Abstract Background Patients with primary sclerosing cholangitis (PSC) often undergo orthotopic liver transplantation (OLTx) for end-stage disease. PSC is closely associated with inflammatory bowel disease (IBD), and some patients experience refractory course after OLTx. Upadacitinib (UPA) is a novel, effective, orally administered, selective JAK1 inhibitor introduced for the treatment of ulcerative colitis with limited data on post-OLTx population. This study aims to evaluate efficacy and safety of UPA on post-OLTx PSC patients with IBD. Methods This retrospective, single-centre observational study was conducted at IKEM, Czech Republic. We included all patients with PSC who underwent OLTx and had concomitant IBD, who were started on UPA and followed at our centre. The induction dose of UPA was 45 mg daily for three months for all patients, followed by a maintenance dose of 15–45 mg daily. The partial Mayo score (pMayo) and Mayo endoscopic subscore (MES) were used to evaluate IBD activity at baseline and the end of follow-up. Prednisolone (5–40 mg) was administered to all patients except one, who received budesonide (9 mg) daily. Data were extracted from patients’ medical records and charts and stored in MS Excel. Prism 10 was used for statistical analysis; the Wilcoxon rank test was used to compare pMayo and MES before and after treatment. Results In total, 10 patients were included, with a median follow-up of 13.3 months (range 1.6–21.9). Baseline cohort characteristics are shown in Table 1. There was a significant decrease in the median pMayo score from 5.5 at baseline to 2 at the end of follow-up (p 0.01, Figure 1A). Clinical response was observed in all patients except one, who had no initial response. Follow-up endoscopy was performed in 7 patients. The median MES decreased from 3 at baseline to 0 or 1 in three patients, and from 2 to 1 in the other three patients at follow-up endoscopy, but this change did not reach statistical significance (p = 0.625, Figure 1B). Endoscopic remission was confirmed in two patients. Half of the included patients experienced mild adverse effects: acne, rash, recurrent upper respiratory tract infections, CMV colitis, and mild Covid-19 infection. No serious adverse events were detected. There were no changes in liver enzymes or tacrolimus levels during follow-up compared with baseline. Two of the seven patients with re-PSC showed a tendency for decreased ALP and GGT levels; the other patients had stable liver test results. UPA was discontinued in two patients, one due to adverse events and the other due to primary failure. Conclusion UPA appears to be an effective and safe treatment option for active IBD after OLTx and failure of previous biologic or innovative therapy. Conflict of interest: Dr. Hlavaty, Mojmir: No conflict of interest Brezina, Jan: No conflict of interest Bajer, Lukas: No conflict of interest Trunecka, Pavel: No conflict of interest Hucl, Tomas: No conflict of interest Drastich, Pavel: No conflict of interest
Hlavatý et al. (Thu,) studied this question.