Background Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the efficacy of VDZ at week 14 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Patients at Massachusetts General Hospital and Brigham and Women's Hospital were considered for inclusion. VDZ (300mg) was administered at weeks 0, 2, 6 and 14. Efficacy was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment, along with C-reactive protein (CRP) and decrease of corticosteroid therapy. Clinical response was defined as decrease in HBI ≥ 3 and SCCAI ≥ 3 and remission as HBI ≤ 4, SCCAI ≤ 2 and physician assessment of response and remission. Results Our study included 172 patients (107 CD, 59 UC, 6 IBD-U, male 48.3%, mean age 40 years and disease duration 14 years). Fourteen patients had an ostomy and 9 an ileoanal pouch and only 35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures with ≥ 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and 46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and 29.3% had clinical response and clinical remission at week 14. Adverse events occurred in 10.5%. Conclusions VDZ is safe and well tolerated in refractory IBD patients in a clinical practice with efficacy in UC and CD with responses similar to what was seen in clinical trials.

Background: The impact of pregnancy on levels of biologic agents in patients with IBD is undefined and time to elimination in vedolizumab-exposed infants is unknown. Aims: To determine the effect of pregnancy on infliximab, adalimumab and vedolizumab levels and to study infant vedolizumab clearance Methods: In a prospective observational study, maternal drug levels were measured pre-conception, in each trimester, at delivery and postpartum. The association between drug levels and gestation in weeks was assessed using generalised estimating equation modelling. Infant vedolizumab levels were performed at birth (cord blood), 6 weeks and 3 months or until undetectable. Results: We included 50 IBD patients (23 on infliximab, 15 on adalimumab and 12 on vedolizumab) with at least two intrapartum observations, plus 5 patients on vedolizumab with only mother and baby samples at delivery. Modelling showed no change in adalimumab levels, an increase in infliximab levels of 0.16 (95% CI 0.08-0.24) µg/L/week (P < 0.001) and a decrease of 0.18 (95% CI: −0.33 to −0.02) µg/L/week (P = 0.03) for vedolizumab. In 17 mother-baby pairs, median infant vedolizumab levels at birth were lower than maternal levels (P < 0.05) with an infant:maternal ratio of 0.7 (IQR 0.5-0.9). Vedolizumab was undetectable between 15 and 16 weeks of age in all 12 infants completing follow-up testing. Conclusions: During pregnancy, adalimumab levels remain stable, while infliximab levels increase and vedolizumab levels decrease. However, the increments were small suggesting that intrapartum therapeutic drug monitoring and dose adjustment are not indicated. Unlike infliximab and adalimumab, infant vedolizumab levels are lower in cord blood than in mothers and appear to clear rapidly.

Background & Aims Physicians frequently encounter patients with immune-mediated diseases and a history of malignancy. There are limited data on the safety of immunosuppressive therapy for these patients. Published studies have been small with few events, precluding robust estimates of risk. Methods We searched Medline, EMBASE, and conference proceedings for terms related to immune mediated disease, immune-suppressive therapy, and cancer recurrence from inception to April 2015. We included 16 studies (9 of patients with rheumatoid arthritis, 8 of patients with inflammatory bowel disease, and of patients with psoriasis) and stratified studies by type of immune-suppressive therapy (monoclonal antibodies to tumor necrosis factor [anti-TNF], conventional immune-modulatory agents, or no immune suppression). A random effects meta-analysis was performed to calculate pooled incidence rates as well as risk differences between the various treatments. Results Our analysis included 11,702 persons contributing 31,258 person-years (p-y) of follow up after a prior diagnosis of cancer. Rates of cancer recurrence were similar among individuals receiving anti-TNF therapy (33.8/1000 p-y), immune-modulator therapy (36.2/1000 p-y), or no immunosuppression (37.5/1000 p-y), but were numerically higher among patients receiving combination immune suppression (54.5/1000 p-y) (P>.1 for all). Subgroup analysis of new and recurrent cancers separately, type of immune-modulator therapy, or immune-mediated disease revealed similar results, with no increase in risk. We found similar pooled incidence values for new or primary cancers when immunosuppression was initiated within 6 years (33.6/1000 p-y for immune-modulatory agents and 43.7/1000 p-y for anti-TNF agents) vs more 6 years after the index cancer (32.9/1000 p-y for immune-modulatory agents; P=.86 and 21.0/1000 p-y for anti-TNF agents; P=.43) Conclusion In a meta-analysis of 16 studies, we observed similar rates of cancer recurrence among individuals with prior cancer who received no immunosuppression, anti-TNF therapy, immune-modulator therapy, or combination treatments. Prospective studies are needed to ascertain optimal intervals for re-initiation of immune suppressive therapies for individuals with specific cancers.

SUMMARY BackgroundAnti-tumour necrosis factor a (anti-TNF) agents have been implicated in drug-induced liver injury. There is minimal data on this occurrence in inflammatory bowel disease (IBD) patients.

This study failed to demonstrate a difference between N and T-S groups in their effects on preventing infection in patients with liver cirrhosis. T-S can be considered an alternative first-line therapy for infection prophylaxis.

Rituximab has been used increasingly in the treatment of antibody-mediated rejection (AbMR) in solid organ transplantation despite the absence of clinical trials demonstrating efficacy. A contributor to the growing use of rituximab is an apparent lack of morbidity; and there are no reports of specific opportunistic infections associated with its use in renal transplant recipients. Two cases of Pneumocystis pneumonia (PCP) occurring nearly 3 years after administration of rituximab for refractory AbMR are reported herein. These cases emphasize the need for ongoing vigilant observation in patients who have received rituximab, and highlight the importance of clinical trials to establish the role of rituximab in prevention and treatment of AbMR.

Background It is unclear whether patients with inflammatory bowel disease (IBD) are at increased risk of COVID-19. Objectives This observational study compared the prevalence of COVID-19 symptoms, diagnosis and hospitalization in IBD patients with a control population with non-inflammatory bowel disorders. Methods This multicentre study, included 2733 outpatients (1397 IBD patients and 1336 controls), from eight major gastrointestinal centres in Lombardy, Italy. Patients were invited to complete a web-based questionnaire regarding demographic, historical and clinical features over the previous 6weeks. The prevalence of COVID-19 symptoms, diagnosis and hospitalization for COVID-19 was assessed. Results 1810 patients (64%) responded to the questionnaire (941 IBD patients and 869 controls). IBD patients were significantly younger and of male sex than controls. NSAID use and smoking were more frequent in controls. IBD patients were more likely treated with vitamin-D and vaccinated for influenza. Highly probable COVID-19 on the basis of symptoms and signs was less frequent in the IBD group (3.8% vs 6.3%; OR:0.45, 95%CI:0.28–0.75). IBD patients had a lower rate of nasopharyngeal swab-PCR confirmed diagnosis (0.2% vs 1.2%; OR:0.14, 95%CI:0.03–0.67). There was no difference in hospitalization between the groups (0.1% vs 0.6%; OR:0.14, 95%CI:0.02–1.17). Conclusion IBD patients do not have an increased risk of COVID-19 specific symptoms or more severe disease compared with a control group of gastroenterology patients.

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