GLIMMER: A Randomized Phase 2b Dose-Ranging Trial of Linerixibat in Primary Biliary Cholangitis Patients With Pruritus

Levy, Cynthia; Kendrick, Stuart; Bowlus, Christopher L.; Tanaka, Atsushi; Jones, David; Kremer, Andreas E.; Mayo, Marlyn J.; Haque, Nazneen; Maltzahn, Robyn von; Allinder, Matthew; Swift, Brandon; McLaughlin, Megan M.; Hirschfield, Gideon

doi:10.1016/j.cgh.2022.10.032

Cited by 37 publications

(75 citation statements)

References 19 publications

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“…However, individually, maralixibat’s AEs rate was significantly higher than placebo (RR: 1.61, 95% CI: 1.00-2.58) 8. The most common AEs reported in the 3 trials were gastrointestinal side effects, particularly diarrhea 8,9,40. When combining the 2 seladelpar trials, we found no significant difference in the number of AEs reported compared with placebo (RR: 0.93, 95% CI: 0.76-1.13).…”

Section: Resultsmentioning

confidence: 61%

Pharmacological Therapy of Pruritus in Primary Biliary Cholangitis

Medina-Morales

Bernal

Gerger

et al. 2022

Journal of Clinical Gastroenterology

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Goals: We aim to summarize the current management of pruritus in primary biliary cholangitis (PBC) by evaluating the efficacy and safety of pharmacological therapies. Background: Pruritus is a common symptom of PBC, and evidence regarding the most effective antipruritic agents available is lacking. New pharmacotherapy for PBC has shown promising antipruritic effects. Study: We performed a systematic literature review and meta-analysis including all available double-blind, randomized, placebo-controlled clinical trials that evaluated the efficacy of pharmacotherapy for the symptomatic management of pruritus in PBC. Pruritus was assessed as either a change from baseline or a postintervention score. Results: We included 33 studies and 20 medications. Using the visual analog scale, cholestyramine did not significantly improve pruritus compared with placebo [standardized mean differences (SMD): −0.94, 95% CI: −2.05 to 0.17], whereas rifampin and nalfurafine hydrochloride both significantly improved pruritus (SMD: −3.29, 95% CI: −5.78 to −0.80; n=23 and SMD: −0.58, 95% CI: −1.04 to −0.12). In addition, Bezafibrate and linerixibat significantly improved pruritus (SMD: −1.05, 95% CI: −1.41 to −0.68; n=110 and SMD: −0.31, 95% CI: −0.62 to −0.04, respectively). This effect was also present within the subgroup analysis by pruritus scale, where both bezafibrate and linerixibat significantly improved pruritus compared with placebo (SMD: −1.09, 95% CI: −1.54 to −0.65; P<0.001; visual analog scale; as postintervention score and SMD: −0.31, 95% CI: −0.62 to −0.01; P=0.04; numeric rating scale; as a change from baseline score, respectively). Conclusions: Bezafibrate and Linerixibat are potential second-line antipruritic medications for PBC, particularly those with moderate to severe pruritus.

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Section: Resultsmentioning

confidence: 61%

Pharmacological Therapy of Pruritus in Primary Biliary Cholangitis

Medina-Morales

Bernal

Gerger

et al. 2022

Journal of Clinical Gastroenterology

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“…No serious adverse events were present and the main side effects was diarrhea [74]. Another, but larger placebo-controlled trial found that GSK2330672 was not significantly different versus placebo [75].…”

Section: Asbt Inhibitorsmentioning

confidence: 95%

Current Therapies for Cholestatic Diseases

Méndez-Sánchez¹,

Coronel-Castillo²,

Ordoñez-Vázquez³

2023

Preprint

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Cholestasis is a condition defined as an abnormal decrease of bile flow due to progressive pathological states or cholestatic liver diseases that affect the biliary tree at intrahepatic and extrahepatic level. It induces complications such as cirrhosis, liver failure, malignancies, pruritus, fatigue, bone disease and nutritional deficiencies that merit close follow-up and specific interventions to improve quality of life. Furthermore, cholestasis can progress to end-stage liver disease and represents an entity with high morbidity and mortality; and economic burden, Therefore, it is important that clinicians understand the treatment options for cholestatic liver diseases. This review addresses the pathophysiology of cholangiopathies, a general view of current treatments and their molecular targets, and a specific review of those groups of drugs. The objective is to provide clinicians with an overview of the current treatment of cholangiopathies based on evidence on its efficacy and safety.

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“…Full details of study design, eligibility criteria, endpoints, and statistical analyses have been published in detail elsewhere 30 . Briefly, GLIMMER was a multicenter, double‐blind, randomized, placebo‐controlled, Phase IIb study conducted between January 11, 2017 and April 15, 2020.…”

Section: Methodsmentioning

confidence: 99%

“…One such IBAT inhibitor, linerixibat, is a minimally absorbed oral small molecule, which has been shown to decrease pruritus in patients with PBC 29 . The global Phase IIb GLIMMER trial (GSK study 201000; NCT02966834) further explored the efficacy and safety of linerixibat versus placebo, and reported dose‐dependent reductions in pruritus favoring twice‐daily (BID) dosing over 12 weeks of linerixibat therapy following a 4‐week placebo run‐in, with corresponding improvements in sleep interference and HRQoL 30 . In addition to improvements in mean worst daily itch (MWDI) score, post hoc analysis showed that linerixibat improved monthly itch scores, which may be a better correlate of patient experience (and is also the primary endpoint accepted by regulatory agencies for Phase III investigation) 30 …”

Section: Introductionmentioning

confidence: 99%