The burden of ulcerative colitis (UC) in relation to disease severity is not well documented. This study quantitatively evaluated the relationship between disease activity and quality of life (QoL), as well as health care utilization, cost, and work-related impairment associated with UC in an Australian population. A cross-sectional, noninterventional, observational study was performed in patients with a wide range of disease severity recruited during routine specialist consultations. Evaluations included the Assessment of Quality of Life-8-dimension (AQoL-8D), EuroQol 5-dimension, 5-level (EQ-5D-5L), the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ), and the Work Productivity and Activity Impairment (WPAI) instrument. The 3-item Partial Mayo Score was used to assess disease severity. Health care resource utilization was assessed by chart review and patient questionnaires. In 175 patients, mean (SD) AQoL-8D and EQ-5D-5L scores were greater for patients in remission (0.80 [0.19] and 0.81 [0.18], respectively) than for patients with active disease (0.70 [0.20] and 0.72 [0.19], respectively, both Ps<0.001). IBDQ correlated with both AQoL-8D (r=0.73; P<0.0001) and EQ-5D-5L (0.69; P<0.0001). Mean 3-month UC-related health care cost per patient was AUD $2914 (SD=$3447 [mean for patients in remission=$1970; mild disease=$3736; moderate/severe disease=$4162]). Patients in remission had the least work and activity impairment. More severe UC disease was associated with poorer QoL. Substantial health care utilization, costs, and work productivity impairments were found in this sample of patients with UC. Moreover, greater disease activity was associated with greater health care costs and impairment in work productivity and daily activities.

Biologic therapies have revolutionized the management of inflammatory bowel disease [IBD], but primary and secondary non-responses occur in a significant proportion of patients. Therapeutic drug monitoring [TDM] now has an established role in the treatment algorithm for managing secondary loss of response to anti-tumour necrosis factor [anti-TNF] agents during maintenance therapy. Data to support the use of TDM in the management of secondary loss of response to vedolizumab and ustekinumab are emerging. The potential to prevent primary non-response to biologic agents during induction is of equal, and potentially greater, clinical importance. Again, most data supporting the use of ‘proactive' TDM during induction pertains to the use of anti-TNF agents, but signals of efficacy for the use of TDM during induction with other biologic classes are now appearing. This review aims to summarize data on the use of TDM during induction to prevent pharmacokinetic primary non-response to all three classes of biologic therapy currently available for the treatment of IBD.

Background: Clinical application of therapeutic drug monitoring (TDM) to optimise anti‐TNF therapies in patients with IBD depends upon target ranges.Aims: To review methodology used to determine therapeutic ranges and critically compare and contrast its application to infliximab and adalimumab.Methods: A systematic review was performed, and relevant literature was summarised and critically examined.Results: Upper limits of the therapeutic range are determined by toxicity, a plateau response and cost. Lower limits are determined by optimal concentration on the target of action in vitro and/or in vivo, or by correlation of drug levels with clinical efficacy using area‐under‐receiver‐operator‐curve (AUROC) analysis. In 43 studies, there were huge variations in time at which infliximab and adalimumab levels were measured, the end‐points used (clinical remission to mucosal healing), the clinical setting (active disease vs maintenance phase) and the reason for TDM (proactive vs reactive). In the maintenance phase for infliximab, lower trough limits 2.8‐5.7 µg/mL are reported depending upon end‐points used, with consistent AUROC 0.68‐0.77. Adalimumab TDM targets are even less consistent with a lower limit 5.9‐11.8 µg/mL (AUROC 0.66‐0.83) in some studies, but no cut‐off can be identified that is significantly associated with outcome in others, related to inherent pharmacokinetic and pharmacodynamic differences, and heterogeneity of study design.Conclusions: Evidence for exposure‐response relationship is stronger for infliximab than adalimumab. Due to heterogeneity in settings for drug level measurements, therapeutic ranges vary. These factors need to be taken into account when interpreting the evidence and extending this to therapeutic strategies for IBD patients.

Summary: 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 clearanceMethods: 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.

Inflammation plays an important role in the pathogenesis of atherosclerosis. The link between rheumatoid arthritis (RA) and an increased risk of cardiovascular disease and mortality is well established; however, the association between inflammatory bowel disease (IBD) and cardiovascular risk is controversial. Arterial stiffness is both a marker and risk factor for atherosclerosis. Here we aimed to 1) compare circulating markers of inflammation and endothelial dysfunction, traditional cardiovascular risk factors, and arterial stiffness between RA and IBD to help to understand their different associations with cardiovascular disease; 2) assess the impacts of circulating markers of inflammation and endothelial dysfunction, and traditional risk factors on arterial stiffness. Patients with RA (n = 43) and IBD (n = 42), and control subjects (n = 73) were recruited. Plasma inflammatory markers and von Willebrand factor (vWF) were measured by Multiplex assays or ELISA. Arterial stiffness was determined by brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) was measured. Framingham Risk Score (FRS) was calculated, and other traditional risk factors were also documented. Plasma levels of several inflammatory markers and vWF were significantly but comparably elevated in RA and IBD compared with controls, except for a higher level of C-reactive protein (CRP) in RA than IBD. Compared to controls, FRS, body mass index, waist circumference, and triglycerides were increased in RA, but not in IBD. baPWV did not significantly differ among 3 groups, while ABI was modestly but significantly lower in IBD than controls. Circulating markers (macrophage migration inhibitory factor, tumour necrosis factor-α, CRP, and vWF) were significantly associated with baPWV. However, traditional risk factors (age, systolic blood pressure, body mass index, diabetes and triglycerides) were the parameters associated with baPWV in multiple regression analyses (overall r = 0.866, p < 0.001). RA has a higher level of CRP and more pronounced traditional cardiovascular risk factors than IBD, which may contribute to the difference in their associations with cardiovascular disease and mortality. Traditional risk factors, rather than inflammation markers, are major predictors of arterial stiffness even in subjects with inflammatory disorders. Our results point to the importance of modifying traditional risk factors in patients with inflammatory disorders.