Introduction

Data are needed to inform therapeutic positioning of advanced therapies, including biological drugs, small molecule agents, and stem cells for fistulizing Crohn’s disease (CD).

Aims & Methods

We aimed to assess the comparative efficacy of these advanced therapies in patients with fistulizing CD. We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials between inception and March 21st, 2023. The co-primary outcomes were induction of fistula remission, defined as closure of all draining fistulas at week 6-14 and week 44-54. Network meta-analysis was conducted under the Bayesian framework.

Results

We identified a total of 1,275 citations, of which 21 randomized clinical trials comprising 1,452 patients were eligible and included in the analysis. Based on the probability of achieving fistula remission within the induction period (week 6-14), infliximab 5 mg/kg monotherapy or in combination with ciprofloxacin ranked highest but was not statistically superior to other advanced therapies. Further, upadacitinib 45 mg once daily, infliximab 10 mg/kg, and ustekinumab 6 mg/kg were similarly superior to placebo, while adipose-derived stem cells Cx401, bone marrow-derived mesenchymal stem cells, vedolizumab 300 mg, and adalimumab 80/40 mg were not superior to placebo. Based on the probability of inducing long-term fistula remission during the maintenance period (week 44-56), upadacitinib 30 mg or 15 mg ranked highest although not superior to placebo; of note, both doses of upadacitinib did achieve statistical significance in terms of superiority to placebo for fistula remission at week 52 in the original trial. In contrast, adalimumab 80/40 mg, infliximab 5 mg/kg and adipose-derived stem cells Cx601 were superior to placebo but no differences between the active interventions were demonstrated.
Table 1: League plot for the comparison of advanced therapies in patients with fistulizing Crohn’s disease for maintenance of fistula remission at weeks 44-56. The values in each cell represent the relative treatment effect (relative risk and 95% credible intervals) of the column-defining treatment compared to the row-defining treatment. A double asterisk indicates statistical significance.

Conclusion

We found no apparent differences in efficacy between currently available advanced therapies for fistulizing CD. The study supports the role of infliximab 5 mg/kg, upadacitinib 45 mg, ustekinumab 6 mg/kg, and adipose-derived stem cells in the clinical management of fistulizing CD. The current study informs the positioning of advanced therapies; however, clinical decisions need to be individualized.

Disclosure

M.A.: None
D.N.R.: None
F.B.: Personal fees from Tillotts Pharma, outside the submitted work.
J.B.: reports grants and personal fees from AbbVie, grants and personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillotts Pharma, personal fees from Samsung Bioepis, grants, and personal fees from Bristol Myers Squibb, grants from Novo Nordisk, personal fees from Pharmacosmos, personal fees from Ferring, personal fees from Galapagos, outside the submitted work.
J.B.S.: has received research grants from Takeda, Janssen and is national coordinator of studies from AbbVie, Arena Pharmaceuticals, Ely Lilly, and Boehringer Ingelheim. None of these pertain to the research submitted here.

Introduction

Inflammatory bowel disease (IBD) is a significant risk factor for the development of Avoidant/Restrictive Food Intake Disorder (ARFID). ARFID is an eating disorder characterized by restrictive food intake, accompanied by at least one of the following: significant weight loss, nutritional deficiencies, dependence on enteral feeding or supplementation, or marked psychosocial impairment.

Aims & Methods

Objective: To assess the presence of ARFID and its impact on body composition and quality of life in patients with IBD. Methodology: This cross-sectional study included 105 outpatients diagnosed with IBD. The Nine Item ARFID Screen (NIAS) was used to assess ARFID symptoms, and quality of life was measured using the Inflammatory Bowel Disease Questionnaire (IBDQ). Body composition was evaluated through anthropometric measurements, bioelectrical impedance analysis, and handgrip strength testing.

Results

The study included 61 patients with ulcerative colitis and 44 with Crohn’s disease, with a mean age of 41.5 ± 15.11 years; 70% were female, and the mean disease duration was 11.19 ± 7.58 years. Regarding disease activity, 27% had clinical activity and 45% had endoscopic activity. Overall, 23% of patients were classified as having ARFID symptoms, and 35% scored ARFID subtype 3, which is associated with gastrointestinal-related food avoidance. The mean BMI was 25.92 ± 5.18 kg/m², with 52.38% classified as overweight. The mean body fat percentage by skinfold measurement was 28.47 ± 7.5%, with 8% of individuals below average. Bioimpedance analysis showed that 86.41% had low muscle mass, and the mean handgrip strength was 27.37 ± 8.67 kgf, with 7% of participants having inadequate strength. The mean total IBDQ score was 141.29 ± 47.68 points. ARFID classification was associated with lower quality of life, as reflected by the total IBDQ score (p = 0.0078) and its gastrointestinal (p = 0.0022), systemic (p = 0.0138), and social (p = 0.0194) subdomains. It was also correlated with lower BMI (p = 0.0206) and lower body fat percentage (p = 0.0045). However, no correlation was found with muscle mass (p = 0.2969).

Conclusion

ARFID symptoms are common in patients with IBD, likely due to prolonged dietary restrictions during active disease and maintained during remission, potentially impacting both nutritional status and quality of life. Despite this, there is a scarcity of research on this topic, particularly among IBD patients. Further studies are needed to explore how the restriction of various food groups affects nutritional, psychosocial, and quality of life outcomes in this population.

References

BISCHOFF S C; BAGER, P; ESCHER, J; et al., ESPEN guideline on Clinical Nutrition in inflammatory bowel disease. Clinical Nutrition 42 (2023) 352-379;
HARER K, JAGIELSKI C, RIEHL M, et al. Avoidant/restrictive food intake disorder among adult gastroenterology behavioral health patients: demographic and clinical characteristics. Gastroenterology 2019;156:S-53;
Diagnostic and Statistical Manual of Mental Disorders: DSM-5 - American Psychiatric Association - FIFTH EDITION. Porto Alegre : American Psychiatric Publishing; 2013;
Oligschlaeger, Y; Yadati, T;Houben, T; Condello, C M; Shiri-Sverdlov, R. Inflammatory Bowel Disease: A Stressed “Gut/Feeling”. Cells. 2019 Jul, vol. 8: 659.
PETERS, J E; BASNAYAKE, C; HEBBARD, G S; SALZBERG, M R; KAMM, M A. Prevalence of Disordered Eating in Adults with Gastrointestinal Disorders: A Systematic Review Neurogastroenterol Motil, agosto 2022;
Zia JK, Riddle M, DeCou CR. Prevalence of eating disorders, especially DSM-5’s avoidant restrictive food intake disorder, in patients with functional gastrointestinal disorders: a crosssectional online survey. Gastroenterology 2017;152:S715–S716ZICKGRAF, H F; ELLIS, J M. Initial validation of the Nine Item Avoidant/Restrictive Food Intake disorder screen (NIAS): A measure of three restrictive eating patterns. Appetite 123 (2018) 32e42.

Introduction

Dietary changes are common in individuals with inflammatory bowel disease (IBD) to manage symptoms and avoid perceived triggers. However, such adaptations may predispose patients, especially adolescents and young adults, to eating disorders (ED) and avoidant/restrictive food intake disorders (ARFID).

Aims & Methods

This cross-sectional study aimed to assess the prevalence of ED and ARFID in young adults with paediatric-onset IBD, identify associated risk factors, and examine the relationship between ED, ARFID and the risk of malnutrition. Patients previously diagnosed with IBD at <18 years of age and currently followed at two adult IBD academic centers were consecutively enrolled. Screening for ED, ARFID and malnutrition was performed. ARFID risk was assessed using the Nine Item ARFID Screen (NIAS), which evaluates picky eating, low appetite, and food-related fear, with scores >23 were indicating probable ARFID. ED risk was evaluated using the Eating Attitudes Test (EAT-26), with scores ≥20 considered positive. Malnutrition risk was assessed using the Patient-Generated Subjective Global Assessment (PG-SGA), with scores >=6 indicating malnutrition¹​

Results

A total of 144 patients were included (median age 24 years [range: 21–28]; 54.2% female), with 50.7% diagnosed with Crohn’s disease (CD). History of enteral nutrition during childhood was reported in 40.3% of patients, predominantly among those with CD (64.4%). At the time of evaluation, one-third (34.7%) of the cohort had active disease, and the median BMI was 21.8 (IQR 20.1–24.2).
ARFID risk was observed in 16.7% of patients, with food-related fear being the most prevalent domain (13.2%) with no significant association with the disease activity (37.5% vs 34.2%; p=0.46). Based on EAT-26 scores, 11.8% screened positive for ED. The PG-SGA scores correlated significantly with the NIAS scores (rho=0.56, p<0.001) but not with EAT-26 (p=0.26). Malnutrition (PG-SGA ≥6) was observed in 15.3% of the cohort and it was significantly associated with ARFID risk (p<0.001). Prior exposure to enteral nutrition was not associated with increased ARFID risk (p=0.54), but was significantly associated with a reduced risk of ED (p=0.008).

Conclusion

Young adults with pediatric-onset IBD are at risk of ARFID, especially driven by food-related fears, and, to a lesser extent, of ED. Prior exposure to enteral nutrition was not associated with increased ARFID risk, but it was associated with a reduced risk of ED, supporting its safe use in pediatric IBD management. Routine assessment for eating disorders and malnutrition risk should be standard practice in IBD care for young adults

References

1. Gabrielson DK, Scaffidi D, Leung E, et al. Use of an abridged scored Patient-Generated Subjective Global Assessment (abPG-SGA) as a nutritional screening tool for cancer patients in an outpatient setting. Nutr Cancer. 2013;65(2):234-239. doi:10.1080/01635581.2013.755554

Clinical Case Summary

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive non-Hodgkin lymphoma with poor prognosis. We present a case of colonic T-cell lymphoma diagnosed in a patient with refractory chronic diarrhoea.
A 60-year-old Chinese female with a family history of colon cancer had recurrent admissions with extensive workup for a 4-month history of chronic watery non-bloody diarrhoea and 12-kg weight loss. Initial blood tests showed normochromic normocytic anaemia and hypokalaemia. Stool studies were negative for infections but demonstrated elevated calprotectin and low elastase. Coeliac and autoimmune workup returned negative. A Computed Tomography scan showed prominent nonspecific central mesenteric abdominal nodes without pancreas or small bowel abnormalities.
Initial colonoscopy revealed a 2mm descending colon polyp and normal looking colonic mucosa. Random terminal ileum and colonic biopsies were unremarkable. Polyp histology showed focally increased intraepithelial lymphocytes insufficient to diagnose microscopic colitis.
Working differentials included pancreatic insufficiency, small intestinal bacterial overgrowth and irritable bowel syndrome. She was treated with various drugs including Rifaximin, Pancrelipase and Nortriptyline. However, her symptoms persisted with increasing stool calprotectin levels. A repeat colonoscopy performed 2 months after the initial endoscopy, showed normal colonic mucosa again. However, random colonic biopsies histology demonstrated florid intraepithelial lymphocytosis and immunohistochemistry stains confirming MEITL. Systemic chemotherapy was initiated and her diarrhoea resolved.
Though MEITL classically involves the small bowel, our case demonstrated florid colonic involvement. This patient’s indolent presentation illustrated the diagnostic pitfall of a normal looking colon during colonoscopy, raising the importance of random colonic biopsies and repeat evaluation in persistent unexplained diarrhoea.

References

Illustrative material: Endoscopic images showing normal-appearing colonic mucosa. Histological sections demonstrating intraepithelial lymphocytosis on initial colon biopsy. Subsequent biopsy on repeat colonoscopy with immunohistochemistry showing CD3, CD8, CD56, granzyme B, and TIA-1 positivity
References:
Ozaka S, Inoue K, Okajima T, et al. Monomorphic epitheliotropic intestinal T-cell lymphoma presenting as melena with long-term survival: A case report and review of literature. World J Gastroenterol. 2021;27(38):6501-6510. doi:10.3748/wjg.v27.i38.6501
Afzal A, Esmaeili A, Ibrahimi S, Farooque U, Gehrs B. Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma With Extraintestinal Areas of Peripheral T-Cell Lymphoma Involvement. Cureus. 2020;12(8):e10021. Published 2020 Aug 25. doi:10.7759/cureus.10021
Tian S, Xiao SY, Chen Q, Liu H, Ping J. Monomorphic epitheliotropic intestinal T-cell lymphoma may mimic intestinal inflammatory disorders. Int J Immunopathol Pharmacol. 2019;33:2058738419829387. doi:10.1177/2058738419829387
Shin SY. A Rare Case of Intestinal T-cell Lymphoma with Multiple Complications. JDCR 2023;11:114-118. doi.org/10.52927/jdcr.2023.11.2.114
Sun ZH, Zhou HM, Song GX, Zhou ZX, Bai L. Intestinal T-cell lymphomas: a retrospective analysis of 68 cases in China. World J Gastroenterol. 2014;20(1):296-302. doi:10.3748/wjg.v20.i1.296

Introduction

Lactose intolerance is characterized by gastrointestinal symptoms triggered by lactose ingestion and presumably related to bacterial metabolism of malabsorbed lactose which results in hydrogen (H₂) production. However, only a subset of individuals with lactose malabsorption (M+), as diagnosed by a positive H₂ breath test, develops symptoms (S+), while others exhibit symptoms (S+) without evidence of malabsorption (M-). In the past, the lack of validated symptom assessment tools has limited the ability to comprehensively assess symptom burden and evaluate mechanisms of symptom pathogenesis. This study used the validated aCPQ to quantify symptom burdens and correlate these with H₂-breath test parameters (see reference).

Aims & Methods

We analyzed 927 patients with functional gastrointestinal disorders who underwent a 50 g lactose H₂-breath test (180 min). Malabsorption (M+) was defined as a >20 ppm rise in breath H₂, and relevant symptoms (S+) as a >20 cm increase in VAS symptom scores. Symptom burdens (max score: 100 for pain, nausea, meteorism, flatulence, diarrhea) and total symptom burdens (max: 500) were calculated. Breath test parameters included maximal H₂, time to H₂ rise, and area under the curve of H₂ (AUC-H₂).

Results

Among 363 M+ participants (39% of the 928 patients), S+/M+ individuals (n =267) had a higher AUC-H₂ (9731 ± 7292 ppm·min) versus S-/M+ (n = 96; 5450 ± 5445 ppm·min, p<0.001), a shorter time to H₂ rise (58.8 ± 37.8 vs. 75.8 ± 50.7 min, p<0.01), and a steeper H₂-accumulation rate (1.67 ± 1.5 vs. 0.97 ± 1.1 ppm/min, p<0.001). S+/M+ individuals had significantly higher total symptom burdens (134 ± 96 mm VAS) compared to S+/M- (71 ± 68 mm VAS, p<0.001), and more frequently experienced multiple symptoms simultaneously. Pain (in 58% of patients), bloating (56%), and diarrhea (46%) were most prevalent in M+/S+ and significantly exceeded prevalences in M+/S- (p<0.01).

Conclusion

Lactose ingestion can elicit symptoms independently of malabsorption but malabsorbers are burdened by higher symptom severity. Symptoms of lactose intolerance in malabsorbers are associated with distinct H₂-breath test kinetics suggesting faster increase in bacterial H₂ production and more intestinal H₂ accumulation. These findings suggest a role for the colonic bacterial metabolism of malabsorbed lactose and the microbiome in lactose intolerance and underscore the need for objective diagnostic tools to diagnose and differentiate non-malabsorptive lactose-related symptom generation from malabsorptive lactose intolerance, allowing for more individualized approaches to managing lactose intolerance in the future, including therapeutic approaches addressing the intestinal microbiome.

References

Hammer J et al. Carbohydrate induced gastrointestinal symptoms: development and validation of a test-specific symptom questionnaire for an adult population, the adult Carbohydrate Perception Questionnaire aCPQ. Eur J Gastroenterol Hepatol 2021;32:171-177