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.

Diarrhea-Predominant Irritable Bowel Syndrome: Medical Management Update.

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder, which impacts the quality of life, work productivity and social activities of patients. Diarrhea-predominant IBS (IBS-D) is one of several subtypes, and accounts for approximately one third of all cases. Currently available treatments are typically unable to alleviate the cardinal symptoms of IBS-D, including abdominal pain and diarrhea, and a clinical unmet need remains for an effective treatment which simultaneously relieves multiple symptoms. Patients may benefit from a multipronged, individualized approach, including dietary modifications, and psychological and pharmacological therapies. The aim of this review is to provide an update on the available and upcoming treatment options for IBS-D in Canada, with reference to the recently updated Canadian IBS consensus guidelines. Initial treatment approaches include lifestyle modifications, dietary modifications, and non-prescription therapies such as peppermint oil. While some medications such as tricyclic antidepressants are also used to treat IBS-D symptoms, eluxadoline and rifaximin are the only two pharmacological therapies approved for the treatment of IBS-D in Canada. Key clinical trial data for the currently available pharmacological options are presented to provide an overview of the efficacy and safety of these agents.

Ulcerative Colitis Remission Status After Induction With Mesalazine Predicts Maintenance Outcomes: the MOMENTUM Trial.

BACKGROUND AND AIMS: This study assessed the efficacy of maintenance treatment with multimatrix mesalazine following achievement of complete or partial remission after induction treatment with high-dose multimatrix mesalazine. METHODS: In this phase 3b/4, open-label, multicentre, prospective, single-arm study, patients with mild-to-moderate ulcerative colitis were treated with multimatrix mesalazine 4.8g/day once daily for 8 weeks [induction phase]. At Week 8, those who achieved complete or partial remission, based on predefined clinical and endoscopic criteria, were eligible to receive 12 months of multimatrix mesalazine 2.4g/day once daily maintenance therapy. The primary endpoint was the proportion of patients in complete remission at Month 12. RESULTS: A total of 717 patients received induction treatment; 25.9% and 39.3% of patients achieved complete and partial remission, respectively, at Week 8. A total of 461 patients entered the maintenance phase. The likelihood of remaining in/achieving complete remission at Month 12 was higher for patients who entered the maintenance phase in complete remission compared with those who began maintenance in partial remission [47.8% vs 26.0%; p < 0.001]. At Month 12, mucosal healing [endoscopy score ≤ 1] was demonstrated in 76.4% [139/182] and 63.5% [176/277] of those who were in complete and partial remission, respectively, at the end of induction. CONCLUSION: Patients achieving complete remission before dose reduction were more likely to remain in remission at Month 12.

Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials.

CONTEXT: Maintenance therapy for Crohn disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority. OBJECTIVE: To determine whether the oral administration of omega-3 free fatty acids is more effective than placebo for prevention of relapse of Crohn disease. DESIGN, SETTING, AND PATIENTS: Two randomized, double-blind, placebo-controlled studies (Epanova Program in Crohn's Study 1 [EPIC-1] and EPIC-2) conducted between January 2003 and February 2007 at 98 centers in Canada, Europe, Israel, and the United States. Data from 363 and 375 patients with quiescent Crohn disease were evaluated in EPIC-1 and EPIC-2, respectively. INTERVENTIONS: Patients with a Crohn's Disease Activity Index (CDAI) score of less than 150 were randomly assigned to receive either 4 g/d of omega-3 free fatty acids or placebo for up to 58 weeks. No other treatments for Crohn disease were permitted. MAIN OUTCOME MEASURE: Clinical relapse, as defined by a CDAI score of 150 points or greater and an increase of more than 70 points from the baseline value, or initiation of treatment for active Crohn disease. RESULTS: For EPIC-1, 188 patients were assigned to receive omega-3 free fatty acids and 186 patients to receive placebo. Corresponding numbers for EPIC-2 were 189 and 190 patients, respectively. The rate of relapse at 1 year in EPIC-1 was 31.6% in patients who received omega-3 free fatty acids and 35.7% in those who received placebo (hazard ratio, 0.82; 95% confidence interval, 0.51-1.19; P = .30). Corresponding values for EPIC-2 were 47.8% and 48.8% (hazard ratio, 0.90; 95% confidence interval, 0.67-1.21; P = .48). Serious adverse events were uncommon and mostly related to Crohn disease. CONCLUSION: In these trials, treatment with omega-3 free fatty acids was not effective for the prevention of relapse in Crohn disease. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: EPIC-1: NCT00613197, EPIC-2: NCT00074542.

Evidence-based recommendations for short- and long-term management of uninvestigated dyspepsia in primary care: an update of the Canadian Dyspepsia Working Group (CanDys) clinical management tool.

The present paper is an update to and extension of the previous systematic review on the primary care management of patients with uninvestigated dyspepsia (UD). The original publication of the clinical management tool focused on the initial four- to eight-week assessment of UD. This update is based on new data from systematic reviews and clinical trials relevant to UD. There is now direct clinical evidence supporting a test-and-treat approach in patients with nondominant heartburn dyspepsia symptoms, and head-to-head comparisons show that use of a proton pump inhibitor is superior to the use of H2-receptor antagonists (H2RAs) in the initial treatment of Helicobacter pylori-negative dyspepsia patients. Cisapride is no longer available as a treatment option and evidence for other prokinetic agents is lacking. In patients with long-standing heartburn-dominant (ie, gastroesophageal reflux disease) and nonheartburn-dominant dyspepsia, a once-in-a-lifetime endoscopy is recommended. Endoscopy should also be considered in patients with new-onset dyspepsia that develops after the age of 50 years. Conventional nonsteroidal anti-inflammatory drugs, acetylsalicylic acid and cyclooxygenase-2-selective inhibitors can all cause dyspepsia. If their use cannot be discontinued, cotherapy with either a proton pump inhibitor, misoprostol or high-dose H2RAs is recommended, although the evidence is based on ulcer data and not dyspepsia data. In patients with nonheartburn-dominant dyspepsia, noninvasive testing for H pylori should be performed and treatment given if positive. When starting nonsteroidal anti-inflammatory drugs for a prolonged course, testing and treatment with H2RAs are advised if patients have a history of previous ulcers or ulcer bleeding.