Vedolizumab Therapy is Ineffective for Primary Sclerosing Cholangitis in Patients With Inflammatory Bowel Disease: A GETAID Multicentre Cohort Study

Abstract

Background Whether vedolizumab may be effective as a treatment for primary sclerosing cholangitis [PSC] in patients with inflammatory bowel disease [IBD] remains controversial. Methods We performed a retrospective observational study of consecutive patients with IBD and PSC, treated with vedolizumab for at least 30 weeks in 22 centres of GETAID from January 2015 to June 2016. The outcomes included a decrease in the serum alkaline phosphatase [ALP] concentration of at least 50% from baseline to Week 30 or 54, a change in any serum liver enzymes concentrations, and an assessment of the efficacy and safety of vedolizumab in IBD. Results Among 75 patients with active IBD and PSC treated with vedolizumab, 21 patients discontinued vedolizumab before Week 30 [due to lack of efficacy in 19 and malignancy in two patients]. In the remaining 54 patients, a decrease in the serum ALP concentration of at least 50% from baseline to Weeks 30 and 54 was observed in four [7%] and four [11%] patients, respectively. No significant change was observed in serum liver enzyme concentrations at week 30 or 54. After a median follow-up period of 19.4 [14.0–29.9] months, nine cases of digestive neoplasia [colorectal neoplasia in seven and cholangiocarcinoma in two] were reported. Conclusions In patients with IBD and PSC, vedolizumab did not improve serum liver enzyme concentrations at week 30 or 54. Nine cases of digestive cancer occurred during the follow-up period, confirming the need for a tight surveillance programme in this population.

Assessment of extraintestinal manifestations in inflammatory bowel diseases: A systematic review and a proposed guide for clinical trials

“…34,46,51,53 A Jadad score ¼ 4 was assigned to the RCT. 42 Among the studies evaluated through the NOS scale there were four low (8.9%), 19,35,39,43 15 moderate (33.3%) 18,21,23,25,30,33,38,40,41,44,45,[47][48][49][50] and 25 high quality studies (55.6%) 4,20,22,24,[26][27][28][29]31,32,34,36,37,46,[51][52][53][54][55][56][57][58][59][60][61] ( Supplementary Material Tables 1 and 2).…”

“…The diagnostic approach was mainly based on clinical evaluation 4,[18][19][20][21][22][23][24][25]60 even if a considerable percentage of patients underwent biochemical and imaging tests. 4,19,[23][24][25][27][28][29][30][42][43][44][46][47][48][49][50][52][53][54][55][56][57][58][59][60][61] TNF inhibitors were the main biologic drugs for the treatment of EIMs and the response to therapy was primarily assessed through clinical data. Importantly, anti-TNF agents were confirmed to be effective in patients with EIMs, achieving a clinical response in over 50% of cases (except for PSC).…”

“…31 Ursodeoxycholic acid (UDCA) was also administered in six trials (46.1%). 52,[54][55][56][57]61 The response to treatment was evaluated in only four articles through clinical assessment and biological decrease of ALP levels. 31,57,60,61 In all studies, biologics had no impact on the PSC course (Table 4).…”

“…Liver biopsy should not be systematically performed, but it should be reserved for doubtful situations, small duct PSC or overlap syndrome. 4,28,[52][53][54][55][56][57][58][59]61 In addition, clinical examination, ALP levels and MRI or ERCP should be used for the hepatological follow-up of PSC patients. 31,57,60,61…”

Autoimmune hepatitis, primary sclerosing cholangitis, and inflammatory bowel disease. Sequential overlap syndrome: a twist to the mosaic of autoimmunity

“…On the contrary, it has been shown that active screening using MRCP in patients with There are studies underway to evaluate the efficacy of vedolizumab in patients with PSC, but results are controversial (22)(23)(24)(25). Despite an excellent safety profile, most of them fail to demonstrate a significant biochemical improvement of liver tests.…”