Abstract Background Personalized treatment in IBD, through Therapeutic Drug Monitoring (TDM) is gaining popularity in treatment of Inflammatory Bowel Disease with Anti-TNF-alfa agents. Pharmacokinetic/Pharmacodynamic (PK/PD) thresholds have been well established for anti-TNF-alfa agents, however, such a consensus is still lacking for vedolizumab (VDZ) and ustekinumab (UST). The aim of this study was to identify exposure thresholds for endoscopic remission (ER). Methods PubMed and Embase was searched on the 7th of April 2025, for the following key terms ‘Ustekinumab OR Stelara OR Vedolizumab OR Entyvio’ AND ‘Therapeutic Drug Monitoring OR Exposure-Response’ AND ‘Inflammatory Bowel Disease’ AND ‘Endoscopy’, to find studies identifying exposure-response relationships between drug-exposure and ER. All studies yielded from the search were processed blinded, and in parallel, by two investigators (E.W. and C.F.), using Covidence. Only full-length, original research articles on adults were included. If complicated disease such as fistulizing or stricturing disease was the main scope, articles were excluded. Relevant reviews were screened by one investigator (CF) to reveal relevant studies not found in our search of PubMed and Embase. The median of PK/PD thresholds were chosen as summary statistics of optimal minimal drug-exposure to eliminate the impact of outliers and avoid assumptions on normal distribution of thresholds. Results A total of 282 studies were retrieved, 104 duplicates were removed, 178 abstracts were screened, 88 studies were screened for eligibility. Relevant reviews were also screened for eligible studies that had not been identified in the initial search. A total of 17 studies were included (VDZ n = 8 studies of n = 869 patients, UST n = 9 studies of n = 1.245 patients). Median PK/PD threshold for ER on UST at week 8 was 8,4 mg/mL (ER w8-24), and 3.5 mg/mL during the maintenance phase (ER w16-52). The median PK/PD threshold for ER on VDZ was 27,0 mg/mL at week 2 (ER w14-52), 23,5 mg/mL at week 6 (ER w14-52), 15,3 mg/mL at week 14 (ER w14-54) and 10.4 mg/mL during maintenance (ER w22-52). Conclusion We have found a clear exposure-response relationship for both VDZ and UST, and provide reference values for assessing adequate exposure. These thresholds can be used to guide dosing in select patients. Conflict of interest: Mrs. Frimor, Camilla: Widigson, Ella: No conflict of interest Steenholdt, Casper: Lectures for Takeda, MSD and Janssen-Cilag research grant from Takeda. Duvnjak, Zrinka: No conflict of interest Husinga, Wilhelm: Has received research grants from an industry consortium (AbbVie, AstraZeneca, Boehringer Ingelheim, F. Hoffmann-La Roche, Merck, Novo Nordisk and Sanofi) for the graduate research training program PharMetrX Weber, Franz: No conflict of interest Kloft, Charlotte: CK reports grants from an industry consortium (AbbVie. Astra Zeneca, Boehringer Ingelheim, F. Hoffmann-La Roche, Merck, Novo Nordisk and Sanofi) for the PharMetrX PhD program and from the European Commission within the Horizon 2020 framework program (“FAIR”), all outside the submitted work Ainsworth, Mark Andrew: lectures/consulting for Abbvie, Celltrion, Eli Lilly, Janssen, MSD
Frimor et al. (Thu,) studied this question.