Exabis Library

Educational objectives:
1. To understand the growing prevalence of IBD in older people.
2. To understand the specific challenges in older patients relating to co-morbidities, polypharmacy and the limited data to guide care.
3. To understand the vulnerability of older patients to the effects of corticosteroids.
4. To discuss immunomodulators, biologics (and surgery) as options in the older IBD patient.
5. To consider carefully an individual's risk of infection, malignancy and their overall fitness in decision-making.

Mads Wewer reports on the analysis of population data from Denmark tracking the incidence and complications of peri-anal Crohn’s disease.

Perianal Crohn's disease (pCD) may present with a variety of lesions that include anal skin tags, anal canal lesions including fissures, ulcers, fistula and abscesses, strictures and cancer. pCD is disabling and aggressive phenotype that negatively impacts on the quality of life of affected patients. Perianal fistulas are common manifestations of pCD, with an incidence of 11 cases per 1000 patient-years. Successful treatment of pCD remains still a struggle for both physicians and patients. Significant advances in the management of pCD have occurred in the last two decades, resulting in the concept of a collaborative multidisciplinary approach using the latest medical therapies combined with modern surgical or endoscopic techniques. The use of antibiotics in the treatmentof pCD has limited evidence and antibiotics are currently used in combination with other therapies to prevent abscess formation and improve the rate of fistula closure. Thiopurines in pCD lacks of prospective trials, and evidence supporting their use should be carefully interpreted. Although anti-TNFs have revolutionized the prognosis for patients with pCD in the modern era, their effectiveness in the long term is limited: over 60% may relapse after one year of treatment and less than one third mantain sustained remission over time. Optimisation of anti-TNF treatment in pCD includes associaton with an antibiotic for the induction of fistula remission, combination with thiopurines to achieve appropriate anti-TNF trough level and a low likelihood of anti-drug antibodies. The use of vedolizumab and ustekinumab in pCD after anti-TNFs failure is mainly supported by one randomized phase IV trial (vedolizumab) and a number of real life reports (vedolizumab and ustekinumab), suggesting that they could be beneficial in patients who have failed to respond to anti-TNFs. Finally, in case of refractory pCD, a number of mesenchymal stem cell (MSC)-based therapies have been reported. In particular the use of darvadstrocel in refractory pCD is supported by phase 3 trial, showing that local treatment with adult allogeneic expanded adipose tissue-derived mesenchymal stem cells may succeed in 50% of treated patients after 6 months.

Learning Objectives:
1. Aspects of risk stratification
2. Utility of drugs that may alter the natural history (reducing rates of surgeries and complications)
3. Timing of intervention
4. Evidence base data  comparing different classes
5. Economic consideration/medical economics including the utility of biosimilars

Several potential risk factors for disease recurrence after surgery have been identified, includingage, disease phenotype, and smoking. In the light of the evolution of prevention and management ofpostoperative recurrence, including early immunosuppressive and biologic treatments, theidentification of potential risk factors is pivotal. Despite the clinical significance, few studies haveinvestigated the association between postoperative complications and recurrence in Crohn’s disease(CD) patients after primary ileocolonic resection. A retrospective analysis of consecutive patientsundergoing primary ileocolonic resection for CD at two European referral centers was performed toaddress the effect of postoperative complications on endoscopic and clinical recurrence. Data from262 patients were retrieved from the Institutional databases: 145 patients developed endoscopicrecurrence and 117 patients were recurrence-free. At multivariable analysis, smoking, penetratingphenotype, perianal disease, and postoperative complications were risk factors for endoscopicrecurrence. Postoperative complications and penetrating disease significantly reduce the time toendoscopic recurrence; postoperative complications and penetrating disease significantly shortenthe time to clinical recurrence. In summary, postoperative complications rate was an independentrisk factor for endoscopic recurrence after primary surgery for CD and affected the rate and timingof endoscopic and clinical disease recurrence.

Crohn’s disease is a chronic progressive inflammatory disease of the gastro-intestinal tract that may lead to bowel damage and disability. Half of patients will require surgery within ten years of diagnosis. Unfortunately, surgery is not curative, endoscopic recurrence is reported in 80% of patients within one year of diagnosis, and predicts clinical and surgical recurrence. The prevention of post-surgical recurrence is a critical target in the care of Crohn’s disease after surgery. Currently, postsurgical management and treatment of Crohn’s disease are based on endoscopic monitoring performed during the first year after surgery. However, colonoscopy is an invasive and expensive procedure, unpleasant to patients. Bowel ultrasound is a cheap, non-invasive, readily-available tool for the assessment and the monitoring of patients with inflammatory bowel disease, especially patients with Crohn’s disease. This presentation aims to review the evidence for the use of bowel ultrasound in the specific setting of postsurgical recurrence in Crohn’s disease; the diagnostic accuracy of bowel ultrasound in the detection of postsurgical recurrence in alternative to colonoscopy; its predictive value for clinical and surgical recurrence.

Jérémie Lefevre discusses the work of the GETAID surgical group examining post-operative outcomes for a large series of patients undergoing repeat ileocolonic resection and reports some reassuring findings.

The current novel coronavirus (SARS-CoV-2) pandemic is an ongoing global health crisis, which represents an important challenge for the whole society and mankind. Patients with inflammatory bowel disease (IBD) are treated with immunosuppressive drugs that are usually associated with more severe viral infections. However, the effects of the different therapies on the risk of SARS-CoV-2 infection and Covid-19 severity in IBD patients are still under investigation.

Between April 2020 and April 2021, 238 IBD patients (N=145 with Crohn disease and N=93 with Ulcerative colitis) of the North Italy area have been enrolled. Both serum samples (N=238 IBD patients and N=45 healthy donors) and colon biopsies from inflamed and non-inflamed mucosa (N=88 IBD patients N=20 non-IBD control) have been collected. To evaluate the exposure to SARS-CoV-2, both clinical data and seroprevalence of anti-SARS-CoV-2 Ab have been analyzed. Serum samples were analyzed by untargeted metabolomics analysis and the frequency of a serum metabolomics signature associated with protection were evaluated in IBD versus healthy donors. Moreover, gene expression analysis of key proteins for virus entry (ACE2, TMPRSS2, TMPRSS4, ADAM17) were analyzed by qPCR in the gut mucosa biopsies of IBD patients.

The seroprevalence of anti-SARS-CoV-2 Ab in our cohort of IBD patients (10/238) indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy. Accordingly, we observed that the serum metabolomics signature associated with protection was more frequent in IBD patients treated with anti-TNF (N=50, 70%), than healthy controls (N=45, 50%). Gene expression analysis of the proteins involved in SARS-CoV-2 entry also indicated that IBD patients treated with anti-TNF (N=14) had a lower mucosal level of SARS-CoV-2 receptor ACE2 and its sheddase ADAM17 than non-IBD subjects along with higher expression of the proteases TMPRSS2 and TMPRSS4.  Moreover, vedolizumab-treated patients (N=7) showed a significant lower expression of ACE2, TMPRSS2 and TMPRSS4 than controls, whereas ADAM17 levels were similar.

Our study indicates that IBD population treated with biologics has an overall lower risk to contract SARS-CoV-2 infection. Future studies to gather the mechanisms underpinning the effects of biologics on the expression of the proteins involved in SARS-CoV-2 viral entry in association with the specific metabolomics signature of viral susceptibility might shed light on potential targets to increase resistance in higher risk subgroups of patients.

The ileal pouch-anal anastomosis (IPAA) is the gold standard to restore intestinal continuity inpatients with ulcerative colitis (UC), familial adenomatous polyposis (FAP), and in selected patientswith Crohn’s disease (CD) undergoing proctocolectomy. IPAA produces reasonable long termresults and is associated with low mortality as well as good patient satisfaction. However, long-term pouch failure may occurs in a minority of cases. Various IPAA-related complications such asanastomotic leakage, pelvic sepsis, fistula, stricture, pouchitis and “crouchitis” are associatedwith pouch failure. Pelvic sepsis is reported to be the most important risk factor for pouch failure.The rate of IPAA-related complications varies widely in the literature and may have increased inthe era of biologics. However, ambiguous definitions for anastomotic complications, differences inpostoperative assessment, and duration of follow-up make a comparison of outcomes followingIPAA challenging. Although re-do pouch surgery is feasible it has been generally associated withworse outcome when compared to primary surgery. For this reason pouch surgery has the right tobe considered as a “once in a life time surgery”. To reduce the risk of pelvic sepsis, the focus hasbeen on optimization of preoperative performance status, staged procedures, fecal diversion, andadequate postoperative management (ie, early detection and pro-active treatment of anastomoticleaks). From a technical point of view, since its introduction in 1978, restorative proctocolectomyhas gone through a progressive evolution including the application of stapled anastomosis,minimally invasive approach and transanal technique. Transanal techniques and single stapledanastomosis have the potential to standardize the length and shape of the rectal cuff and thereliability of the anastomosis respectively with subsequent impact of long term outcomes in termsof function.