Introduction

Angiodysplasias (AD) are the most common source of gastrointestinal (GI) bleeding of obscure origin in the elderly. In this population, GI AD often leads to red blood cell (RBC) transfusion-dependent anemia, resulting in high rate of hospitalizations and overuse of healthcare resources. Argon plasma coagulation (APC) is the standard treatment option, but it is an invasive procedure, with possible serious complications in the presence of significant comorbidities, and frequently ineffective in preventing recurrence of GI bleeding. Octreotide has been studied in this context, but currently it is not a widely recommended drug.

Aims & Methods

Aim: To evaluate the usefulness and safety of long-acting release-octreotide (LAR-OCT) in the control of bleeding from GI AD in elderly.
Methods: Retrospective study of patients diagnosed with chronic GI bleeding due to AD and treated with intramuscular LAR-OCT between January 2010 and December 2022 in a tertiary hospital was performed. Demographic and clinical data were collected. Exclusion criteria: LAR-OCT suspension before completing 6 months of treatment. Primary outcome: the presence of a normal Hb value (≥ 12g/dl) in the absence of any blood transfusions at 6 months(m) of therapy. Secondary outcomes: increase in Hb value, reduction of transfusional requirements and adverse events. Statistical analysis was performed with SPSS vs 25.0 (significance level of 0.05).

Results

Nineteen out of 23 patients completed at least 6m of LAR-OCT therapy. The mean age at diagnosis of AD was 74.2 years (62 to 89 years); 63.2% were female. The mean value of Charlson Comorbidity Index was 6.37 (estimated 10-year survival around 2%). Before starting LAR-OCT, 13 patients (68.4%) were under endovenous iron supplementation and 7 patients (36.8%) had undergone APC; 31.6% required at least 4 RBC units in the last month.
Primary outcome was achieved in 5 (21.7%) patients. There was a statistically significant increase in the Hb values in the first 6m of therapy (p=0.000). Three patients (15.8%) required RBC transfusions in this period, but only one presented with overt GI bleeding.
Only 8 patients achieved 24m of therapy, showing a statistically significant increase from initial to 24-m Hb values (p=0.012).
Twelve (52.2%) patients were under antithrombotic agents; there was a statistically significant difference between initial Hb and 6-m Hb value in this subgroup (p=0.002); between initial and 24-m values, there was an increase in the Hb value but not statistically significant (p=0.068).
Concomitant iron supplementation was performed in 13 and APC in 3 patients.
Adverse events were registered in 2 patients, leading to drug suspension in only 1 (dysrhythmia).

Conclusion

In the setting of “difficult-to-treat” patients with GI bleeding due to AD, octreotide has been proposed as an alternative therapeutic strategy. In this cohort of older patients, with a relatively low estimated 10-year survival due to its comorbidities, LAR-OCT appears to be effective in increasing Hb values while reducing the need of RBC transfusions and, therefore, the number of hospital admissions. This is particularly important in elderly patients, having a potential impact on their quality of life and on the healthcare costs associated with recurrent GI bleeding. Limitations of this study are the retrospective design, the small number of enrolled patients and the inability of analyzing the individual effect of LAR-OCT. Further studies are needed.

Clinical Case Summary

Neurological manifestations in Hepatitis E Virus (HEV) infection are rare. Even so, they constitute the most frequent extrahepatic involvement (55%). The most frequent neurological presentations are amyotrophic neuralgia, Guillain-Barré Syndrome (GBS) and meningoencephalitis.
A 58-year-old presents 2 week's progressive weakness of the lower limbs and jaundice. Blood tests show elevated liver enzymes and hyperbilirubinemia; with no signs of liver insufficiency. Serologies show positivity for HEV IgG and IgM. The patient confesses game meat (deer) consume in the prior 5 weeks.
The neurological examination reveals a general decrease in symmetrical strength, with abolished musculoskeletal reflexes. After normal CT, cerebrospinal fluid discloses albumin-cytological dissociation. The electromyogram is compatible with motor radiculopathy. Diagnosis of GBS is stablished and so, immediate iv immunoglobulins 0.4g/kg are administered for 5 days, with progressive analytical and clinical improvement.
HEV is the main cause of acute viral hepatitis in humans. Infection in endemic areas is generally related to the consumption of contaminated water. In contrast, in developed countries, sporadic cases are frequently described and linked to the consumption of animal meat (pigs, wild boars and deer). Thus, HEV is currently considered an emerging zoonosis.
Most cases are asymptomatic, with spontaneous clearance in most healthy subjects. As with any hepatitis, it frequently presents as painless jaundice and asthenia.
The association with GBS is well established. An immune-mediated mechanism has been postulated as the immediate cause. Supportive treatment with immunoglobulins, plasmapheresis, steroids and physical therapy are generally used. The use of ribavirin is reserved for acute fulminant hepatitis or chronic hepatitis cases.
The course is usually satisfactory with complete recovery around 60% of patients.

Introduction

Biological therapy in IBD patients is one of the cornerstones of treatment. For patients with loss of response while on maintenance therapy, options for dose escalation with the same agent are used to avoid switching targets, and this is done through a reinduction and dose intensification. While dose escalation is standard treatment with anti-TNF agents, current data on the efficacy of dose optimisation with ustekinumab in real life is limited.

Aims & Methods

The aim of the study is to assess the efficacy of dose optimisation (reinduction and intensification) therapy with Ustekinumab and to identify prognostic factors associated with clinical response. We performed a retrospective cohort study of patients that received dose optimisation with ustekinumab between January 2016 to July 2022. Demographic and clinical characteristics were obtained from the medical records. To assess for prognostic factors, responders and non-responders were compared using logistic regression analysis.

Results

A total of 94 patients were on ustekinumab treatment, and from these, 32 (30%) patients required dose optimisation during follow-up. The characteristics of patients included are summarized in Table 1. In 16 (50%) patients dose optimization was performed due to lack of response during the induction with Ustekinumab, the other 16 patients (50%) were intensified due to secondary failure. There were 15 (46.9%) patients in whom intravenous reinduction was performed prior to intensification. Three types of intensification were performed: 90mg subcutaneous every 4 weeks, 90mg subcutaneous every 6 weeks or 130mg intravenous every 4 weeks.
In 23 (72%) patients clinical remission was obtained after dose optimisation and were considered responders for logistic regression analysis. Extraintestinal manifestations (p=0.03) and secondary failure to Ustekinumab (p=0.049) were associated with a better response. No significant differences were observed between the type of intensification, the fact that they received prior reinduction or other demographic characteristics.

Conclusion

Dose optimization with ustekinumab is useful in clinical practice with a good response rate, specially in patients with secondary failure.

Introduction

Living with inflammatory bowel disease (IBD) affects physical, psychological and social dimensions, limiting the ability to engage in daily activities. It is a lifelong illness that mainly affects patients of working age, with a significant impact on their professional life. In fact, the maintenance and promotion of employees is one of the important social goals and can be considered as a determinants of health for IBD patients.
The aim of the study was to analyze the impact of disease on the working life among IBD patients and to characterize the breadth of challenges they experience in their workplace.

Aims & Methods

We conducted a cross-sectional study including patients followed for IBD and exercising a professional activity, over a 9-months period. We collected sociodemographic, clinico-biological and evolutionary data. Then, we performed a survey among these patients using a self-report questionnaires on employment status, IBD-related difficulties at work and sick leave.

Results

A total of 45 patients were included: 80% had Crohn disease (CD) and 20% had ulcerative colitis (UC). The mean age was 44 ± 12 years [extreme: 20-72 years], the sex-ratio M/F was 0.73 and the average of follow-up was 9 years [extreme: 1-18 years]. Civil servants represented 33% of the total population, those in the private sector 47%, and those in the liberal profession 20%. The most important socio-professional category was manual workers with 51%. Thirty-seven patients (82%) developed their disease after being employed with a mean delay of 11.8 years. The average number of working hours per week was 38.8 ± 11 hours [extreme: 9-60 hours]. The majority of the employees worked full time (85%), only seven subjects worked part-time, two of them because of their IBD. One in three patients (N=14) claimed to have been exposed to at least one harmful agent during their professional career, mainly organic solvents and chemicals. The main complaint reported by the patients during the daily exercise of the work was about physical fatigue which was omnipresent in the majority of the workers (69%). The digestive symptoms were mainly abdominal pain (53%) evaluated according to VAS with a mean intensity of 2.8 [0 - 10], subocclusive syndrome (40%), presence of diarrhea (38%), incontinence and fecal impaction (22%) which was worsened by the absence of accessible restrooms (33%). Psychological repercussions such as anxiety and depression were mentioned in 27% of cases. The average absenteeism during the last twelve months was 49.6 days [extreme: 0-240 days] and the average number of hospitalization days was 30.7 [extreme: 0-150 days]. Twenty patients (44%) claimed that they were subject to a salary restriction during their professional career because of their illness. Among the patients interrogated, a minority (5 people) had alreadỳ benefited from a contact with the occupational medicine and health service.

Conclusion

IBD has a negative impact on the working life of patients, due to uncomfortable symptoms, days of absenteeism, and unadapted workplaces, which can affect career plans, professional achievement, and income. Appropriate supports and accommodations to the workplace are needed in order to improve their working experience.

Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory and progressive fibrotic condition of the esophagus characterized by the infiltration of eosinophils into the esophageal mucosa and esophageal dysfunction. There remain limited treatment options for EoE and accordingly, a substantial unmet need for effective and safe medical therapies. Drug development in EoE has been hampered by heterogeneous placebo response rates, especially for clinical outcomes, and uncertainty regarding appropriate endpoint configurations. Accurate characterization of placebo response in EoE randomized controlled trials (RCTs) will help inform more future efficient trial designs.

Aims & Methods

To conduct a systematic review and meta-analysis to characterize symptomatic, endoscopic, and histologic placebo response rates in placebo controlled EoE RCTs.
Electronic database (CENTRAL, MEDLINE, EMBASE) searching (inception to 1 JAN 2024) identified placebo controlled RCTs evaluating medical therapies for adults with EoE. Studies were screened independently by 2 reviewers (AR and SA), and full texts were then reviewed for eligibility. The proportion of clinical, endoscopic, and histologic responders (improvement and remission) assigned to placebo were pooled using a random-effect model. The Stuart-Ord inverse double arcsine square root transformation method was used to compute 95% confidence intervals (CI) for point estimates of placebo response. Heterogeneity was evaluated using the I² method. Analyses were conducted in StatsDirect 3.3.6.

Results

A total of 25 placebo-controlled RCTs (placebo sample size range: N = 4–105) were included. The pooled proportion of patients receiving placebo who achieved clinical response was 41.0% (n = 11; 95% CI 29.7%, 52.8%) with substantial heterogeneity (I² = 74.9%%). Definitions of clinical response varied between studies. The pooled proportion for histologic remission (peak eosinophil count [PEC] ≤6 eos per high power field [hpf]) was 4.3% (n = 20; 95% CI 2.6%, 6.2%) with low heterogeneity (I² = 23.6%), while a more stringent definition of histologic remission (PEC ≤1 eos/hpf) yielded a pooled placebo remission rate of 1.3% (n = 18; 95% CI 0.5%, 2.5%) with low heterogeneity (I² = 0%). The pooled histologic improvement rate was 6.2% (n = 15; 95% CI 3.3%, 10.0%) with substantial heterogeneity (I² = 50.6%). Limited studies reported on endoscopic improvement and remission (Table 1).

Conclusion

More than 1 in 3 patients assigned to placebo in EoE RCTs will achieve clinical response (substantial heterogeneity detected), while less than 1 in 10 of these patients will achieve histologic remission (low heterogeneity detected). These findings highlight 1) the need to develop validated and responsive patient-reported outcome measures, which may be difficult due to the episodic nature of symptoms in EoE; and 2) the challenge of using a coprimary clinical and histologic outcome in EoE RCTs, given the discordance between symptoms and objective disease activity measures.

Table 1. Pooled proportion of placebo patients achieving measured outcomes in EoE studies

Disclosure

AR: No conflicts of interest
SA: No conflicts of interest
YY: No conflicts of interest
AQ: Is an employee of Alimentiv Inc.
DBO: Is an employee of Alimentiv Inc.
BGF: consulting fees from AbbVie, Abivax, Adiso, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Arena Pharma, Avoro Capital Advisors, Atomwise,, BioJamp, Biora Therapeutics, Blackbird Laboratories,Boehringer-Ingelheim, Boxer Capital, Celsius Therapeutics, Celgene/BMS, Celltrion, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, Forbion, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer Pharma, GSK, Hinge Bio, Index Pharma, Imhotex, Immunic Therapeutics, Intercept, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Klick Health, Landos Biopharma, Lenczner Slaght, LifeSci Capital, Lument AB, Mage Biologics, Mestag, Millennium, MiroBio, Monte Rose Tx, Morgan Lewis, Morphic Therapeutics, Mylan, Nexys Therapeutics, Nimbus Therapeutics, OM Pharma, OrbiMed Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics (Merck), Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Roivant/Televant, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Sobi, Spyre Therapeutics, Surrozen Inc., Sun Pharma, Synedgen, Takeda, Teva, Thelium, Tigenix, Tillotts, Triastek, TR1X Inc. Ventyx Biosciences, Zagbio, Zealand Pharma. Speaker fees from AbbVie, Janssen, Takeda.
VJ: consulting/advisory board fees from AbbVie, Alimentiv, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Anaptyis Bio, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Synedgen, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion; and speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi.
AJB: AJB received research funding from Nutricia, Thelial, Sanofi/Regeneron, SST, and Dr. Falk Pharma and received speaker and/or consulting fees from Laborie, Medtronic, BMS, Dr. Falk Pharma, Calypso Biotech, Eupraxia, Aqilion, Alimentiv, Sanofi/Regeneron, Reckitt and AstraZeneca
ESD: Research funding: Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda
Consultant: Abbott, Abbvie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Apollo, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Dr. Falk Pharma, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio
Educational grant: Allakos, Aqilion, Holoclara, Invea
CM: consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Ferring, Pfizer.