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. 2021 Jun 1:4:100107.
doi: 10.1016/j.jtauto.2021.100107. eCollection 2021.

Baricitinib and primary biliary cholangitis

Stuart C Gordon  1   2 , Sheri Trudeau  3 , Arie Regev  4 , Jonathan M Uhas  1 , Sujatro Chakladar  4 , Ana Pinto-Correia  4 , Klaus Gottlieb  4 , Doug Schlichting  4
Affiliations

Baricitinib and primary biliary cholangitis

Stuart C Gordon et al. J Transl Autoimmun. .

Abstract

Background and aims: There is an unmet need for alternative treatments for patients with primary biliary cholangitis (PBC) who do not respond to treatment with ursodeoxycholic acid (UDCA). A proof-of-concept study of baricitinib, an orally administered Janus kinase 1 and 2 inhibitor, was initiated to evaluate its use in PBC patients.

Approach and results: Patients with PBC showing inadequate response or intolerance to UDCA were eligible. This was a randomized, double-blinded placebo-controlled trial. Enrollees were assigned 1:1 to baricitinib (2 mg/day) or placebo. Endpoints included change in alkaline phosphatase (ALP), itch Numeric Rating Score (NRS), and fatigue NRS at 12 weeks post-baseline; exploratory markers included high sensitivity C-reactive protein (hs-CRP) and Enhanced Liver Fibrosis (ELF) score.Due to low enrollment, the study was terminated early. Two patients were enrolled and completed the trial; 1 was randomized to receive baricitinib and 1 to placebo. Over the treatment period, the baricitinib-treated patient demonstrated a 30% decrease in ALP and a 7-point improvement in the itch NRS, but a 2-point increase in the Fatigue NRS. Markers of inflammation and liver fibrosis (hs-CRP and ELF score) also improved over the study period. In contrast, the placebo-treated patient showed no improvement in primary or secondary endpoints. A single non-serious treatment-emergent adverse event of moderate sinusitis was reported by the baricitinib-treated patient at day 47.

Conclusions: In a 12-week trial, a patient with PBC showing inadequate response to treatment with UDCA demonstrated a dramatic response to treatment with baricitinib.

Keywords: 12-Week; Itch; Jak1/2 inhibitors; Liver disease.

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Figures

Fig. 1
Fig. 1
Serum alkaline phosphatase (blue) and liver-specific alkaline phosphatase (green) for primary biliary cholangitis patients treated with baricitinib (A) and placebo (B). ULN and relevant multiples of the ULN are noted. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
See this image and copyright information in PMC

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