Neeraj Narula

The Real-World Effectiveness and Safety of Vedolizumab for Moderate-Severe Crohn's Disease: Results From the US VICTORY Consortium.

Objectives:We assessed the real-world effectiveness and safety of vedolizumab (VDZ) in moderate–severe Crohn’s disease (CD).Methods:Retrospective cohort study of seven medical centers, from May 2014 to December 2015. Adults with moderate-severe CD treated with VDZ, with follow-up after initiation of therapy, were included. Using the multivariable Cox proportional hazard analyses, we identified independent predictors of clinical remission or mucosal healing with VDZ. Rates of serious infection (requiring antibiotics, resulting in discontinuation of VDZ, hospitalization or death) and serious adverse events (discontinuation of VDZ, hospitalization or death) were described quantitatively.Results:We included 212 patients with moderate–severe CD (median age 34 years; 40% male; 90% tumor necrosis factor (TNF)-antagonist exposed) with a median follow-up (IQR) of 39 weeks (25–53). Twelve-month cumulative rates of clinical remission, mucosal healing, and deep remission (clinical remission+mucosal healing) were 35%, 63%, and 26%, respectively. Individuals with prior TNF-antagonist exposure (hazard ratio (HR) 0.40; 95% confidence interval (CI): 0.20–0.81), smoking history (HR 0.47; 95% CI: 0.25–0.89), active perianal disease (HR 0.49; 95% CI: 0.27–0.88), and severe disease activity (HR 0.54; 95% CI: 0.31–0.95) were less likely to achieve clinical remission. Those with prior TNF-antagonist exposure (HR 0.29; 95% CI: 0.12–0.73), and severe disease activity (HR 0.54; 95% CI: 0.31–0.95) were less likely to achieve mucosal healing. During 160 patient years of follow-up (PYF) and 1,433 VDZ infusions, 5 patients developed infusion reactions (3.5 per 1,000 infusions), 21 developed serious infections (13 per 100 PYF), and 17 developed serious adverse events (10 per 100 PYF). A minority of adverse events required discontinuation of therapy (6 per 100 PYF).Conclusions:VDZ is a safe and effective treatment option for moderate–severe CD in routine practice. Clinical remission and deep remission (clinical remission and mucosal healing) can be achieved in 1/3 of individuals, and a minority of individuals require discontinuation of therapy due to adverse events.

Meta‐analysis: peri‐operative anti‐TNFα treatment and post‐operative complications in patients with inflammatory bowel disease

The impact of peri‐operative use of TNFα antagonists on post‐operative complications such as infection and wound healing is controversial.

Systematic review with meta‐analysis: mucosal healing is associated with improved long‐term outcomes in Crohn's disease

Clinical manifestations of Crohns disease (CD) do not reliably correlate with endoscopic activity. While treating to achieve clinical remission (CR) has neither proven to improve CD outcomes nor alter the natural disease course, it is unclear whether targeting objective measures like mucosal healing (MH) is associated with improved long‐term outcomes.

Management of inflammatory bowel disease with vitamin D: Beyond bone health

A relationship between vitamin D and several disorders, including Crohns disease (CD), has recently been proposed. Vitamin D appears to have several important actions beyond the maintenance of bone health, including various effects on the immune system. Vitamin D deficiency has been implicated in the development of CD, and its analogues may have a role in the treatment of CD. Current research also suggests a role for vitamin D in counteracting some IBD-specific complications, including osteopenia, colorectal neoplasia, and depression. There remains a need for prospective studies to further delineate these relationships. Given current evidence and the apparent safety of vitamin D supplementation, it appears reasonable to screen for and treat vitamin D deficiency in patients with IBD.

Management Strategies to Improve Outcomes of Patients With Inflammatory Bowel Diseases

Strategies for management of inflammatory bowel diseases are shifting from simple control of symptoms toward full control of these diseases (clinical and endoscopic remission), with the final aim of blocking their progression and preventing bowel damage and disability. New goals have been proposed for treatment, such as treat to target and tight control based on therapeutic monitoring and early intervention. For patients who achieve clinical remission, there is often interest in discontinuation of therapy due to safety or economic concerns. We review the evidence supporting these emerging paradigms, the reasons that early effective treatment can alter progression of inflammatory bowel diseases, the importance of examining objective signs of inflammation, and the safety of reducing treatment dosage. We also discuss recent findings regarding personalization of care, including factors that predict patient outcomes and response to therapies, as well as preventative strategies.

Are patients with inflammatory bowel disease at increased risk of coronary artery disease

The inflammatory state of atherosclerosis has been established as those with chronic inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus, who are at increased risk of coronary artery disease. A systematic search was conducted to retrieve high-quality, peer-reviewed studies of inflammatory bowel disease and coronary artery disease. Recent literature supports an association between inflammatory bowel disease and coronary artery disease. While hypertension increases the risk of coronary artery disease in inflammatory bowel disease patients, other typical risk factors have not been confirmed, and markers of inflammation may predict coronary artery disease risk in this population. Common cardiovascular drugs such as statins and angiotensin-converting enzyme inhibitors may have dual potential for controlling inflammatory bowel disease and preventing or treating coronary artery disease. Large, prospective, longitudinal studies can help to determine the true prevalence of coronary artery disease in this population and confirm risk factors. In the absence of such evidence, physicians should be cognizant of increased coronary artery disease risk in inflammatory bowel disease patients without traditional risk factors and consider primary preventive strategies.

Meta‐analysis: colonoscopic post‐polypectomy bleeding in patients on continued clopidogrel therapy

Current guidelines recommend the cessation of clopidogrel therapy 5 days and 7–10 days prior to colonoscopic polypectomy. Recent studies have advocated for continued clopidogrel as post‐polypectomy bleeding (PPB) rates have been similar to those in the general population not on antithrombotic therapy.

Systematic Review and Meta-Analysis: Infliximab or Cyclosporine as Rescue Therapy in Patients With Severe Ulcerative Colitis Refractory to Steroids.

OBJECTIVES:Acute severe steroid-refractory ulcerative colitis (UC) carries a poor prognosis and requires optimal management. A systematic review and meta-analysis were conducted to assess cyclosporine and infliximab (IFX) as rescue agents in patients with steroid-refractory UC.METHODS:A literature search identified studies that investigated IFX and cyclosporine in steroid-refractory UC patients. The primary outcome was short-term response to treatment. Secondary outcomes included the rates of colectomy at 3 months and 12 months, adverse drug reactions, post-operative complications in those who received rescue therapy but underwent colectomy subsequently, and mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) are reported.RESULTS:Overall, 16 studies with 1,473 participants were eligible for inclusion. Among three randomized controlled trials, no significant difference was seen with IFX compared with cyclosporine with regard to treatment response and 3- or 12-month colectomy. Among 13 non-randomized studies, IFX was associated with significantly higher rates of treatment response (OR 2.96 (95% CI 2.12–4.14, χ2=6.50, I2=0%)) and a lower 12-month colectomy rate (OR 0.42 (95% CI 0.22–0.83, χ2=30.94, I2=71%)), with no significant difference seen in the 3-month colectomy rate (OR 0.53 (95% CI 0.22–1.28, χ2=22.73, I2=69%)) compared with cyclosporine. There were no significant differences between IFX and cyclosporine in adverse drug-related events, post-operative complications, or mortality.CONCLUSIONS:In the management of steroid-refractory severe UC, no definitive difference between IFX and cyclosporine is demonstrated by randomized trials, but non-randomized studies suggest that IFX is associated with better treatment response and lower risk of colectomy at 12 months. Prospective studies comparing dose-optimized IFX with cyclosporine are needed.

Anti-TNFα therapies are safe during pregnancy in women with inflammatory bowel disease: a systematic review and meta-analysis.

Background:The use of TNF&agr; antagonists is well described for inflammatory bowel disease (IBD), but their safety profile during pregnancy is yet to be fully elucidated. A systematic review and meta-analysis were performed to identify studies that explored the safety of anti-TNF&agr; therapy during pregnancy in patients with IBD. Methods:A systematic literature search was conducted to identify studies that investigated the pregnancy outcomes among women with IBD on anti-TNF&agr; therapy. The primary outcome was the overall rate of unfavourable pregnancy-related outcomes among women with IBD on anti-TNF&agr; therapy. Secondary outcomes included rates of abortions (spontaneous or elective), preterm delivery, low birth weight, and congenital malformations. Odds ratios (OR) with 95% confidence interval (CI) are reported. Eligible studies used an observational or interventional design, enrolled subjects with IBD on anti-TNF&agr; therapy for at least 1 trimester and compared outcomes with appropriately matched controls. Results:Overall, 5 studies with a total of 1216 participants were eligible for inclusion in the meta-analysis. There was no significant difference in the rates of total unfavourable pregnancy outcomes between pregnant women with IBD who were on anti-TNF&agr; therapy and controls not on anti-TNF&agr; therapy (OR, 1.00 [95% CI, 0.72–1.41]). Similarly, there were no statistically significant differences in the rates of abortion (OR, 1.53 [95% CI, 0.97–2.41]), preterm birth (OR, 1.00 [95% CI, 0.62–1.62]), low birth weight (OR, 1.05 [95% CI, 0.62–1.78]), or congenital malformation (OR, 1.10 [95% CI, 0.58–2.09]). Conclusions:The use of anti-TNF&agr; therapy does not seem to increase the risk of unfavorable pregnancy outcomes among women with IBD, although the optimal timing of therapy through pregnancy and the postpartum period was not assessed in this analysis. These data can help counsel patients around family planning and perinatal management.

Role of probiotics in management of diverticular disease

Patients with diverticular disease may experience a variety of chronic symptoms, including abdominal discomfort, bloating, and altered bowel habit. They are also at risk of complications, including hemorrhage, diverticulitis, abscess, and fistula formation. The potential role of abnormal colonic microflora in the pathogenesis of diverticular inflammation has led to investigation of novel therapies such as probiotics. Probiotics are microorganisms that may be of net benefit to humans when consumed. The rationale and safety of their use in diverticular disease is discussed and current literature is reviewed.