Study results showed that Entyvio decreased alkaline phosphatase serum levels by 20% in a subset of patients with concomitant inflammatory bowel disease and primary sclerosing cholangitis.
While Kate D. Lynch, MD, from the University of Oxford in the United Kingdom, and colleagues observed no evidence of a biochemical response to Entyvio (vedolizumab, Takeda Pharmaceuticals), treatment was well-tolerated, and the overall response was the same as expected for patients without PSC.
“Patients with more aggressive disease, such as the presence of cirrhosis and potentially those with a raised ALP at baseline were more likely to respond,” they wrote. “In addition, the proportion of patients experiencing a liver-related outcome appears to be in keeping with the natural history of disease.”
Of the 102 patients in the study, approximately 20% had cirrhosis at baseline and 64.7% had ulcerative colitis. During a median of 412 days, 44 patients discontinued treatment due to a lack of efficacy (72.3%) and adverse events (13.6%).
Twenty-one patients experienced a drop in ALP of 20% or more from baseline at last follow-up, while 39 patients had stable ALP and 42 patients had an increase of 20% or higher. Both univariate and multivariate analyses showed that cirrhosis correlated with an ALP drop of 20% or higher (OR = 4.7; 95% CI, 1.61-13.76).
Women were more likely to achieve the 20% or more drop in ALP (29% vs. 15.6%). The same was seen in a comparison of patients with cirrhosis vs. those without cirrhosis (42.9% vs. 13.8%).
The researchers noted that it would be difficult to conclude whether the correlation between cirrhosis and ALP reduction was a true finding or spurious as they could not show a connection between changes in ALP and changes in liver synthetic function such as bilirubin and international normalized ratio. However, there was no indication that patients with cirrhosis had worse outcomes during treatment.
“Although spontaneous normalization of ALP has been described in a variable proportion of patients with PSC irrespective of endoscopic intervention or use of [ursodeoxycholic acid], the natural history of PSC is for the ALP level to remain relatively stable or increase slightly over time,” Lynch and colleagues wrote. “Therefore, the observed reduction in ALP ... in a subset of patients on vedolizumab suggests a possible therapeutic signal worthy of additional investigation.” – by Talitha Bennett
Disclosure: Lynch reports travel support from Takeda Pharmaceuticals. Please see the full study for all other authors’ relevant financial disclosures.