Summary Background Anti‐tumour necrosis factor (TNF) agents are effective in Crohn's disease but some patients lose response and require alternative biologic therapy. There are few data on comparative effectiveness of vedolizumab and ustekinumab in this setting. Aim To compare the effectiveness of ustekinumab and vedolizumab in anti‐TNF‐refractory Crohn's disease over 12 months. Methods Patients commencing ustekinumab or vedolizumab for anti‐TNF‐refractory Crohn's disease with minimum follow‐up of 12 months were included. The primary outcome measure was the difference in steroid‐free remission rates at end of induction (2 months) and at 12 months. We also assessed rates of clinical response and remission, treatment persistence, surgery and adverse events in both groups. We performed logistic regression analysis to assess factors associated with steroid‐free remission and clinical response and remission. Results We included 85 patients commencing vedolizumab and 45 commencing ustekinumab. In an unadjusted model, rates of steroid‐free and clinical remission were significantly higher among ustekinumab‐treated patients. After adjusting for confounders, steroid‐free remission was higher among ustekinumab‐treated patients at 2 months (odds ratio, OR 2.79, 95% confidence interval, CI 1.06‐7.39, P = 0.038) and 12 months (OR 2.01, 95% CI 0.89‐4.56, P = 0.095). More patients treated with ustekinumab remained on therapy at the end of 12 months (84.4% vs 61.5%, P = 0.007). Conclusions Ustekinumab appeared more effective in treating anti‐TNF‐refractory Crohn's disease and more patients persisted with therapy.

No abstract

No abstract

role than previously thought. We have now investigated whether IKKa represents a potential therapeutic target for IBD using murine epithelial intestinal organoids. Methods Intestinal crypts were harvested from C57BL/6J mice (n=3) and cultured into enteroids in 3D using a Matrigel matrix. Enteroids were either untreated or administered 0.6 mM of IKKa inhibitor SU1433 on day 3 after passage and stimulated with 30 ng/ml TNF on day 4. Enteroid morphological changes were assessed daily using the Enteroid Circularity Score. Immunohistochemistry for active caspase-3 and Ki-67 was performed to assess apoptosis and cell proliferation. Enteroids were harvested at 3, 6, 24, and 48 hours after stimulation and RT-qPCR was performed to determine the expression profiles of selected inflammation-related and non-canonical NF-kB related target genes.Results Enteroids pre-treated with SU1433 and then stimulated with TNF were protected against enteroid rounding compared to TNF treatment alone. There was also a marked decrease in active caspase-3 positive apoptotic cells 48 hours following TNF in the SU1433 pre-treated group compared to the TNF only group. At the 3, 6, 24 and 48 hour time points NF-k B2, TNF, CXCL9 and ICAM-1 expressions were significantly increased compared to TNF-naïve groups, however there was no significant difference between the SU1433+TNF and TNF only treatment groups. Conclusions TNF induced enteroid rounding and promoted the expressions of several inflammation related genes in the NF-kB signalling pathways. Pharmacological inhibition of IKKa prevented TNF-induced enteroid rounding. This was associated with a significant decrease in apoptosis on histology. Together, our findings suggest that IKKa may be a potential therapeutic target for the prevention of IBD relapse.

Introduction: Community acquired SRVI increase hospital referrals, hospitalization and ICU admissions resulting in high morbidity and mortality during winter season. As there are no defined preventative or treatment measures for most of the SRVI, there is increasing burden on health service resources during SRVI season. This analysis was carried out to evaluate the SRVI incidence, risk factors, impact on mortality and changes in incidence trends over 9 year period in immunocompromised cancer patients. Methods: 2906 cancer patients (haematology: n=1098, 37.8%, lymphoma: n=643, 22.1%, other cancers: n= 1156, 40.1%) treated from January 2006 to January 2015 who had respiratory virus PCR were evaluated. Patients with haematological cancers included ALL (n=137), AML (n=338), Myeloma (n=396), CLL (n=131) or other cancers (n=96) [median age: 50 yr., 5-87, Male: 692, Female: 406). Common solid tumour diagnosis included cancer of Breast (n=280, 24.0%), GI tract (n=207, 17.8%), Lung (n=190, 16.3%), Genitourinary (n=180, 15.5%) or other sites (n=299, 25.7%), [Males: 461, Females: 695; median age: 55 yr., range: 6-89]. Patients with haematological malignancies were younger than patients with other cancers (median age: 50 yr. vs. 55 yr., p<0.001). 804 patients (27.7%) had stem cell transplant. Incidence was compared to the seasonal incidence of SRVI reported by NHS England. All patients with respiratory symptoms who had viral PCR requested on throat and nose swab were included. A total of 10,025 samples were evaluated. Results: In patients with malignancy, the season for ParaFlu, Rhinovirus, Metapneumovirus and FluA lasted longer than in general population (average: 2 months, started early and ended later). Incidence of RSV (6.2%, 4.9%, 1.6%, p=0.001), Adenovirus (1.3%, 1.7%, 0.33%, p=0.004), Rhinovirus (16.6%, 19.9%, 8.5%, p=0.001) and ParaFlu (7.4%, 6.3%, 2.6%, p=0.057) was higher in hematology and lymphoma patients. Incidence of PCP was higher in oncology patients (15.1%, 7.2%, 9.6%, p=0.001). Incidence of PCP was higher with increasing age (5.8% age< 50, 12.2% age>50 yr., p=0.001). Rhinovirus (18.7% age<25 yr., 12.3% age >75 yr., p=0.001) and ParaFlu (8.1% age <25 yr. vs. 6.1% age >25 yr., p=0.02) was higher in younger patients. Stem cell transplant increased risk of RSV (6.8% vs. 3.5%, p=0.001), Adenovirus (1.7% vs. 0.6%, p=0.001) and ParaFlu (8.1% vs. 0.23%, p=0.001) but risk of PCP (7.7% vs. 11.8%, p=0.0001) was lower. Risk of positive PCR for any respiratory virus was higher with increasing age, hematological cancers, and use of stem cell transplant. Surprisingly, diagnosis of CLL and Myeloma did not increase SIRV risk. Thirty-day mortality was higher in patients who had SRVI (p=0.041). Mortality was higher in patients with solid tumours (p<0.0001), RSV infection (p<0.001), FluA (p0.02), PCP (p<0.001), non-SCT patients (p<0.0001) and older age. Except for increasing incidence of PCP in Oncology patients no annual variations in the incidence of specific pathogens was seen. Conclusion: This is one of the first reports that compares incidence of SRVI in patients with cancer to that in general population. The analysis of SRVI using PCR based diagnosis demonstrates that incidence of SRVI in cancer patients show different trends than in general population. SRVI season lasts longer and RSV, FluA and PCP contribute to 30-day mortality. Increasing PCP incidence in patients with solid tumours raises the questions about need to use of PCP prophylaxis in all these cases. Disclosures Somervaille: Novartis: Consultancy, Honoraria; Imago Biosciences: Consultancy. Bloor:Janssen: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Consultancy, Speakers Bureau; Gilead: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees.