Abstract Background Primary sclerosing cholangitis (PSC) is an extra-intestinal manifestation of inflammatory bowel disease (IBD) with a prevalence varying across the world, ranging between 0.12%-10.97%(1). PSC-IBD patients are frequently excluded from clinical trials, especially when they develop liver dysfunction or complications. Consequently, the safety and effectiveness of advanced therapies (AT) in PSC-IBD is not fully known. We convened a Research and Development (RAND) appropriateness panel to identify how stages of liver disease may alter clinical decision-making, with a focus on safety of AT and monitoring. Methods We invited 13 Hepatology and Gastroenterology experts in PSC and/or IBD from across the UK. A systematic literature review was performed and disseminated to the panellists, who scored the appropriateness of interventions on a validated scale (1-3 inappropriate, 4-6 uncertain, 7-9 appropriate). Anonymised results were presented and guided a panel discussion at an online meeting. A second survey was then circulated to panellists for re-scoring. A median appropriateness score was calculated for each statement. A disagreement index (DI) rendered the outcome uncertain. Results Multiple clinical scenarios were discussed by the panel, who agreed on the appropriateness of interventions summarised below. IBD management The panel agreed that AT should not be withheld in patients with active PSC-IBD and clinicians should follow IBD standard of care (SOC) for management of loss of response to therapy and endoscopic assessment of response. Faecal calprotectin (fCal) can be raised in PSC, so a change in trend should be utilised rather than responding to a single result. IBD assessment should be multimodal and not rely purely on fCal. Acute severe Ulcerative Colitis should be managed as per standard of care (SOC). Early MDT discussion should be considered after failure of 2 AT, for discussion regarding the risk/benefit of colectomy. Liver monitoring Liver assessment should be done within 6 months prior to AT induction, with blood monitoring within 3 months post-induction and then at least 6 monthly thereafter. Consider 3 monthly monitoring for patients with decompensated cirrhosis or liver transplant (LT). The appropriateness of AT in specific clinical scenarios is shown in figure 1. Nuances in decision making were largely related to concerns for sepsis, thrombosis or excessive immunosuppression. Conclusion We provide guidance on the use of AT in patients with PSC-IBD. Whilst uncertainty remains, there was agreement that optimal control of IBD is key to reducing dysplasia risk, UC flare and preventing liver decompensation. MDT discussion is advised to optimise patient care and ensure appropriate timing of treatment escalation and/or surgery. Reference: 1. Barberio B, Massimi D, Cazzagon N, Zingone F, Ford AC, Savarino EV. Prevalence of primary sclerosing cholangitis in patients with inflammatory bowel disease: A systematic review and meta-analysis. Gastroenterology. 2021;161(6):1865-1877. Conflict of interest: Nayagam, Jeremy: Consultancy and speak fees from Ipsen. Speaker fees from Dr Falk. Meade, Susanna: Speaker fees FalkPharma, Abbvie Conference fees J and J Ad board J and J Athwal, Varinder: No conflict of interest Chimakurthi, Chenchu Ramu: No conflict of interest Culver, Emma: I have received grants/personal fees from Mirum Phamra, Dr Falk, Takeda and Ipsen Dyson, Jessica: Speaker fees for Dr Falk, Intercept, GSK and Ipsen Consultancy fees for GSK, Umecrine and NICE Pavlidis, Polychronis: Advisory services/ speaker fees/ conference sponsorship/ research grants: Abbvie, Alfasigma, DrFalk, J&J, Pfizer, Roche, Takeda, Teva Rimmer, Peter: I have received research funding from F. Hoffman La Roche. I have received educational grants from Abbvie and Johnson and Johnson. I have received speaker fees from Abbvie, Ferring, Johnson and Johnson and Takeda. Rushbrook, Simon: I undertake advisory work from Falk and received funding from IPSEN. Selinger, Christian Philipp: CPS has received unrestricted research grants from Warner Chilcott, Janssen, Galapagos and AbbVie, has provided consultancy to Warner Chilcott, Dr Falk, AbbVie, Takeda, Fresenius Kabi, Eli Lilly, Galapagos, Ferring, Arena and Janssen, and had speaker arrangements with Warner Chilcott, Dr Falk, Galapagos, AbbVie, MSD, Pfizer, Eli Lilly, BMS, UCB, Fresenius Kabi, Celltrion and Takeda. Speight, Ally: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, Lilly, Dr Falk Pharma Janssen Support for attending meetings and/or travel: AbbVie, Dr Falk Pharma Janssen, Tillott’s pharmaceuticals Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: BSG IBD Section Committee (unpaid) Subramanian, Sreedhar: SS has received speaker fees from Janssen, Takeda, AbbVie, Lilly and Dr Falk Pharmaceuticals educational grants from AbbVie and has served on advisory boards for AbbVie, Dr Falk Pharmaceuticals, and Vifor Pharmaceuticals. Thorburn, Douglas: No conflict of interest Joshi, Deepak: I have received grants and/or personal fees from Boston, Cook, Gilead, Ipsen, Mirum and Q3 medical. Trivedi, Palak: No conflict of interest Dr. Kent, Alexandra: I have received honoraria/Consultancy/Sponsorship fees from Lilly, AbbVie, Coloplast, JandJ, Pfizer, Takeda, Tillotts, Dr Falk, Galapagos/AlfaSigma
Nayagam et al. (Thu,) studied this question.