Mucosal Healing and Clinical Efficacy of Adalimumab in Small Intestinal Crohn's Disease (SIMCHA Study): Final Results From a Prospective, Open-Label, Single-Arm Study.

BACKGROUND: Endoscopic healing is a key treatment target in inflammatory bowel disease; few data are available on the clinical and endoscopic efficacy of biological therapy in upper gastrointestinal Crohn's disease. This study aimed to investigate small bowel mucosal healing and clinical efficacy of adalimumab therapy by video capsule endoscopy in patients with endoscopically active upper gastrointestinal Crohn's disease. METHODS: This prospective, open-label, single-arm study included Crohn's disease patients with moderate-severe endoscopic proximal small bowel involvement, defined by a Lewis score >790. Patients were treated with adalimumab monotherapy for 24 weeks. Co-primary outcomes were endoscopic healing, defined as Lewis score <350, and endoscopic response, defined as >50% decrease in Lewis score. Secondary outcomes included clinical (Harvey-Bradshaw index <4) and biomarker remission (fecal calprotectin <250 µg/g, and C-reactive protein <5 mg/L). RESULTS: A total of 59 Crohn's disease patients were screened; 17 patients have met eligibility criteria and were enrolled. Endoscopic healing was observed in 8 patients (47.1%) and endoscopic response in additional 5 patients (29.4%) at 24 weeks. Median Lewis score was significantly decreased compared to baseline (1912 vs. 337, P = .0005). Eleven of 13 patients (84.6%) with clinical activity achieved clinical remission (baseline: 13/17 vs. week 24: 2/17, P < .0001). Nine of 10 patients with elevated C-reactive protein achieved normal C-reactive protein after treatment and the median C-reactive protein significantly decreased from 7.4 to 1.6 mg/L, P = .032. In contrast, no change was observed in fecal calprotectin pre- and posttreatment. CONCLUSIONS: Adalimumab induced endoscopic healing and clinical remission in patients with active small bowel Crohn's disease, with approximately half of the patients achieving endoscopic healing.

Adherence to Objective Therapeutic Monitoring and Outcomes in Patients with Inflammatory Bowel Disease with Adalimumab Treatment. A Real-world Prospective Study.

BACKGROUND AND AIMS: Objective monitoring and effective early treatment using a treat-to-target approach are key to improving therapeutic outcomes in IBD patients. This study aimed to assess adherence to objective monitoring (clinical, biomarkers, and endoscopy) and its impact on clinical outcomes. METHODS: A prospective, multicenter study included consecutive IBD patients starting on adalimumab therapy between January 2019 and December 2020. Disease activity, assessed by the Harvey-Bradshaw index (HBI), partial Mayo, C-reactive protein (CRP), fecal calprotectin (FCAL), and endoscopy were evaluated at adalimumab initiation and 3, 6, 9 and 12 months. Therapeutic drug monitoring, changes in treatment, drug sustainability, and clinical outcomes were assessed. RESULTS: 104 IBD patients were enrolled (78.8% CD, median age 34.3 years, disease duration 9 years). During the 12 months follow-up, high adherence to clinical activity assessment was observed in both CD (81.3%- 87.7%) and UC patients (76.5-90.9%). CRP measurement decreased over time in both CD (37.3%-54.9%) and UC (29.4%-50.0%). The adherence to serial FCAL monitoring was low in CD (22.7-31.3%) and UC patients (17.6-56.0%). UC patients had higher adherence to early endoscopic assessment (<6 months) compared to CD patients (40.9% vs. 21.5%). Adherence to early combined clinical and biomarkers resulted in earlier dose optimization in CD and UC (log-rank<0.001), but drug sustainability was not different. The patients with early combined adherence had a significantly higher clinical remission rate at 1 year compared to non-adherence (70.2% vs. 29.8%, p=0.007) but no significant difference in UC patients. CONCLUSIONS: The adherence to early objective monitoring with combined clinical and biomarkers assessment in IBD patients starting adalimumab therapy led to dose optimization and improved 1-year clinical remission in CD but did not change drug sustainability and clinical remission in UC.

Effectiveness, safety, and drug sustainability of biologics in elderly patients with inflammatory bowel disease: A retrospective study.

BACKGROUND: Biologic therapy resulted in a significant positive impact on the management of inflammatory bowel disease (IBD) however data on the efficacy and side effects of these therapies in the elderly is scant. AIM: To evaluate retrospectively the drug sustainability, effectiveness, and safety of the biologic therapies in the elderly IBD population. METHODS: Consecutive elderly (≥ 60 years old) IBD patients, treated with biologics [infliximab (IFX), adalimumab (ADAL), vedolizumab (VDZ), ustekinumab (UST)] followed at the McGill University Inflammatory Bowel Diseases Center were included between January 2000 and 2020. Efficacy was measured by clinical scores at 3, 6-9 and 12-18 mo after initiation of the biologic therapy. Patients completing induction therapy were included. Adverse events (AEs) or serious AE were collected during and within three months of stopping of the biologic therapy. RESULTS: We identified a total of 147 elderly patients with IBD treated with biologicals during the study period, including 109 with Crohn's disease and 38 with ulcerative colitis. Patients received the following biologicals: IFX (28.5%), ADAL (38.7%), VDZ (15.6%), UST (17%). The mean duration of biologic treatment was 157.5 (SD = 148) wk. Parallel steroid therapy was given in 34% at baseline, 19% at 3 mo, 16.3% at 6-9 mo and 6.5% at 12-18 mo. The remission rates at 3, 6-9 and 12-18 mo were not significantly different among biological therapies. Kaplan-Meyer analysis did not show statistical difference for drug sustainability (P = 0.195), time to adverse event (P = 0.158) or infection rates (P = 0.973) between the four biologics studied. The most common AEs that led to drug discontinuation were loss of response, infusion/injection reaction and infection. CONCLUSION: Current biologics were not different regarding drug sustainability, effectiveness, and safety in the elderly IBD population. Therefore, we are not able to suggest a preferred sequencing order among biologicals.

Safety of Biological Therapies in Elderly Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.

Background and Aim: Newer biologics appeared safer in landmark clinical trials, but their safety is understudied in vulnerable populations. The aim of the present study was to perform a systematic review and meta-analysis to assess the safety of available biologicals in the elderly IBD population. Methods: We systematically searched PubMed/Medline and conference proceedings between 1 April 1969 and 1 June 2021 to identify eligible studies that examined the safety of biologics in elderly patients with IBD. Of the 2885 articles and 12 congress abstracts identified, 12 peer reviewed papers and 3 abstracts were included after independent evaluation by two reviewers. The identified studies collected safety data on anti-TNF, vedolizumab (VDZ) and ustekinumab (UST). Results: Rates of AE and infections were not different among the biologics (AE mean rate: 11.3 (CI 95% 9.9-12.7)/100 pts-years; p = 0.11, infection mean rate: 9.5 (CI 95% 8.4-10.6)/100 pts-years; p = 0.56) in elderly IBD patients on anti-TNF, VDZ or UST. Infusion/injection reaction rates were more common on anti-TNFs (mean rate: 2.51 (CI 95% 1.7-3.4/100 pts-years; p = 0.02). and malignancy rates were higher on VDZ/UST (mean rate: 2.14 (CI 95% 1.6-2.8)/100 pts-years; p = 0.01). Conclusions: Rates of AEs and infections were not different among biologicals. Infusion/injection reactions were more common on anti-TNFs. Current data are insufficient to suggest the sequencing of biologicals in elderly patients based on safety.

The Optimal Management of Fistulizing Crohn's Disease: Evidence beyond Randomized Clinical Trials.

Fistulizing Crohn's disease (FCD) remains the most challenging aspect of treating patients with CD. FCD can occur in up to 30% of patients with CD and may lead to significant disability and impaired quality of life. The optimal treatment strategies for FCD require a multidisciplinary approach, including a combined medical and surgical approach. The therapeutic options for FCD are limited due to sparse evidence from randomized clinical trials (RCTs). The current recommendations are mainly based on post hoc analysis from RCTs, real-world clinical studies and expert opinion. There is variation in everyday clinical practice amongst gastroenterologists and surgeons. The evidence for anti-tumor necrosis factor therapy is the strongest in the treatment of FCD. However, long-term fistula healing can be achieved in only 30-50% of patients. In recent years, emerging data in the advent of therapeutic modalities, including the use of new biologic agents, therapeutic drug monitoring, novel surgical methods and mesenchymal stem cell therapy, have been shown to improve outcomes in achieving fistula healing. This review summarizes the existing literature on current and emerging therapies to provide guidance beyond RCTs in managing FCD.

Hereditary Nonpolyposis Colorectal Cancer in Association with Crohn's Disease and Lynch Syndrome: The Importance of a Strict Endoscopic Surveillance.

Crohn's disease (CD) and Lynch syndrome (LS) are two different entities, yet both are associated with increased risk of colorectal cancer (CRC). We present the case of a young female patient in long-standing remission of her ileocolonic luminal CD, and a family history of LS on a regular short interval (every 2 years) colonoscopy surveillance. Despite normal blood tests, fecal calprotectin, and ileocolonoscopy, her last colonoscopy showed an approximately 1.3-1.5 cm polyp in the cecum and mild UC-like colitis in the ascending colon. Histology confirmed the presence of a moderately differentiated adenocarcinoma (T2N0M0) with loss of PSM2 expression at immunohistochemistry, in line with a hereditary nonpolypoid CRC associated origin. Laparoscopic subtotal colectomy with ileorectal anastomosis was offered as the treatment of choice, which revealed a 2.4 cm exophytic ulcerated lesion and pathology confirmed invasive moderately differentiated adenocarcinoma (pT2N0M0). Patient will remain on close endoscopic surveillance for the rectum. Our case highlights the importance of a strict endoscopic surveillance in patients with long-standing CD colitis, especially in patients with additional risk factors. The aim of this article was to highlight the importance of a strict endoscopic surveillance in CD in association with LS regarding a higher risk of CRC, which mandates the adaptation of the endoscopic surveillance intervals as well as the surgical approach and postoperative management/surveillance.

Is There a Best First Line Biological/Small Molecule in IBD: Are We Ready for Sequencing?

Inflammatory bowel disease (IBD) is a chronic, life-long inflammatory condition of the gastrointestinal tract. Treatment strategy depends on the severity of the disease course. IBD physicians need to be aware of the life-long treatment options available. The goal is not only to achieve clinical remission but to halt or stabilize the chronic inflammation in the intestines to prevent further structural damage. Therefore, the use of early biologic therapy is recommended in moderate-to-severe IBD patients. However, in the last decade, use of therapeutic drug monitoring has increased considerably, opening an opportunity for sequencing. This review summarizes the available evidence on biologic and small molecules therapy in Crohn's disease (CD) and ulcerative colitis (UC) in different clinical scenarios, including perianal CD, the elderly, extra intestinal manifestations, and pregnancy.

Increased Prevalence of Myocardial Infarction and Stable Stroke Proportions in Patients with Inflammatory Bowel Diseases in Quebec in 1996-2015.

BACKGROUND: Chronic inflammatory diseases are linked to an increased risk of atherothrombotic events, but the risk associated with inflammatory bowel disease (IBD) is controversial. We therefore examined the risk of and risk factors for myocardial infarction (MI) and stroke in IBD patients. METHODS: We used the public health administrative database from the Province of Quebec, Canada, to identify IBD patients newly diagnosed between 1996 and 2015. The incidence and prevalence of MI and stroke in IBD patients were compared to those for the Canadian population. RESULTS: A cohort of 35,985 IBD patients was identified. The prevalence but not incidence rates of MI were higher in IBD patients (prevalence: 3.98%; incidence: 0.234) compared to the Canadian rates (prevalence: 2.0%; incidence: 0.220), while the prevalence and incidence rates of stroke were not significantly higher in the IBD patients (prevalence: 2.98%; incidence: 0.122, vs. Canadian rates: prevalence: 2.60%; incidence: 0.297). We identified age, female gender, hyperlipidemia, diabetes, and hypertension (p < 0.001 for each) as significant risk factors associated with MI and stroke in IBD. Exposure to biologics was associated with a higher incidence of MI (IRR: 1.51; 95% CI: 0.82-2.76; p = 0.07) in the insured IBD population. CONCLUSIONS: An increased prevalence but not incidence of MI and no increased risk of stroke were identified in this population-based IBD cohort.

Clinical Outcomes of COVID-19 and Impact on Disease Course in Patients with Inflammatory Bowel Disease.

Background and Aims: The impact of COVID-19 has been of great concern in patients with inflammatory bowel disease (IBD) worldwide, including an increased risk of severe outcomes and/or possible flare of IBD. This study aims to evaluate prevalence, outcomes, the impact of COVID-19 in patients with IBD, and risk factors associated with severe COVID-19 or flare of IBD activity. Methods: A consecutive cohort of IBD patients who were diagnosed with COVID-19 infection and followed up at the McGill University Health Care Centre was obtained between March 1, 2020, and April 30, 2021. Demographics, comorbidities, IBD (type, treatments, pre- and post-COVID-19 clinical activity, biomarkers, and endoscopic activity), and COVID-19-related outcomes (pneumonia, hospitalization, death, and flare of IBD disease) were analyzed. Results: A cohort of 3,516 IBD patients was included. 82 patients (2.3%) were diagnosed with COVID-19 infection (median age: 39.0 (IQR 27.8-48.0), 77% with Crohn's disease, 50% were female). The prevalence of COVID-19 infection in IBD patients was significantly lower compared to the general population in Canada and Quebec (3.5% versus 4.3%, p < 0.001). Severe COVID-19 occurred in 6 patients (7.3%); 2 patients (2.4%) died. A flare of IBD post-COVID-19 infection was reported in 8 patients (9.8%) within 3 months. Biologic therapy was held during active COVID-19 infection in 37% of patients. Age ≥55 years (odds ratio (OR): 11.1, 95% CI: 1.8-68.0), systemic corticosteroid use (OR: 4.6, 95% CI: 0.7-30.1), active IBD (OR: 3.8, 95% CI: 0.7-20.8), and comorbidity (OR: 4.9, 95% CI: 0.8-28.6) were factors associated with severe COVID-19. After initial infection, 61% of IBD patients received COVID-19 vaccinations. Conclusion: The prevalence of COVID-19 infection among patients with IBD was lower than that in the general population in Canada. Severe COVID-19, mortality, and flare of IBD were relatively rare, while a large proportion of patients received COVID-19 vaccination. Older age, comorbidities, active IBD disease, and systemic corticosteroid, but not immunosuppressive or biological therapy, were associated with severe COVID-19 infection.

Treatment Targets in Ulcerative Colitis: Is It Time for All In, including Histology?

The main therapeutic goal of ulcerative colitis (UC) is to induce and maintain remission to prevent long-term disease progression. Treat-to-target strategies, first introduced by the STRIDE consensus and updated in 2021, have shifted focus from symptomatic control toward more stringent objective endpoints. Today, patient monitoring should be based on a combination of biomarkers and clinical scores, while patient-reported outcomes could be used as short-term targets in monitoring disease activity and therapeutic response. In addition, endoscopic healing was the preferred long-term goal in UC. A Mayo endoscopic score (MES) ≤ 1 can be recommended as a minimum target. However, recent evidence suggests that more stringent endoscopic goals (MES of 0) are associated with superior outcomes. Recently, emerging data support that histological remission (HR) is a superior prognostic factor to endoscopic healing in predicting long-term remission. Despite not yet being recommended as a target, HR may become an important potential therapeutic goal in UC. However, it remains questionable if histological healing should be used as a routine assessment in addition to clinical, biomarker, and endoscopic targets in all patients. Therefore, in this review, our aim was to discuss the current evidence for the different treatment targets and their value in everyday clinical practice.

A prospective randomized trial of intralesional triamcinolone injections after endoscopic dilation for complex esophagogastric anastomotic strictures: steroid injection after endoscopic dilation.

BACKGROUND AND AIMS: Postoperative esophageal strictures frequently recur. We assessed the efficacy of injecting triamcinolone after bougie dilation in comparison to dilation alone. METHODS: In a double-blind randomized fashion, 19 patients (68% male with mean age of 53-years old) with non-dilated esophagogastric complex strictures after esophagectomy with gastric pull-up were assigned to receive dilation alone (control) or 40 mg of triamcinolone at the borders of the wall lacerations caused by the bougienage in each dilation session during the study follow-up. Dysphagia and complications were assessed at 1, 2, and 6 months. Primary end-point was to be dysphagia-free. RESULTS: After 1 month of the beginning of therapy, 4 patients in the steroid group were without dysphagia, in comparison to 0 patient in the control group (P = 0.021). Six months after endoscopic therapy, 62% of the cases in the triamcinolone group versus none in the control group were dysphagia-free (P = 0.009). There was no perforation nor hemorrhage. CONCLUSIONS: Injecting triamcinolone after every dilation session next to or at the borders of the lacerations caused by the dilators, results in a significant improvement or resolution of dysphagia.