scholarly journals Differences in the placental pharmacokinetics of vedolizumab and ustekinumab during pregnancy in women with inflammatory bowel disease: a prospective multicentre study

2021 ◽  
Vol 14 ◽  
pp. 175628482110327
Author(s):  
Katarina Mitrova ◽  
Barbora Pipek ◽  
Martin Bortlik ◽  
Ludek Bouchner ◽  
Jan Brezina ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Cord Blood ◽  
Bowel Disease ◽  
Tumour Necrosis ◽  
Placental Transfer ◽  
Maternal Blood ◽  
Drug Levels ◽  
Lower Drug ◽  
Inflammatory Bowel ◽  
Necrosis Factor

Background: Vedolizumab demonstrated different placental pharmacokinetics than other immunoglobulin G1 antibodies, leading to lower drug levels in cord blood in contrast to maternal blood at the time of delivery. The placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor agents. Current evidence on the placental pharmacokinetics of vedolizumab and ustekinumab is limited. We aimed to assess the placental transfer of ustekinumab and vedolizumab in pregnant patients with inflammatory bowel disease. Methods: Consecutive women from a prospective observational study who were exposed to ustekinumab or vedolizumab within 2 months prior to conception or during pregnancy were included. Ustekinumab and vedolizumab levels were measured in maternal and cord blood at the time of delivery. Results: Drug levels were available in 31 infant-mother pairs (15 exposed to ustekinumab and 16 to vedolizumab). The median maternal and newborn ustekinumab levels were 5.3 mg/l and 10.3 mg/l, respectively (the median infant-to-maternal ratio was 1.7), while the median maternal and cord vedolizumab levels were 7.3 mg/l and 4.5 mg/l (the median infant-to-maternal ratio was 0.66). The ustekinumab levels in cord blood positively correlated with the maternal levels at delivery (ρ = 0.751, p = 0.001). However, no correlation with the timing of the last drug administration was found. In contrast, the vedolizumab levels in cord blood demonstrated significant positive correlation with the maternal levels (ρ = 0.831, p < 0.001) along with the gestational week of the last infusion (ρ = 0.736, p = 0.001). Conclusion: Vedolizumab demonstrated different placental pharmacokinetics, leading to lower drug levels in cord blood compared to maternal blood at delivery; in contrast, the placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor (TNF) agents.

scholarly journals P574 Incidence and indicators of suboptimal response to tumour necrosis factor antagonist therapy in Chinese patients with inflammatory bowel disease: Results from the EXPLORE study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S483-S484
Author(s):  
J Li ◽  
Z Li ◽  
P Hu ◽  
Z Wen ◽  
Q Cao ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Tumour Necrosis Factor ◽  
Bowel Disease ◽  
Tumour Necrosis ◽  
Retrospective Chart Review ◽  
Chinese Patients ◽  
First Line ◽  
Related Hospitalisation ◽  
Inflammatory Bowel ◽  
Necrosis Factor

Abstract Background Inflammatory bowel disease (IBD) patients may experience a suboptimal response to anti-tumour necrosis factor (TNF) therapy. In China, these data are limited. The EXPLORE study aimed to assess the incidence and indicators of suboptimal response to first-line anti-TNF agents in IBD patients in real-world practice in the newly industrialised countries. Methods The EXPLORE study was a multinational, retrospective chart review study. In the China subgroup, adult patients from 10 centres diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) and who initiated first anti-TNF treatment between March 2010 and March 2015, were included. The cumulative incidence (CI) of suboptimal response was assessed over 24 months since the anti-TNF initiation. The indicators of suboptimal response included: IBD-related hospitalisation, dose-escalation, discontinuation including switch to another anti-TNF, non-biologic therapy augmentation, or IBD-related surgery. Primary non-response (PNR) and secondary loss of response (SLOR) were defined as any suboptimal response indicator at &lt;4 and ≥4 months after anti-TNF initiation, respectively. Results Overall, 287 first-line anti-TNF treated patients (35 UC; 252 CD) were included: male, UC 54.3% (n = 19), CD 74.6% (n = 188); mean (SD) age (years), UC 43.1 (14.2), CD 31.9 (11.3); median (min-max) disease duration (years), UC 1.0 (0–9), CD &lt;1 year (0–21); median (min-max) follow-up (months), UC 27.6 (24–60), CD 40.0 (24–60). At 12 and 24 months, the CI of suboptimal response to first anti-TNF treatment was 51.4% and 75.7% in UC, 45.4% and 57.0% in CD, respectively (Figure 1). The median time to the first suboptimal response was 7.2 months in UC and 14.3 months in CD. The CI of PNR was 31.2% in UC and 33.7% in CD. The CI of SLOR was 29.4% and 64.7% in UC, 17.7% and 35.2% in CD at 12 and 24 months, respectively. The most frequent first suboptimal response indicator was ‘discontinuation of anti-TNF therapy’ in UC patients (56.3%) while for CD patients it was ‘IBD-related hospitalisation’ (56.1%) followed by ‘augmentation with non-biological therapy’ in both cohorts (UC 31.3%; CD 22.8%). Conclusion Approximately three-quarters of UC and over half of CD patients experienced a suboptimal response to their first anti-TNF agent at 24 months. Given the high unmet needs observed with anti-TNF therapies in China, IBD patients may benefit from greater optimisation of care and new biologic options.

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