Therapeutic drug monitoring may have a role in treatment decisions in IBD for biologics such as ustekinumab and vedolizumab but not for anti-TNF agents such as adalimumab, findings presented at UEG Week 2020 suggest.
Interim results from STARDUST, a treat-to-target (T2T) trial of ustekinumab in 500 patients with moderate to severe Crohns disease have provided pharmacokinetic and immunogenicity outcomes after induction and initial maintenance treatment, at 16 weeks, when patients in the T2T arm underwent endoscopy to guide dose adjustment.
The results showed that ustekinumab concentrations were positively associated with the proportion of patients achieving an endoscopic response (SES-CD- >50%) at week 16 (51% for the highest drug level quartile vs 22% for the lowest drug quartile). A similar positive association with ustekinumab was seen for rates of endoscopic remission at 16 weeks and in normalistion of CRP.
In a UEG webinar reviewing the presentations, Dr John Nik Ding, a gastroenterologist at St Vincent’s Hospital, Melbourne, noted that a similar positive association between ustekinumab exposure and outcomes was seen in people with ulcerative colitis, in a three year extension arm of the UNIFI study.
As expected, patients in the 12 weekly dosing arm had lower ustekinumab levels than those in an eight-weekly dosing arm. And while there was no trend for drug levels with subjective outcomes such as symptoms, there was a positive association for objective outcomes such as normalistion of fecal calprotectin, he noted.
He also noted that immunogenicity rates were low at all drug levels, at around 5.5%, and most (82%) of the antibody positive patients had low titres.
Dr Nik Ding said a positive exposure response relationships was also seen for vedolizumab in IBD in a study involving 658 patients with IBD. For patients with Crihn’s disease, there were higher rates of endoscopic remission at 52 weeks in those who had higher levels of vedolizumab, he noted. And in patients with ulcerative colitis rates of remission were similarly higher in those with the greater exposure to vedolizumab.
In contrast, other findings presented at UEG 2020 from the SERENE-UC trial showed no clear exposure response relationship for adalimumab in IBD, according to Dr Nik Ding.
Among the key points from an analysis of the TDM arm of the study were the finidng that 64% of patients required dose escalation due to low adalimumab levels, and for UC non-responders at week, 10% gained remission with TDM maintenance regimen.
“In summary of all the TDM studies we have been largely underwhelmed with the pro-active TDM studies that have been published with infliximab and adalimumab,” he said.
“So drug dosing according to TDM may not matter as much with adalimumab.”
“With respect to vedolizumab we are seeing emerging data, we know that exposure-response relationships exist, with week six levels of over 18mcg/ml being quite well associated with clinical remission,” said Dr Nik Ding.
“And for ustekinumab as we may expect as well, we are seeing the same kind of data when it comes to high levels being responsible for higher rates of remission.”