Differential Serum-intestinal Dynamics of Infliximab and Adalimumab in Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Therapeutic drug monitoring is used to guide anti-tumour necrosis factor [TNF] therapy. However, the associations between serum drug levels [SDL], TNF-bound, and free anti-TNF in the target tissue are incompletely defined. We aimed to assess the interactions between these parameters in inflammatory bowel disease [IBD] patients. METHODS: ENZYME-LINKED IMMUNOSORBENT: assays [ELISA assays] were used to detect free drug and TNF-drug complexes in intestinal tissues. Concurrent SDL, anti-drug antibodies [ADA], pharmacotherapy, clinical response, endoscopic appearance, and histological severity were determined. Comparisons between anti-TNFs and paired inflamed/non-inflamed tissue were performed. Variables were correlated and potential interactions detected using multivariate analysis. RESULTS: A total of 95 biopsies taken from 49 anti-TNF treated IBD patients [26 receiving infliximab and 23 adalimumab] were studied. Free drug levels were higher in inflamed compared with non-inflamed paired specimens. Tissue free-drug and TNF-drug complexes levels were higher in adalimumab-treated patients. In adalimumab-treated patients, SDL were correlated with free drug, but not TNF-drug complex levels, in both inflamed and non-inflamed segments. In infliximab-treated patients, higher SDL were associated with the presence of tissue free drug in both inflamed and non-inflamed segments, whereas TNF-drug complexes were mostly detected in non-inflamed but not in inflamed tissue. In the presence of ADA, neither free drug nor TNF-infliximab complexes were measured in the tissue. Tissue levels did not correlate well with clinical, endoscopic, or histological scores. CONCLUSIONS: SDL correlated with tissue free drug levels; however, different dynamics were observed for TNF-drug complex levels. Infliximab and adalimumab tissue drug dynamics differ. Better understanding of these interactions may allow future therapeutic optimisation.

Are all vaccines safe for the pregnant traveller? A systematic review and meta-analysis.

Pregnant travellers and their offspring are vulnerable to severe outcomes following a wide range of infections. Vaccine-preventable diseases can have a particularly severe course in pregnant women, but little is known about the safety of travel vaccines in pregnant women. We performed a systematic review of all published literature concerning the safety of vaccines frequently given to travellers such as yellow fever, MMR (mumps, measles and rubella), influenza, Tdap (tetanus, diphtheria and pertussis), meningococcus, hepatitis A and B, rabies, polio, typhoid fever, tick-borne encephalitis and Japanese encephalitis vaccines. We included case series, cohort studies and randomized controlled trials (RCTs). For the meta-analysis, we included only RCTs that compared the administration of a vaccine to placebo or to no vaccine. Outcome measures included severe systemic adverse events, maternal outcomes related to the course of pregnancy, neonatal outcomes and local adverse events. We calculated the risk ratio and its 95% confidence interval as the summary measure. The safety of influenza vaccine is supported by high-quality evidence. For Tdap vaccine, no evidence of any harm was found in the meta-analysis of RCTs. A slight increase in chorioamnionitis rate was reported in 3 out of 12 observational studies. However, this small possible risk is far outweighed by a much larger benefit in terms of infant morbidity and mortality. Meningococcal vaccines are probably safe during pregnancy, as supported by RCTs comparing meningococcal vaccines to other vaccines. Data from observational studies support the safety of hepatitis A, hepatitis B and rabies vaccines, as well as that of the live attenuated yellow fever vaccine. We found little or no data about the safety of polio, typhoid, Japanese encephalitis, tick-borne encephalitis and MMR vaccines during pregnancy.

Standard pre-travel consultation versus shorter consultation combined with smartphone support: a randomized controlled trial.

Immediate and long-term recalls of a pre-travel consultation are suboptimal. We aimed to assess the role of online consultation for travellers.We randomized travellers into two study groups. In the intervention arm, each traveller was given a short pre-travel consultation of 8-12 minutes, combined with the option of smartphone support before and during the trip. In the control arm, each traveller was given a standard length pre-travel consultation of 18-22 minutes. Endpoints included knowledge about potential risks, travellers' satisfaction, time allocated to each traveller and clinical events.We enrolled 75 patients in the intervention group and 74 patients in the control group. Online consultation was used 33 times, by 24 travellers, both before and during the trip. Important health hazards that were addressed included animal and insect bites (8), treatment of diarrhea (4), malaria prophylaxis (2) and altitude sickness prophylaxis (5). Other consultations consisted mainly of reassurances of worried travellers and provision of data. Knowledge about travel-related risks was higher in the control group before travelling (8.86 ± 1.12 vs 8.34 ± 1.32, P = 0.014), and there was a trend towards higher levels of knowledge also during the trip (8.29 ± 1.35 vs 7.89 ± 1.39, P = 0.06). Travellers' satisfaction before and during the trip was similar in both groups: median 10 (10, 10) in both groups before traveling (P = 0.51) and median 9 (8, 10) in both groups during the trip (P = 0.71). In the intervention group, time allocated to each traveller was <12 minutes. There were no differences in the number of clinical events (P > 0.2 for all comparisons).Online WhatsApp support addressed several important travel-related hazards but, when combined with a shortened pre-travel consultation, was associated with a lower level of knowledge about health risks. Therefore, such smartphone support should augment, rather than replace, pre-travel consultation.