Exposure-Response to SC Ustekinumab In Moderate-Severe Crohnʼs Disease: Results From the IM-UNITI Maintenance Study

Therapeutic Drug Monitoring of Biologics for Inflammatory Bowel Disease: An Answer to Optimized Treatment?

“…In addition to looking at the range of reported concentration thresholds in IBD, the relationships between concentration thresholds and the observed concentrations in IBD patients who achieved the clinical end points used to define the concentration thresholds were explored. For IBD patients, reported minimum concentration thresholds across biologics were about 70% of the mean concentrations in patients who achieved the desired outcomes to therapy (Figure 3), 29,33,35,39,40,43,44,[46][47][48][49][52][53][54][55] which is close to the average concentration in the overall population receiving the prescribed dose regimen. 28,39,48,52,55 Although this is no substitute for thorough exposure-response analyses, the data support the view that targeting the population mean or median exposure may generally result in efficacious concentrations for biologics in IBD.…”

“…Most of the studies dealt with infliximab and adalimumab, and less data were available for other biologics. Figure 2 shows the ranges of reported trough concentration thresholds for the biologic therapies approved for IBD from published literature, including infliximab, [28][29][30][31][32][33][34][35][36][37][38][39][40][41] adalimumab, [42][43][44][45][46][47][48][49][50][51] golimumab, 52 ustekinumab, 53 and vedolizumab. 54,55 A tabulated list is provided in Supplemental Table S1.…”

Update on TDM (Therapeutic Drug Monitoring) with Ustekinumab, Vedolizumab and Tofacitinib in Inflammatory Bowel Disease

“…However, contrasting with anti-TNF drugs, the addition of an immunomodulators does not appear to influence significantly UST concentrations as discussed below [ 25 ]. There appears to be interdose variation in UST concentrations, thus motivating to do a TDM at the trough of the dose [ 26 ].…”

“…The relationship between UST exposure during the first weeks of treatment (peak concentrations) and outcomes of patients with CD is not perfectly understood. The exposure-response relationship association of UST has been mainly established through the pivotal phase 3 studies called UNITI-1, 2 and IM-UNITI that used a drug tolerant ELISA [ 5 , 25 , 26 ]. Eight weeks after induction, the median concentration of UST were 2.1 and 6.4 μg/mL respectively for the 130 mg and 6 mg/kg dose groups and serum concentrations of the drug correlated with clinical remission at week 8 in both UNITI-1 and -2 [ 5 , 25 , 28 ].…”

“…Eight weeks after induction, the median concentration of UST were 2.1 and 6.4 μg/mL respectively for the 130 mg and 6 mg/kg dose groups and serum concentrations of the drug correlated with clinical remission at week 8 in both UNITI-1 and -2 [ 5 , 25 , 28 ]. UST concentrations from 3.2 to 4 µg/mL were associated with increased rates of clinical remission at eight weeks post induction [ 26 ]. In a recent post hoc analysis from the pivotal UNITI studies (UNITI 1, 2), Adedokun et al, reported that serum concentrations of UST were correlated to the dose administrated and the efficacy of the therapy during induction [ 25 ].…”