Arun Swaminath

CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22

Intestinal CX3CR1+ mononuclear phagocytes regulate ILC3 in vivo in response to colitis associated microbial signals.

Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response

Background: Intensifying infliximab therapy is often practiced in Crohns disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval‐halving compared with dose‐doubling. Methods: A multicenter retrospective study of CD patients losing response to infliximab was undertaken. The clinical outcome of patients whose infusion intervals were halved (5 mg/kg/4 weeks) was compared with patients treated by dose‐doubling (10 mg/kg/8 weeks). Results: In all, 168 patients were included from 18 centers in Europe, USA, and Israel. Of these, 112 were intensified by dose‐doubling and 56 received interval‐halving strategy. Early response to dose‐escalation was experienced by 86/112 (77%) patients in the dose‐doubling group compared with 37/56 patients (66%) in the interval‐halving group (odds ratio [OR] 1.7, 95% confidence interval [CI] 0.8–3.4, P = 0.14). Sustained clinical response at 12 months postescalation was maintained in 50% of patients in the dose‐doubling group compared with 39% in the interval‐halving group (OR 1.5, 95% CI 0.8–2.9, P = 0.2). On multivariate analysis, predictors of long‐term response to escalation were a nonsmoking status, CD diagnosis between 16–40 years of age, and normal C‐reactive protein (CRP). Conclusions: Dose intensification leads to a sustained regained response in 47% of CD patients who lost response to standard infliximab dose, but halving the infusion intervals is probably not superior to dose‐doubling. Given the costs and patient inconvenience incurred by an additional infusion visit, the dose‐doubling strategy may be preferable to the interval‐halving strategy. (Inflamm Bowel Dis 2012;)

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.

Infliximab-Induced Autoimmune Hepatitis with Successful Switch to Adalimumab in a Patient with Crohn’s disease: The Index Case

Moderate to severe Crohn’s disease (CD) can be successfully treated with anti-tumor necrosis factor (TNF) a-antagonist agents. These agents, such as infliximab, can cause a spectrum of adverse reactions, some of which demonstrate a class effect, while others are agent-specific. One reported rare complication of infliximab in a patient treated for rheumatoid arthritis, is hepatitis [1]. Herein we report a first case of infliximab-associated autoimmune hepatitis in a patient with Crohn’s disease.

The Power of Poop: Patients Getting Ahead of Their Doctors Using Self-Administered Fecal Transplants

The Power of Poop: Patients Getting Ahead of Their Doctors Using Self-Administered Fecal Transplants

When combination therapy isn’t working: Emerging therapies for the management of inflammatory bowel disease

Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.

Cost-effectiveness of QuantiFERON testing before initiation of biological therapy in inflammatory bowel disease.

Background:Anti–tumor necrosis factor &agr; drugs are known to reactivate latent tuberculosis (TB). Current guidelines recommend screening for latent tuberculosis infection, with either tuberculin skin test (TST) or interferon gamma release assays such as QuantiFERON-TB Gold (QFT-G). Given the high rates of anergy to TST among immunosuppressed inflammatory bowel disease (IBD) patients, there is considerable interest in evaluating the superiority of interferon gamma release assays over TST in this patient population to diagnose latent tuberculosis infection. We compared the performance of TST and QFT-G for screening latent TB among immunosuppressed IBD patients based on prevalence, mortality risk from reactivation TB, and costs. Methods:A decision analytical model was constructed to compare 1-year outcomes and costs of using TST or interferon gamma release assay in an immunosuppressed IBD population. Results:Under the base case scenario, for every 1000 patients screened, the QFT-G strategy resulted in 0.53 deaths from reactivation TB compared with 1.92 deaths using TST. The QFT-G strategy results in 1.85 reactivation TB versus 6.7 reactivation TB using TST. The model was not sensitive to background prevalence of latent TB. The cost of QFT-G would have to be more than double for the TST strategy to become more cost effective. QFT-G also remains the cost-effective option unless the sensitivity of the TST improves by 400%. Conclusions:Under a broad range of parameter values, the QFT-G strategy dominates the TST strategy in cost-effectiveness. Consideration should be given to QFT-G as the preferred method of identifying latent TB in all immunosuppressed IBD patients.

Systematic review with meta-analysis: enteral nutrition therapy for the induction of remission in paediatric Crohn's disease

Despite potential adverse‐events in a paediatric population, corticosteroids are used to induce remission in paediatric Crohns disease. Exclusive enteral nutrition also induces remission, but is infrequently used in the USA because corticosteroids are considered the superior therapy. New data have become available since the publication of the most recent meta‐analysis in 2007.

Capsule endoscopy in Crohn's disease: are we seeing any better?

Crohns disease (CD) is a complex, immune-mediated disorder that often requires a multi-modality approach for optimal diagnosis and management. While traditional methods include ileocolonoscopy and radiologic modalities, increasingly, capsule endoscopy (CE) has been incorporated into the algorithm for both the diagnosis and monitoring of CD. Multiple studies have examined the utility of this emerging technology in the management of CD, and have compared it to other available modalities. CE offers a noninvasive approach to evaluate areas of the small bowel that are difficult to reach with traditional endoscopy. Furthermore, CE maybe favored in specific sub segments of patients with inflammatory bowel disease (IBD), such as those with IBD unclassified (IBD-U), pediatric patients and patients with CD who have previously undergone surgery.

Microbial manipulation as primary therapy for Crohn's disease

While antimicrobials are clinically effective in preventing post-operative recurrence, the role for antibiotics in primary therapy for Crohns disease (CD) remains unclear. The recent multicenter phase 2 trial by Prantera et al received wide attention because it demonstrated an increase in the week 12 remission rate in patients with moderately active CD treated with rifaximin and renewed interest in microbial manipulation as primary therapy for CD. In this commentary, we discuss aspects of durability, immune cell polarization, and safety of microbial manipulation as primary therapy for CD.