Japanese subgroup analysis of GLIMMER: A global Phase IIb study of linerixibat for the treatment of cholestatic pruritus in patients with primary biliary cholangitis

Tanaka, Atsushi; Atsukawa, Masanori; Tsuji, Keiji; Notsumata, Kazuo; Suyama, Akari; Ito, Hiroshi; Das, Sugato; Maltzahn, Robyn von; McLaughlin, Megan M.

doi:10.1111/hepr.13895

Cited by 2 publications

(2 citation statements)

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“…It is possible that clinical variables other than albumin and bilirubin may be found to be significant in a larger symptoms in PBC, 27 although new promising compounds for pruritus are being investigated in clinical trials. 28,29 Meanwhile, the development of new drugs, such as anti-fibrotic drugs, which can improve LT-free survival in the advanced stages of PBC, remains a significant unmet need.…”

Section: Discussionmentioning

confidence: 99%

“…These results indicate the importance of diagnosing patients with PBC at an earlier stage because of the reduced effectiveness of BZF in the advanced disease stages of PBC. Nevertheless, we consider that BZF should be administered to patients with incomplete response to UDCA even at an advanced stage, because BZF is reported to be helpful for reducing pruritus, one of the very annoying subjective symptoms in PBC, 27 although new promising compounds for pruritus are being investigated in clinical trials 28,29 . Meanwhile, the development of new drugs, such as anti‐fibrotic drugs, which can improve LT‐free survival in the advanced stages of PBC, remains a significant unmet need.…”

Section: Discussionmentioning

confidence: 99%

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Determinants of the effectiveness of bezafibrate combined with ursodeoxycholic acid in patients with primary biliary cholangitis

Matsumoto

Hirohara

Takeuchi

et al. 2023

Hepatology Research

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Background and AimsFor patients with primary biliary cholangitis (PBC) exhibiting suboptimal responses to ursodeoxycholic acid (UDCA), obeticholic acid (OCA), and bezafibrate (BZF) are currently used and shown to improve long‐term outcomes. Nevertheless, we encounter patients who die or undergo liver transplantation (LT) even with combination treatment. In this study, we explored prognostic indicators in patients receiving combination treatment of UDCA and BZF.MethodsWe took advantage of the Japanese PBC registry and enrolled patients who received both UDCA and BZF therapy in 2000 or later. The covariates investigated included baseline covariates as well as treatment covariates. Two main outcomes (all‐cause death or LT and liver‐related death or LT) were assessed using multivariable‐adjusted Cox proportional hazards models.ResultsIn total, 772 patients were included. The median follow‐up was 7.1 years. Using the Cox regression model, bilirubin (hazard ratio [HR] 6.85, 95% confidence interval [CI] 1.73–27.1, p = 0.006), alkaline phosphatase (HR 5.46, 95% CI 1.32–22.6, p = 0.019), and histological stage (HR 4.87, 95% CI 1.16–20.5, p = 0.031) were found associated with LT‐free survival. For survival free from liver disease‐related death or LT, albumin (HR 7.72, 95% CI 1.48–40.4, p = 0.016) and bilirubin (HR 14.5, 95% CI 2.37–88.5, p = 0.004) were found significantly associated.ConclusionIn patients with PBC receiving combination therapy, prognostic variables were similar to those in patients receiving UDCA monotherapy. These results indicate the importance of diagnosing patients with PBC at an earlier stage because of the reduced effectiveness of BZF at advanced stages.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Determinants of the effectiveness of bezafibrate combined with ursodeoxycholic acid in patients with primary biliary cholangitis

Matsumoto

Hirohara

Takeuchi

et al. 2023

Hepatology Research

Self Cite

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Pruritus, Fatigue, Osteoporosis and Dyslipoproteinemia in Pbc Patients: A Clinician’s Perspective

Drazilova,

Koky,

Macej

et al. 2024

Gastroenterology Insights

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In this review article, we summarize the most common clinical manifestations of Primary biliary cholangitis (PBC): pruritus, fatigue, osteoporosis, and dyslipoproteinemia and discuss their impact of the patients’ quality of life. More than half of PBC patients suffer from pruritus or fatigue at the time of diagnosis. We discuss the pathophysiological aspects of the PBC clinical manifestations and treatment options. The pathophysiology of pruritus and fatigue is not adequately elucidated, but IL-31 is associated with the severity of pruritus and could be used to objectify the subjective reporting by questionnaires. Although PBC patients suffer from atherogenic dyslipidemia, they do not seem to have a higher cardiovascular risk; however, this observation needs to be clarified by further clinical studies. The second-line of PBC treatment affects pruritus severity: Obeticholic acid (OCA) worsens pruritus while fibrates improve it. Itching can be alleviated by both non-pharmacological and pharmacological approach, however the are multiple barriers to pharmacological treatment. There is no adequate treatment for fatigue today. Treatment of osteoporosis and dyslipidemia is similar for non-PBC patients; stage of liver disease should be considered in treatment. Further research to clarify the pathophysiology and to eventually discover an effective treatment to improve survival and quality of life (especially pruritus and fatigue) in PBC patients is needed.

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Japanese subgroup analysis of GLIMMER: A global Phase IIb study of linerixibat for the treatment of cholestatic pruritus in patients with primary biliary cholangitis

Cited by 2 publications

References 45 publications

Determinants of the effectiveness of bezafibrate combined with ursodeoxycholic acid in patients with primary biliary cholangitis

Determinants of the effectiveness of bezafibrate combined with ursodeoxycholic acid in patients with primary biliary cholangitis

Pruritus, Fatigue, Osteoporosis and Dyslipoproteinemia in Pbc Patients: A Clinician’s Perspective

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