Vedolizumab Therapy in Children With Primary Sclerosing Cholangitis
Data From the Pediatric Primary Sclerosing Cholangitis Consortium
Conflicts of interest: B.G.P.K., Pfizer; K.M.L., Mirum, Albireo, and Retrophin; T.M., Alexion and Genfit; M.R.D., Hightide Biopharma, USA. The other authors report no conflicts of interest.
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ABSTRACT
Objectives:
Most patients with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD). The liver and colon express MAdCAM-1, a target of lymphocyte homing integrins. Vedolizumab (VDZ) is an α4β7 integrin antibody used to treat IBD. We investigated liver outcomes in children with PSC-IBD treated with VDZ.
Methods:
Patients were identified within the Pediatric PSC Consortium, a multicenter research registry. Retrospective demographic, phenotypic, biochemical, radiological, histopathologic and IBD data for up to 1 year of VDZ therapy were collected. Liver biochemical and IBD responses were defined as: a 75% or greater reduction in initial γ-glutamyltransferase (GGT), or a GGT that fell to <50 IU/L and improved Mayo endoscopy grade or IBD activity scores after 9 to 12 months.
Results:
Thirty-seven patients were identified from 19 centers. VDZ was initiated at median age of 16 years [IQR 15–18], 69% were male, 65% had large duct involvement, 19% had (Metavir F3/F4) fibrosis and 59% had ulcerative colitis. Of 32 patients with abnormal GGT at baseline, 22% had a liver biochemical response after 9 to 12 months. For IBD, 32% achieved remission, 30% had a clinical response, and 38% had no response. Final GGT after 9 to 12 months was 51 [IQR 28–71] in IBD patients in remission versus 127 [IQR 63–226] in those with active IBD, (P = 0.066).
Conclusions:
Liver biochemistry worsened over time in IBD unresponsive to VDZ but remained unchanged in IBD patients in remission. VDZ did not improve liver biochemistry in pediatric PSC-IBD. Progressive liver disease may be more common in patients with medically refractory IBD.
