Introduction

The management of patients with inflammatory bowel disease (IBD) during the coronavirus disease 2019 (COVID-19) pandemic has been a challenge, as immunosuppressant therapies comprise the cornerstone of IBD treatment and social distancing is recommended to diminish the virus spread. The aim of this study is to investigate the impact of COVID-19 on the therapeutic decisions and management of patients with IBD.

Aims & Methods

Records from patients diagnosed with ulcerative colitis (UC), Crohn’s disease (CD) and unclassified-IBD (IBD-u), under follow-up by a single IBD center, were retrospectively screened from March 2020 to May 2021. Primary and secondary outcomes were predetermined to be changes in therapeutic decisions and monitoring respectively, during the pandemic.

Results

A total of 201 patients were included in the study [125 (62%) UC, 69 (34%) CD and 7 (3%) IBD-U]. Patients with UC were treated with 5-aminosalicylic acid [(5-ASA), 89], infliximab [(IFX), 21], combination therapy with 5-ASA and azathioprine (AZA), (11) and adalimumab [(ADA), 4)]. To avoid hospital environment, two patients under IFX (10%) switched to subcutaneous home-infusions with ADA and in eight patients treated with IFX (38%), infusion intervals increased to ten weeks (drug holiday). No complications were observed. Patients with CD were treated with IFX (39), ADA (12), vedolizumab (8), AZA (4), combination therapy with AZA or methotrexate (4) and ustekinumab (2). To avoid hospital environment, two patients under IFX (5%) switched to subcutaneous home-infusions with ADA and in 12 patients treated with IFX (30%), infusion intervals increased to ten weeks (drug holiday). One patient in clinical remission discontinued IFX and received AZA. Although a significant number of outpatient visits, endoscopic procedures and non-urgent surgeries were postponed, two patients with CD (IFX) required emergency surgery which was performed without delay. Patients’ monitoring was carried out through telemedicine (remote monitoring, intangible prescription and drug home delivery).

Conclusion

The vast majority of patients treated with biologics did not discontinue maintenance therapy and a significant number extended intravenous infusion intervals. The setting of this critical and unprecedented situation has led to significant changes in decision making in IBD management, based on patients’ preferences aiming an efficient and safer care.

Introduction

In the years to follow we anticipate a rise in the prevalence of an aging population of inflammatory bowel disease (IBD) patients and a rise in cancer incidence. We are in urgent need of data to help us manage these patients.
We therefore followed a cohort of patients from a referral oncology hospital with prior and active cancer who received biologic therapy to control their IBD.

Aims & Methods

We first recorded data regarding inflammatory bowel disease characteristics: disease type, disease duration, disease severity, previous surgery or hospitalization and received therapy: type and duration of biologic therapy, prior use of immunosuppressants. We also recorded all available data regarding cancer disease: cancer site, stage, virus related cancer, family history of cancer, smoking status and received therapy (curative surgery, chemotherapy, hormone therapy, radiotherapy, immunotherapy). We monitored outcomes of IBD (steroid free clinical remission, IBD-related surgery or hospitalization) and outcomes of cancer (recurrence free survival, progression free survival, overall survival).
A blinded oncologist was asked to retrospectively evaluate all available data regarding cancer prognosis (stage, histology, response to therapy) and to categorize patients in 3 groups: low, intermediate or high risk to recur or progress.

Results

A total of 30 patients were included, 57 % female, median age 60 years, 60% Crohn's Disease, median disease duration 9.5 years, 26% prior IBD surgery, 33% prior azathioprine use, 36% smokers. They were treated with anti-TNF therapy (n=19) anti-integrin therapy (n=8) and anti-IL 12/23 therapy (n=4). The majority (20%) of patients had a history of hematologic malignancy (lymphomas, myeloproliferative disorders, leukemias), 13% with a virus related cancer and 66% with curative surgery. Patients were classified retrospectively as 63% low risk, 13% intermediate risk and 10% high risk. Four patients ) with active cancer (2 with lung cancer and 2 with myeloproliferative disorders) continue to receive biologic therapy for IBD and oncological therapy with no signs of progression from both diseases. All but 3 patients have remained in steroid free clinical remission: 3 had IBD-related surgery. Median follow up under biologic therapy was 5.5 years: only 2 patients showed cancer recurrence: 1 patient with breast cancer developed bone metastases and finally died, and 1 patient with colon cancer developed bladder cancer and died as well. Both patients were classified as high risk.
In both patients biologic therapy was interrupted and that resulted in administration of high-dose steroids and IBD-related hospitalizations and infections (pneumonia, C Difficile colitis).

Conclusion

In this cohort of cancer patients with IBD treated with biologics and followed up for more than 5 years the risk of cancer recurrence was low and not unexpected in oncology terms.
Biologic therapy was successful in the majority of patients and kept them off surgeries and steroids for their underlying IBD. We need more smart and innovative ways to study this particular clinical scenario in the future.

Introduction

Surgery represents an important part of the therapeutic armamentarium for the treatment of IBD, and has been associated with variable effects on the psychological profile of patients with inflammatory bowel disease. However, surgical treatment is often distressingly perceived by these patients as the failure of their therapies, and can be a trigger for anguish, anxiety or depression.

Aims & Methods

The aim of this study is to describe the psychological impact of surgery on operated IBD patients.
This is a prospective descriptive monocentric study, conducted at the Department of Hepato-Gastro-Enterology and Proctology "Medicine B" CHU Ibn Sina Rabat, which collected all patients followed for IBD (Crohn's + UC) and who were operated between August 2021 and August 2023, the psychological impact and apprehension regarding surgery will be addressed in this study. Patients of both sexes who agreed to answer the questionnaire were included, and patients who refused to answer the questionnaire and complicated patients who stayed in intensive care were excluded.

Results

43 operated patients were included in our study, including 29 (67.4%) in the emergency setting and 14 (32.6%) scheduled. Mean age was 43 ± 16.17 years. The sex ratio was 1.26 (F/H=24/19). 35 patients (81.4%) were being followed for Crohn's disease and 8 patients (18.6%) for ulcerative colitis (UC), of whom 11 patients (25.5%) had a history of previous resection, and 1 patient (2.3%) was being followed for depression.
The surgical indications were GCA in 12 cases (27.9%), stenosis in 18 cases (41.8%), perforation in 1 case (2.3%), abscess in 8 cases (18.6%), and fistula in 4 cases (9.3%).
Our patients underwent ileo-caecal resection in 22 cases (51.2%), hemicolectomy in 6 patients (14%), coloproctectomy in 3 patients (7%), sub-total colectomy in 11 patients (25.6%), of whom 18 patients (41.9%) had an ostomy.
On the announcement of a possible surgical procedure, the thymic symptoms and feelings expressed by patients can be classified as follows: preoperative anxiety in 18 patients (41.9%), fear of death in 7 patients (16.3%), while 24 patients (55.8%) were indifferent.
The main anxiety-generating concern was postoperative pain in 7 patients (14%), potential complications in 7 patients (16.3%), failure of the procedure in 6 patients (14%), fear of dying in 7 patients (16.3%), and 25 patients (58.1%) expressed no anxiety.
The postoperative psychological experience was unremarkable in 37 patients (86%), 3 patients (7%) reported transient postoperative sadness and 3 patients (7%) developed postoperative depression, prompting consultation with a psychiatrist.

Conclusion

The impact of surgery in IBD patients not only concerns the body, but also has an effect on psychological well-being.
This study found that the pre-operative period induces a significant burden of anxiety in these patients, and depression in some.

Introduction

Several viral respiratory infections have been implicated in the exacerbation of immune mediated inflammatory diseases (IMID)^1-3. There has however been limited investigation and conflicted findings of the long-term outcomes in inflammatory bowel disease (IBD) following COVID-19⁴. We therefore performed a systematic review and meta-analysis of the long-term impact of SARS-CoV-2 infection on the disease course of IBD.

Aims & Methods

To understand the impact of early SARS-CoV-2 variants and to be better prepared for future variants, we aimed to carry out a meta-analysis of the available evidence. We searched MEDLINE and EMBASE for studies investigating the risk of adverse IBD-related outcomes (IBD flares, change in disease activity, change in medication, IBD-related hospitalization, and surgery) following a SARS-CoV-2 infection, compared to IBD patients without a SARS-CoV-2 infection. ROBINS-E for observational studies was used to assess the risk of bias in the included studies. We used random effects model (REM) meta-analysis to calculate pooled hazard ratios (HR) for the risk of adverse IBD outcomes following the acute phase of COVID-19 infection. Subgroup meta-analysis was carried out to assess the risk of the outcomes by IBD subtype (Crohn’s disease (CD) and ulcerative colitis (UC)). Meta-regression was undertaken to assess whether sex or duration of follow-up were significant predictors of IBD-related outcomes.

Results

A total of 3119 studies were identified of which 5 studies were eligible for inclusion after screening using the pre-defined inclusion criteria. The studies were based on cohorts from Denmark, Italy, the US, and a pan-European consortium including a total of 34,977 SARS-CoV-2 positive IBD patients and 53,270 IBD patients without a recorded SARS-CoV-2 infection. Two studies were assessed as having a high risk of bias. REM meta-analysis did not show an increased risk of adverse IBD-related outcomes in IBD patients with a recorded SARS-CoV-2 infection compared to those without (HR:1.05, 95% CI:0.75-1.46) and substantial between-study heterogeneity was identified in the included studies (I2=91%, p<0.01). There was no significant difference in adverse IBD-related outcomes between CD and UC patients (CD HR: 0.91, 95% CI: 0.82-1.02; UC HR: 0.83, CI: 0.75-0.90). Following meta-regression, neither sex nor duration of follow-up were found to be significant predictors of individual study effect size.

Study	Country	Source Population	Study Period	COVID-19 cohort	Reference cohort	Summary estimates with 95% CI: type of relative estimate	Adverse IBD-outcome	ROBINS-E overall Risk of Bias (RoB)‡
Papa et al., (2022)	Italy	IBD patients from 5 Italian treatment centers	Oct 2020 -Mar 2021 (6)	95	190	0.42 (0.08- 2.15): HR	Need for therapy intensification	High RoB
Hadi et al., (2022)	USA	TriNetX (40+ US Health Care Organizations)	Jan 2020 – Mar 2021 (3)	4310	22508	1.33 (1.18-1.51): RR	Inpatient hospitalisation along with a collection of stool studies, intravenous methylprednisolone requirement or flexible sigmoidoscopy	High RoB
Hong et al., (2022)	USA	5 academic medical centers within New York's Crohn's & Colitis Organization	Feb 2020 – Dec 2021 (11)	251	251	0.84 (0.44–1.42): HR	IBD-related hospitalisation/surgery	Low RoB
Bezzio et al., (2022)	Italy	IG-IBD Italian cohort	Mar 2020 – Dec 2020(7)	219	219	1.48 (0.90-2.42): OR	Change in HBI or PMS	Some concerns
Nørgård et al., (2023)	Denmark	Danish National IBD Cohort	Mar 2020 – Jul 2022(6)	30102	30102	0.85 (0.79-0.91): IRR	Corticosteroid prescription	Some concerns
Amiot et al., (2022)	EU I-CARE cohort†	I-CARE European prospective longitudinal multicenter cohort	Apr 2020 – Dec (9)	233	5224		Change in HBI or SCCAI	Some concerns
Lukin et al., (2021)	USA	I-CARE European prospective longitudinal multicenter cohort	(6 months)	118	118		Change in HBI or PMS	Some concerns

Abbreviations: HR- Hazard Ratio, RR – Relative Risk, OR – Odds Ratio, IRR – Incidence Rate Ratio, HBI – Harvey Bradshaw Index, SCCAI – Simple Clinical Colitis Activity Index, PMS – Partial Mayo Score.
^† Belgium, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, the Netherlands, Poland, Portugal, Spain, Sweden and the United Kingdom.
^‡The studies are rated as having a high risk of bias, some concerns or low risk of bias.

Conclusion

In this systematic review and meta-analysis, we find that SARS-CoV-2 infection does not increase the risk of long-term adverse IBD-related outcomes. High-quality studies with longer follow-up periods are required to understand the long-term impact of SARS-CoV-2 infection on IBD outcomes.

References

1. Khan RR, Lawson AD, Minnich LL, Martin K, Nasir A, Emmett MK, et al. Gastrointestinal Norovirus Infection Associated With Exacerbation of Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr. 2009 Mar;48(3):328.
2. Ozdemir B, Atay A, Kayhan MA, Ozin YO, Gokce DT, Altunsoy A, et al. Tissue quantitative RT–PCR test for diagnostic significance of cytomegalovirus infection in patients with inflammatory bowel disease and treatment response: Cytomegalovirus infection in patients with inflammatory bowel disease. Medicine (Baltimore). 2023 Aug 4;102(31):e34463.
3. Dimitroulia E, Pitiriga VC, Piperaki ET, Spanakis NE, Tsakris A. Inflammatory Bowel Disease Exacerbation Associated With Epstein-Barr Virus Infection. Dis Colon Rectum. 2013 Mar;56(3):322.
4. Zollner A, Koch R, Jukic A, Pfister A, Meyer M, Rossler A, et al. Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases. Gastroenterology. 2022;163(2):495–506.

Disclosure

Professor Charlie Lees has acted as a speaker and/or consultant to AbbVie, Janssen, Takeda, Pfizer, Galapagos, GSK, Gilead, Vifor Pharma, Ferring, Dr Falk, BMS, Boehringer Ingelheim, Novartis, Sandoz, Celltrion, Cellgene, Amgen, Samsung Bioepis, Fresenius Kabi, Tillotts, Trellus Health and Iterative Health.

Introduction

Histologic activity has emerged as an aspirational therapeutic goal in IBD management. It is not yet a formal treatment-target in either CD or UC. However, it could be used as an adjunct to mucosal healing to represent a deeper level of healing. Recent studies show that histologic healing is associated with decreased risk of clinical relapse, medication escalation and corticosteroid use, both in ulcerative colitis and Crohn's disease [1,2]. We investigated histologic remission (HR) rates and potential predictors of achieving histologic remission in an IBD cohort.

Aims & Methods

We conducted a retrospective subgroup analysis of data collected from IBD patients enrolled in an ongoing prospective cohort study. Clinical, biological, endoscopic data (including the Mayo endoscopic subscore and SES-CD score) and histopathology results were available at multiple time-points for the enrolled patients (annual visits). Mucosal healing was defined as SES-CD <3 or Mayo endoscopic score=0[3]. Histologic healing was defined as microscopic normalization of mucosal biopsies.

Results

219 patients (88 CD, 131 UC) were enrolled in our study and were prospectively followed for a median length of 2 years (range 0-5 years), totaling 452 study visits. Mucosal healing was recorded for 51 (27 UC, 24 CD, 23,2%) patients at 76(16%) different study visits. Overall, only 35(15%) patients achieved histologic healing. In the mucosal healing subgroup, histologic remission was achieved in 30(58%) patients. After logistic regression analysis, none of the investigated factors was associated with histologic remission.

Conclusion

Mucosal healing and endoscopic remission rates are low in real-life settings. Frequently used patient and disease related factors, including mucosal healing are not reliable predictors for histologic remission.

References

[1] Christensen B, Erlich J, Gibson PR, Turner JR, Hart J, Rubin DT. Histologic Healing Is More Strongly Associated with Clinical Outcomes in Ileal Crohn's Disease than Endoscopic Healing. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2518-2525.e1. doi: 10.1016/j.cgh.2019.11.056. Epub 2019 Dec 5.
[2]Battat R, Duijvestein M, Guizzetti L, Choudhary D, Boland BS, Dulai PS, Parker CE, Nguyen TM, Singh S, Vande Casteele N, Pai RK, Feagan BG, Sandborn WJ, Jairath V. Histologic Healing Rates of Medical Therapies for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Am J Gastroenterol. 2019 May;114(5):733-745. doi: 10.14309/ajg.0000000000000111.
[3] Turner D, Ricciuto A, Lewis A, D'Amico F, Dhaliwal J, Griffiths AM, Bettenworth D, Sandborn WJ, Sands BE, Reinisch W, Schölmerich J, Bemelman W, Danese S, Mary JY, Rubin D, Colombel JF, Peyrin-Biroulet L, Dotan I, Abreu MT, Dignass A; International Organization for the Study of IBD. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021 Apr;160(5):1570-1583. doi: 10.1053/j.gastro.2020.12.031. Epub 2021 Feb 19. PMID: 33359090.

Introduction

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and endometriosis are two nosological frameworks affecting young women. They share a spectrum of abdominal symptoms and partially common pathophysiological mechanisms involving immune system dysregulation. It is described that women with endometriosis have a higher risk of developing IBD. However, the impact of endometriosis on IBD is poorly understood. The aim of our study was to evaluate the impact of the coexistence of both diseases on the phenotype and evolution of IBD.

Aims & Methods

We conducted a retrospective cohort study in 18 GETAID (Groupe d’Étude Thérapeutique des Affections Inflammatoires du tube Digestif) centers between June 2022 and March 2023. Any patient with both endometriosis and IBD was eligible for inclusion. They were then randomly matched to 1 or 2 patients with IBD without endometriosis, according to the following criteria: type of IBD (CD or UC), year of birth (± 5 years), year of IBD diagnosis (± 4 years), and date of the last consultation (± 2 years). Data from non-exposed patients (IBD alone) were collected from a single center (CHU de Lille). The evolution of IBD was assessed using a composite severity criterion including intestinal damage (stenosis, fistula, or intra-abdominal abscess) or the need for intestinal resection surgery. The use of immunosuppressants and biologics was also recorded.

Results

In total, 207 patients with both endometriosis and IBD (149 CD and 58 UC) were included and matched to 409 patients with IBD alone. The median age of patients at the diagnosis of IBD was 23 years [IQR 18; 29]. The median follow-up duration for IBD was 10 years [5.75; 17]. For patients with CD, there was no difference between the two groups regarding disease location, disease phenotype, and anoperineal involvement. For patients with UC, there was a difference in disease extent with more rectal involvement in the endometriosis group (29.3% vs 12.6%; p=0.03). Patients exposed to endometriosis had significantly less use of immunosuppressive treatments (UC p < 0.01; CD p < 0.001) and biologics (UC p < 0.01; CD p < 0.001), both anti-TNF (UC p=0.01; CD p < 0.001) and non-anti-TNF (UC p=0.04; CD p=0.001). In the actuarial analysis according to the composite severity criterion, patients exposed to endometriosis had a more favorable evolution of their CD than non-exposed patients (HR=0.68; 95% CI [0.50; 0.92]; p=0.011). In the subgroup of patients with CD who underwent surgery for their endometriosis during follow-up (n=72), a less severe progression was also observed (HR=0.65; 95% CI [9.42; 1]; p=0.05). The luminal surgery rate for CD in these patients was lower (32.2% vs 43.9%; p=0.01) in the "exposed" group. No difference was observed for anoperineal manifestations (p=0.16) and the use of anoperineal surgery (p=0.82). For the UC group, those with endometriosis seemed to have a less favorable disease course, according to the composite severity criterion (HR=1.73; 95% CI [0.74; 4.00]; p=0.20). However, the rate of colectomy was not significantly higher for exposed patients (19.0% vs 11.5%; p=0.20).

Conclusion

Although patients with endometriosis are at a higher risk of developing IBD, it does not negatively influence the course of IBD. On the contrary, patients with CD appear to have a less severe progression, with significantly less exposure to immunosuppressants and biologics. However, both conditions have a major impact on patients, requiring multidisciplinary follow-up to ensure symptom control and improve their quality of life.

Introduction

Inflammatory Bowel Disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition affecting the gastrointestinal tract. Although primarily associated with intestinal symptoms, IBD has also been linked to various extraintestinal complications, including liver fibrosis (LF). Additionally, metabolic-associated steatotic liver disease (MASLD), a common liver condition driven by metabolic risk factors such as obesity and insulin resistance, could intersect with IBD, given its systemic nature.
While both LF and MASLD are prevalent among the general population, their incidence and associated risk factors in IBD patients remain underexplored. Understanding these liver-related complications is crucial for developing effective screening and management strategies for patients with IBD.

Aims & Methods

We aimed to assess the prevalence of LF and MASLD in IBD patients compared to matched controls. In this cross-sectional, case-control study, we enrolled consecutive IBD patients from an IBD referral center and matched controls from the general population based on age, sex, type 2 diabetes (T2D) status, and body mass index (BMI) in a 1:1 ratio. Liver fibrosis and MASLD were confirmed through shear-wave elastography (SWE) measurements of stiffness and attenuation coefficient. Potential risk factors were analyzed using multivariate logistic regression.

Results

We included 378 participants, comprising 200 IBD patients (106 with CD and 94 with UC) and 178 controls. There were no statistically significant differences regarding distribution by gender, age, T2D status and BMI. The prevalence of LF (SWE ≥ 6.78 kPa) and advanced LF (SWE ≥ 9.15 kPa) was 42.5% and 16.0%, respectively, in IBD patients (48.1% in CD vs. 36.2% in UC; p=0.088) and 28.1% and 9.0%, respectively, in the control group (p<0.05). For UC, history of complicated disease (OR 7.5, CI95% 1.2-46.2 p<0.05) and multiple hospitalizations due to acute disease (OR 5.6, CI95% 1.3-24.8; p<0.05) were significant risk factors. As for CD, previous hospitalizations (OR 9.7, CI95% 1.4-65.8; p<0.05) and heavy smoking habits (OR 4.9, CI95% 2.0-12.4; p<0.001) were the main risk factors. Extraintestinal manifestations, higher fecal calprotectin level at the time of liver stiffness measurement and latest endoscopic activity were not associated with presence of LF. MASLD was not significantly different between IBD and control group (42.0% vs. 51.7%, respectively; p>0.05). Higher BMI, higher waist circumference, higher abdominal wall thickness and metabolic syndrome were significant risk factors for MASLD (p<0.001).

Conclusion

Our case-control study demonstrates that patients with IBD have a higher prevalence of liver fibrosis compared to matched controls, with significant risk factors including a history of complicated disease, multiple hospitalizations, and heavy smoking habits. Conversely, the prevalence of MASLD does not significantly differ between IBD patients and controls, suggesting that metabolic factors might play a more substantial role in MASLD risk. Given these findings, it is critical for clinicians to implement routine liver fibrosis surveillance in IBD patients, especially in those with identified risk factors. Proactive management strategies aimed at reducing risk factors, such as smoking cessation and minimizing hospitalizations through effective disease management, could mitigate liver fibrosis risk in this population. These insights emphasize the need for integrated care approaches that address both IBD-related complications and associated liver health.