest pain (60.2%), skin phototoxicity (4.6%), and esophageal stricture requiring balloon dilatation (4.7%) occurred.

Conclusion

PDT with TS for local failure after CRT/RT for ESCC showed the preferable long-term outcomes. Moreover, achieving local control with PDT could improve prognosis of patients even with local failure after CRT/RT.