Introduction

Reductions in cancer mortality rates are the result of better screening and the use of improved treatments¹. Whilst there has been a longstanding awareness of the psychological and social impact of cancer therapy, there has been little emphasis on dealing with the physical symptoms that are a frequent complication of treatment². This can include living with chronic and debilitating bowel symptoms as well as problems with sexual and urinary function³. In our hospital, over 400 patients are diagnosed and treated for colorectal cancer annually. Data suggest that up to half, depending on the treatment(s) received, will develop chronic symptoms.

Aims & Methods

A virtual telephone clinic was set up in October 2020. Patients requiring gastroenterology review were identified at follow-up by colorectal cancer nurse specialists, colorectal surgeons or oncology specialists. Patients were reviewed by a Gastroenterology Research Fellow via a telephone consultation and investigations requested following a predefined, structured checklist according to their symptoms.

Results

66 patients (30 male, 36 female), median age 71 (range 40-89) were reviewed between October 2020 to September 2022. The mean duration of symptoms was 33 months (range 4 to 108). All had been diagnosed with colorectal cancer (20 right colon, 10 left colon and 36 rectum). Previous treatment included surgery (n=31), surgery + chemotherapy (n=13), surgery + radiotherapy (n=4), surgery + radiotherapy + chemotherapy (n=13) and radiotherapy + chemotherapy (n=5).
Patients’ symptoms pre-referral and after treatment were assessed objectively using the gastrointestinal symptoms rating scale (GSRS), with a mean GSRS on referral of 25, improving to 16 following investigation and treatment. 10 different symptoms were identified in patients (loose stool (n=45), bloating/wind (n=31), frequency (n=31), urge (n=28), incontinence (n=19), constipation (n=14), abdominal/rectal pain (n=13), mucous discharge (n=6), nocturnal symptoms (n=6) and rectal bleeding (n=1)). Outcomes of investigations are shown in Table 1. The mean overall package of care cost £803.53 (range £86.83 - £1778.49) / patient.

Table 1 showing the outcomes of investigations in patients

Conclusion

In most patients referred to our specialist clinic, one or more causes for their symptoms were identified. Treatment frequently lead to a dramatic improvement in symptoms. Future recommendations include earlier recognition of patients in need of specialist referral through the use of objective questionnaires. Results from a virtual clinic are consistent with previously reported data from face-to-face consultations.

References

1. Schreuders, E.H., et al., Colorectal cancer screening: a global overview of existing programmes. Gut, 2015. 64(10): p. 1637-49.
2. Andreyev, H.J., et al., Algorithm-based management of patients with gastrointestinal symptoms in patients after pelvic radiation treatment (ORBIT): a randomised controlled trial. Lancet, 2013. 382(9910): p. 2084-92.
3. Andreyev, J., Gastrointestinal symptoms after pelvic radiotherapy: a new understanding to improve management of symptomatic patients. Lancet Oncol, 2007. 8(11): p. 1007-17.

Disclosure

There is no conflict of interest to declare.

Introduction

Precision medicine aims to expand upon the summary average treatment effects reported in clinical trials by providing more refined, individualised estimates of treatment effects. The phase IIb TUSCANY-2 study (NCT04090411), which examined the efficacy and safety of afimkibart (RO7790121/RG6631; previously PF-06480605/RVT-3101), an anti-TL1A antibody, in patients (pts) with moderate to severe ulcerative colitis (UC), previously reported clinically meaningful treatment effects at UEGW 2024.¹ Here, we report post hoc analyses of the relationship between baseline clinical characteristics and Week 14 efficacy in pts enrolled in TUSCANY-2.

Aims & Methods

Pts were randomised to receive subcutaneous afimkibart 50mg, 150mg, 450mg or matched placebo (PBO) monthly during induction. In this post hoc analysis, all afimkibart doses were pooled, and the endpoint of interest was clinical remission by modified Mayo score (mMS; defined as stool frequency subscore=0 or 1; rectal bleeding subscore=0; and endoscopic subscore [ES]=0 or 1) at Week 14. Our investigation of more patient-specific treatment effects was guided by the Predictive Approaches to Treatment effect Heterogeneity (PATH) statement.² We developed a regularised logistic regression model to predict the probability of Week 14 remission and to help examine heterogeneity of treatment effects based on the following baseline characteristics: mMS, C-reactive protein (CRP), serum albumin, Robart’s Histopathology Index (RHI), number of failed advanced therapy classes, corticosteroid use, disease extent, disease duration, age and sex. Baseline faecal calprotectin (FCP) was investigated separately due to the extent of missing data.

Results

The proportion of pts achieving clinical remission by mMS at Week 14 in the afimkibart pooled dose arm was 32.5% (65/200; 90% confidence interval [CI]: 27.3 to 38.1) compared with 13.3% (6/45; 90% CI: 7.1 to 23.8) of pts in the PBO arm (treatment delta: 19.2%; 90% CI: 7.6 to 27.9). Based on calibrated predictions from the multivariate model, all of the individual TUSCANY-2 pts (both treated with PBO and afimkibart) had anywhere between a 2–76% probability of Week 14 remission at baseline. The clinical characteristics included in the model explained ~10% of the variability in the observed outcomes. There was no evidence that the clinical characteristics were associated with heterogeneous treatment effects on the relative scale (odds ratios appeared to be constant; p-value >0.5). On the clinically meaningful absolute scale, the treatment delta in the top 50% of pts with a higher baseline probability of remission (27–76%) was 28.5% (90% CI: 8 to 42; 45.2% in afimkibart pooled dose arm vs 16.7%, in PBO arm), compared with a treatment delta of 7.6% (90% CI: –7 to 18; 18.8% in afimkibart pooled dose arm vs 11.1%, in PBO arm) in pts with a lower baseline probability of remission (2–27%). Lower baseline CRP, lower RHI and higher serum albumin contributed to a greater probability of remission and absolute benefit from treatment with afimkibart.

Conclusion

Pts with inflammatory bowel disease (IBD) have diverse baseline characteristics that are associated with variability of treatment outcomes, yet clinicians rely on reported averages from clinical trials to make individual treatment decisions. This analysis demonstrates how precision medicine approaches, that account for diverse characteristics, may improve interpretation of positive IBD clinical trial results. Integrating genetic and novel biomarkers alongside clinical features could help to better predict individual outcomes for pts with IBD.

References

1. Danese S, et al. Presented at UEGW 2024 (Oral presentation OP079).
2. Kent D, et al. The Predictive Approaches to Treatment effect Heterogeneity (PATH) Statement. Ann Intern Med 2020;172:35–45.

Disclosure

This study was sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing support, under the direction of the authors, was provided by Victoria Dagwell, MSc, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.
LP-B reports consulting or advisory role/board from AbbVie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, Bristol Myers Squibb, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Inc., Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeutics, Pandion, Par' Immune, Pfizer, Prometheus, Protagonist, F. Hoffmann-La Roche Ltd, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx and Ysopia; speakers’ bureau from AbbVie, Alfasigma, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genentech, Inc., Gilead, Janssen, Kern Pharma, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots and Viatris. JRA reports consulting or advisory role/board from Janssen, Pfizer, AbbVie, Vedanta, Genentech, Inc., Seres Therapeutics, Ferring, GSK, Merck, Bristol Myers Squibb, Roivant, Celltrion, TRXBio and Shattuck Labs; speakers’ bureau from AbbVie and Janssen. SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Lilly, Enthera, Ferring Pharmaceuticals, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, F. Hoffmann-La Roche Ltd, Sandoz, Sublimity, Takeda, Teladoc Health, TiGenix, UCB, Vial and Vifor; lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals, Gilead, Janssen, Mylan, Pfizer and Takeda. PSD reports employment at Northwestern University; consulting or advisory role/board from AbbVie, Adiso, Alimentiv, Celltrion, Genentech/Roche, Geneoscopy, Janssen, Shattuck and Takeda; research funding from Takeda and Bristol Myers Squibb. AB reports employment and stockholder from Pfizer. DEC reports employment and stock ownership from Pfizer. EP reports employment, stock or other ownership interests and patents, royalties, other intellectual property from Pfizer. SN reports employment and stock or other ownership interests from Pfizer. MSV reports employment and shareholder from Pfizer. KH reports no conflict of interest. LU reports employment at Genentech, Inc. CS reports employment, stock or other ownership interests from Genentech/Roche. DB reports employment at F. Hoffmann-La Roche Ltd. KL reports employment and stock or other ownership interests from Genentech, Inc. BES reports honoraria for consulting from AbbVie, Adiso, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen, AstraZeneca, Biolojic Design, Biora, Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Enveda, Evommune, Ferring, Fresenius Kabi, Fzata, Galapagos, Genentech/Roche, Gilead Sciences, GSK, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microbiotica, Mitsubishi Tanabe, Mobius Care, Morphic, MRM Health, Nexus, Nimbus Discovery, Odyssey, OSE Immunotherapeutics, Palisade Bio, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist, Q32 Bio, Rasayana, Recludix, Reistone, Sanofi, Sorriso, Spyre, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union and Ventyx; consulting/speaking fees from Abivax; consulting/speaking fees/other support from Lilly; research grants/consulting/speaking fees/other support from Bristol Myers Squibb, Lilly, Janssen, Pfizer and Takeda; research grants/consulting fees from Janssen; stock/stock options from Ventyx.

Introduction

Therapeutic goals in inflammatory bowel diseases (IBD) have undergone considerable change in recent years, with a shift of focus from simply achieving clinical remission. Patient-related outcomes (PROs) have also become increasingly important as adjunctive tools in assessing the efficacy of medical therapy from the patients’ standpoint. Health-related quality of life (HRQoL) questionnaires, correlate well with disease activity and can detect meaningful clinical changes in IBD patients who either suffer a relapse of disease or achieve remission [1,2].

Aims & Methods

We aimed to assess the utility of SIBDQ in the long-term follow-up of IBD patients compared to the conventionally used markers such as clinical indices, CRP levels and endoscopic activity scores. Patients were scheduled for evaluation every 12 months, but additional evaluations were performed as required in case of worsening clinical condition. The main data collected at each study visit included clinical aspects (disease activity, on-going medication, quality of life assessement-The Short Inflammatory Bowel Disease Questionnaire), endoscopic and histological findings.

Results

In a prospective setting, 176 patients were included in the study (65 Crohn’s and 111 UC patients) , with a mean follow-up time of 16 months and 1.3 study visits per patient. Clinical activity was associated with significantly lower SIBDQ (median 4.3 vs 5.7 in those without clinical activity, p<0.001 mann whitney u) and increased inflammatory burden ( median CRP levels 1,99 mg/L vs. 7.2mg/L, p<0.001 mann whitney u). SIBDQ scores were also significantly higher in patients showing mucosal healing compared to those with active ongoing inflammation (5.8 vs 4.9, p<0.001 MWU), while inflammatory burden was also significantly different between patients with and without ongoing mucosal activity (1.6 mg/L vs 4.2 mg/L, p< 0.001 MWU). SIBDQ significantly improved over time, with a median of 4.7, 5.4 and 5.8 at visits 1, 2 and 3 respectively (p<0.001 MWU), which was also consistent with a decrease in the overall inflammatory burden in the cohort (median CRP levels of 4.2, 3.4 and 2.5 mg/L respectively).

Conclusion

Clinical activity is associated with significantly lower quality of life and increased inflammatory burden. QoL scores are significantly higher in patients showing mucosal healing compared to those with active ongoing inflammation.

References

[1] Jowett SL, Seal CJ, Barton JR, Welfare MR. The short inflammatory bowel disease questionnaire is reliable and responsive to clinically important change in ulcerative colitis. Am J Gastroenterol. 2001 Oct;96(10):2921-8.
[2] Irvine EJ^​, Zhou Q, Thompson AK.The Short Inflammatory Bowel Disease Questionnaire: a quality of life instrument for community physicians managing inflammatory bowel disease. CCRPT Investigators. Canadian Crohn's Relapse Prevention Trial. Am J Gastroenterol. 1996 Aug;91(8):1571-8.

Introduction

Hand in Hand Colon was founded to mitigate, expedite, streamline and optimize a patient's journey after undergoing a colonoscopy that unearthed a potential carcinoma. The project bridges the gaps prompted by the involvement of interdisciplinary fields from colonoscopy to diagnosis, surgery, oncological treatment and ultimately, recovery. The project, spearheaded and managed by coordinating care nurses, guides patients through the thicket of uncertainty, both bureaucratic; "where do I go now?" and emotional as patients take on the role of "cancer patient".
Services require a maze of services which can lead to miscommunications and trouble understanding and navigating through the medical system. Patients will need to wait for their biopsy results, meet with a surgeon, oncologist, or both, undergo medical imaging as well as understand what is going on around them, medical terms why they are meeting with specialists, why are they getting tests done and where all this will lead them.
Each of these steps presents the patient with obstacles: Israel's imaging availability is one of the lowest in the OECD, backed up labs, doctors work with different HMOs and available and short-wait appointments are hard to come by.
The project offers one-one-one guidance to each patient following colonoscopy with a suspicious finding by a coordinating care nurse. The nurse will guide patients through medical necessities while also presenting availability and information, supporting and easing on the overwhelmed patient.

Aims & Methods

The project is a centralizing source for the patient, working as a one stop shop: expediting results and appointments, prioritizing and clarifying medical requirements and lowering anxiety levels.
Ultimately, our goal is to achieve diagnosis early as to move forward with treatment and increase the chance of a favorable prognosis while also providing patients with the option to ask questions, understand what's going on and feel, somewhat, at ease, therefore also increasing patient responsiveness.

Results

The project began taking on patients in March 2022. The following only relates to the project at Assuta Raanana. As of January 2023, 72 patients have been referred to the site's coordinating care nurse, of them 92% have undergone expedited imagery, 46% have already undergone surgery, chemotherapy or both, 100% of biopsy analyses were submitted within two weeks and 100% of patients were contacted and offered service by the appointed nurse.
Since the project began, coordinating care nurses have participated in group sessions with expert clinicians receiving training and support on dealing with distraught patients given life changing news. Soon, nurses will also receive group sessions to work through their own emotions regarding their exposure and day-to-day work with cancer patients to manage stress, burn-out, tension and sorrow.
The nursing team works under the belief that a gastroenterological nurse's job does not begin and end with their accumulated knowledge, nursing skills, technical abilities but that these can work to adhere to the 6 C's of nursing as put forth by the NHS: care, compassion, communication, competence, courage and commitment that all come together to provide patients with the best and highest level of care possible.

Conclusion

Following our experiences during the project's first year of operation, we believe that a patient's success and overall experience can be bettered through this project.

Introduction

Patient-reported outcome measures (PROMs) are recommended for assessing patient-centered outcomes and have been suggested as a tool for quality improvement (QA), which is crucial for IBD related outcomes and as clinical trials' endpoints. Real world use of IBD PROMS as a monitoring tool that enables quick access to caregivers, is still rare. Maccabi Healthcare Services (MHS), a state-mandated healthcare provider with over 2.6 million members, emphasizes patients' cooperation in improving their health and quality of life.

Aims & Methods

Aims: 1. To implement an IBD PROMS platform according to an operational process, which triggers a response from an IBD nurse and a multidisciplinary team, for routine HMO clinical use.
2. To compare the characteristics of responders and non-responders and study immediate actions.
Methods: We have used pre-existing research on the IBD PROMS platform(1) to implement validated questionnaires (IBD control PROMIS-10 measures and general health and nutritional items). Questionnaires translated into four languages were sent every 3 months to IBD registry members (defined by EPI-IRN criteria) via text messages. The calculated results and scores are directed to the electronic medical record (EMR) and are accessible to all caregivers. Digital alerts are sent to an IBD nurse in cases of "red flags" or low scores. A steering committee designed an actionable plan defining specific nurse responses for each red flag, and whether to consult with the treating physician, dieticians or social worker. A pilot study with patients from 6 gastroenterologists included 2 rounds of PROMS. Descriptive statistics were used to compare the responders to at least one questionnaire to non-responders for demographic and clinical characteristics, as well as for immediate reactions. An automated, language-specific, personalized messaging system according to patient response was accessible to the responders, with relevant information and general recommendations.

Results

Overall participation rate of the pilot study was 137/777(17.6%). Thirty one (23%) patients had red flags and 52(38%) had sub-threshold IBD-control scores. Opening rate of the personalized messaging system was 41%. Comparison between responders and non-responders is shown in Table 1. Responders tended to be significantly older and with a higher BMI. Medical treatment including biologics was not significantly different between responders and non-responders. More disease related laboratory tests were performed among responders after their initial response.

Table 1: Characteristics of the study population and comparison between responders and non-responders (Mean ±SD, unless stated otherwise)

Conclusion

IBD PROMS has been successfully assimilated and operated at MHS EMR by a multidisciplinary team, using a supporting personalized automated platform. Significantly higher rate of disease monitoring actions such as calprotectin tests was detected for responders. Responders did not necessarily have a more active or severe disease. The response rate should be increased via robust education and training.

References

Daniel Deutscher, Clara Weil, Gabriel Chodick, Sveta Tsukinovsky, Keith Bodger, Matti Waterman, Revital Kariv. Implementing electronic patient reported outcomes in inflammatory bowel disease: patient participation, score reliability and validity.
Health Qual. Life Outcomes. 2023 Jan 13;21(1):2 ^.

Disclosure

This project is supported by Takeda pharmaceutical by a quality improvement grant