P410 Vedolizumab is safe and effective for IBD, but has no effect on liver biochemistry in patients with concurrent PSC
Christensen B.*1, Micic D.2, Gibson P.R.1, Singh S.3, Bellaguarda E.2, Corsello P.4, Gaetano J.N.5, Kinnucan J.4, Rao V.L.5, Reddy S.2, Yarur A.3, Rubin D.T.5, Pekow J.5
1Alfred Hospital and Monash University, Melbourne, Australia 2Northwestern University Feinberg School of Medicine, Chicago, United States 3Medical College of Wisconsin, Wisconsin, United States 4University of Michigan Health System, Ann Arbor, United States 5University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, United States
Blocking of lymphocyte trafficking is a potential mechanism to alter the disease course of primary sclerosing cholangitis (PSC). We studied the effect of the selective α4β7 integrin antibody, vedolizumab, on liver biochemistry and inflammatory bowel disease (IBD) activity in patients with IBD and PSC (IBD-PSC).
We reviewed electronic medical records of adult patients who had an established diagnosis of IBD-PSC from five tertiary centers. We assessed baseline patient and disease characteristics and treatment exposures. The primary outcome was change in serum alkaline phosphatase at weeks 14 and 30. Secondary outcomes included changes in other liver biochemistries, the Mayo Risk Score for PSC and IBD clinical and endoscopic remission. We also performed a safety analysis for the development of adverse events including liver-related complications.
We identified 34 patients with IBD-PSC. Nine (26%) had a history of orthotopic liver transplant, 7 were on stable doses of ursodeoxycholic acid (UDCA) and 2 patients commenced UDCA during the study period. Median follow-up was 9 (IQR: 7–16) months; 28 (92%) had at least 6 months of clinical follow-up. Serum alkaline phosphatase activities did not significantly decrease with vedolizumab therapy (median 268 (IQR: 105–551) IU/L at baseline versus 249 (IQR: 183–634) IU/L, p=0.9899 at week 30). Of the 18 patients with an abnormal alkaline phosphatase at baseline (>120IU/L), 11 (61%) had improvement with treatment. In these patients, alkaline phosphatase trended down from 475 IU/L (IQR: 241–757) at baseline to 283 IU/L (IQR: 207–658), p=0.267 at week 30 but none of these normalized (Figure 1). Median alkaline phosphatase changes remained similar when patients exposed to UDCA were excluded. Of the 8 patients (31%) with normal alkaline phosphatase at baseline, 4 (50%) had a subsequent increase to abnormal levels by week 30, from a baseline median of 98 IU/L (IQR: 77–102) to 146 IU/L (IQR: 90–203), p=0.036 at week 30 (Figure 2). No significant changes in other liver biochemistries or the Mayo PSC Risk Score were demonstrated at week 30. 55% of Crohn's disease and 21% of ulcerative colitis patients achieved clinical remission at week 30. Seven patients (21%) ceased vedolizumab therapy; one for a deterioration in liver biochemistry thought to be a drug reaction and six for IBD primary non-response. Two patients developed ascending cholangitis but continued vedolizumab.
Vedolizumab therapy in patients with IBD-PSC has little overall effect on liver biochemistry, but is safe and does improve IBD clinical activity. Treatment earlier in the disease course of PSC and assessment of longer-term exposure of lymphocyte trafficking blockade in IBD-PSC remains of interest.