TY - JOUR
T1 - Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis
T2 - the prospective VIEWS pharmacokinetics study
AU - Chaemsupaphan, Thanaboon
AU - Pudipeddi, Aviv
AU - Lin, Hui Yu
AU - Paramsothy, Sudarshan
AU - Kariyawasam, Viraj C.
AU - Kermeen, Melissa
AU - Leong, Rupert W.
N1 - Publisher Copyright:
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
PY - 2025/1/14
Y1 - 2025/1/14
N2 - BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory condition requiring continuous treatment and monitoring. There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown. AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy. METHODS This is a post-hoc analysis of prospective randomized clinical trial (VIEWS) involving UC patients across 8 centers in Australia from 2018 to 2022. Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab. We evaluated vedolizumab serum trough concentrations, presence of anti-vedolizumab antibodies, and clinical outcomes over 48 weeks to assess exposure-response association and impact of thiopurine withdrawal. RESULTS There were 62 UC participants with mean age of 43.4 years and 42% were females. All participants received vedolizumab as maintenance therapy with 67.7% withdrew thiopurine. Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use, with no anti-vedolizumab antibodies detected. Patients with clinical remission had higher trough concentrations at week 48. In quartile analysis, a threshold of > 11.3 μg/mL was associated with sustained clinical remission, showing a sensitivity of 82.4%, specificity of 60.0%, and an area of receiver operating characteristic of 0.71 (95%CI: 0.49-0.93). Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission. CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial. While thiopurine did not influence vedolizumab levels, its withdrawal may necessitate higher vedolizumab trough concentrations to maintain remission.
AB - BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory condition requiring continuous treatment and monitoring. There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown. AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy. METHODS This is a post-hoc analysis of prospective randomized clinical trial (VIEWS) involving UC patients across 8 centers in Australia from 2018 to 2022. Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab. We evaluated vedolizumab serum trough concentrations, presence of anti-vedolizumab antibodies, and clinical outcomes over 48 weeks to assess exposure-response association and impact of thiopurine withdrawal. RESULTS There were 62 UC participants with mean age of 43.4 years and 42% were females. All participants received vedolizumab as maintenance therapy with 67.7% withdrew thiopurine. Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use, with no anti-vedolizumab antibodies detected. Patients with clinical remission had higher trough concentrations at week 48. In quartile analysis, a threshold of > 11.3 μg/mL was associated with sustained clinical remission, showing a sensitivity of 82.4%, specificity of 60.0%, and an area of receiver operating characteristic of 0.71 (95%CI: 0.49-0.93). Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission. CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial. While thiopurine did not influence vedolizumab levels, its withdrawal may necessitate higher vedolizumab trough concentrations to maintain remission.
KW - Antibody
KW - Inflammatory bowel diseases
KW - Pharmacokinetic
KW - Thiopurine
KW - Trough concentration
KW - Ulcerative colitis
KW - Vedolizumab
UR - http://www.scopus.com/inward/record.url?scp=85212686836&partnerID=8YFLogxK
U2 - 10.3748/wjg.v31.i2.101292
DO - 10.3748/wjg.v31.i2.101292
M3 - Article
AN - SCOPUS:85212686836
SN - 1007-9327
VL - 31
JO - World Journal of Gastroenterology
JF - World Journal of Gastroenterology
IS - 2
M1 - 101292
ER -