Summary Background Vedolizumab is a gut‐selective immunoglobulin G1 monoclonal antibody to α4β7 integrin for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Prospective clinical studies of vedolizumab in pregnancy have not been conducted; therefore, existing safety data of vedolizumab in pregnancy were examined. Aim To assess pregnancy outcomes in females and partners of males who received vedolizumab. Methods All pregnancy data collected during the clinical programme (from 14 May 2007 to 27 June 2013) and in the post‐marketing setting (to 19 November 2015) were analysed. Results Across six studies, there were 27 pregnancies in female participants and 19 pregnancies in partners of male participants. Among 24 vedolizumab‐treated females (23 with CD/UC, one healthy volunteer), there were 11 live births, five elective terminations, four spontaneous abortions and four undocumented outcomes. A congenital corpus callosum agenesis anomaly was reported in one live birth from a healthy volunteer with extensive obstetric history exposed to single‐dose vedolizumab 79 days before estimated conception. Of 19 pregnancies in partners of male participants, there were 11 live births, two spontaneous abortions, three elective terminations and three undocumented outcomes. Post‐marketing reports recorded 81 pregnancies, resulting in four live births, 11 spontaneous abortions and 66 pregnancies that were on‐going or reported undocumented outcomes. Conclusions Initial analysis, limited by sample size and follow‐up, identified no new safety concerns for pregnancy outcomes in females directly or indirectly exposed to vedolizumab. However, vedolizumab should be used during pregnancy only if the benefits to the mother outweigh the risks to the mother/unborn child.

Background Vedolizumab (ENTYVIO) is a humanized α 4 β 7 integrin antagonist approved for the treatment of inflammatory bowel disease, which selectively blocks gut-specific lymphocyte trafficking. We evaluated the risk of opportunistic infections of interest in patients treated with vedolizumab. Methods We determined the frequency of opportunistic infections and tuberculosis in patients receiving vedolizumab in phase 3 clinical trials and post-marketing settings. We also evaluated adverse events reported in the post-marketing setting in patients with a history of or concurrent hepatitis B/C virus infection. Results The incidence of opportunistic infections in patients receiving vedolizumab was 0.7 (GEMINI 1 and 2 clinical trials) and 1.0 (long-term safety study) per 100 patient-years, with 217 events reported in approximately 114,071 patient-years of exposure (post-marketing setting). Most opportunistic infections were nonserious and the majority of patients continued treatment with vedolizumab. Clostridium difficile was the most commonly reported infection, with an incidence rate of 0.5 per 100 patient-years (clinical trials). Tuberculosis was reported at 0.1 per 100 patient-years (clinical trials), with 7 events in the post-marketing setting. No tuberculosis-related deaths were reported in either setting. No cases of progressive multifocal leukoencephalopathy were reported. In 29 patients with a history of or concurrent hepatitis B/C infection in the post-marketing setting, no viral reactivation was observed. Conclusions Clinical trials and post-marketing data showed that the rate of serious opportunistic infections in patients receiving vedolizumab was low and most patients could continue vedolizumab treatment. The frequency of tuberculosis infection was also low and no hepatitis B/C viral reactivation was reported.

Vedolizumab therapy was associated with a reduced likelihood of new/worsening arthritis/arthralgia in CD and no increased incidence of these events in UC. Studies included (ClincialTrials.gov, number): GEMINI 1 (NCT00783718); GEMINI 2 (NCT00783692); GEMINI 3 (NCT01224171).

BackgroundThe acute and chronic leukaemias constitute about 2.5% of all newly diagnosed malignancies and kill over 4000 people/year in the UK, yet there is little accurate up-to-date data on how the incidence of and mortality from leukaemias vary with socio-economic status in the UK. We aimed to quantify the incidence of and mortality from leukaemias in the UK and their variation with gender, age, year of diagnosis as well as socio-economic status.MethodsAll incident cases of leukaemia were identified in 'The Health Improvement Network' (THIN) General Practice dataset. Crude incidence rates and incidence rate ratios (using Poisson Regression) stratified by age, gender, year of diagnosis and socio-economic status were calculated. Median survival and hazard ratios for risk of death (using Cox regression) were then calculated, and stratified in a similar manner.ResultsA total of 4162 cases of leukaemia were identified, 2314 (56%) of whom were male. The overall incidence of leukaemia was 11.25 per 100 000 person-years. The age and gender distributions of ALL, AML, CLL and CML were similar to UK cancer registry data. The incidence of leukaemias was independent of socio-economic class. Median survival from leukaemia was 6.58 years and mortality increased with increasing age at diagnosis. The prognosis in AML was dismal and worsened with increasing socio-economic deprivation. For other leukaemias mortality was independent of socio-economic status.ConclusionThis is the first general population study to describe the incidence of and mortality from leukaemias in the UK by socio-economic status. Similar mortality across socio-economic gradients in the leukaemias studied suggests equal access to and uptake of services. The exception to this was in AML, where poorer survival in AML patients from lower socio-economic classes may represent a class bias in treatment offered and/or greater co-morbidity in these patients, and warrants further exploration.