Stratified medicine in Primary Biliary Cholangitis
Newcastle has led the development and implementation of stratified personalised medicine into normal clinical practice, for the autoimmune liver disease PBC.
Rather than being given a single standard therapy, the type and dose of drugs used is targeted to the specific needs of patients with “step-up” treatment being added in if a more powerful approach is needed to control the disease or its symptoms.
Newcastle leads the UK-PBC platform, a UK-wide consortium of hospitals, universities and patient groups (eg. the PBC Foundation). Funded by the Medical Research Council Stratified Medicine and the NIHR BRC Newcastle, clinical tools to identify high-risk patients have been identified. These include the UK-PBC Risk Score, a predictive model available as an iPhone “app”, as well as a novel, now patented, blood test.
Working with industrial partners, the “step-up” therapies are now in clinical practice. With the PBC Foundation we performed the first ever national audit to assess the effectiveness and reach of the new approaches to treatment.
The exemplar is the second line agent, obeticholic acid (2), which received accelerated approval by the US Food and Drug Administration for the treatment of PBC in 2016, followed by NICE approval in 2017. It is now implemented across the NHS and other health care systems internationally.
A parallel programme is exploring approaches to treating the life-altering symptoms of PBC. This was made possible by our development of the unique disease-specific quality of life measure – the PBC-40. In a joint BRC and Industry funded project we reported the first new therapy for itch in cholestatic liver disease in 20 years (3) which has now progressed to a Phase 3 Newcastle led clinical trial.
More recently, BRC-funded work identifying novel MR approaches to brain function has led to a clinical trial exploring the role of obeticholic acid on cognitive function (memory and concentration abnormality) in PBC and Parkinson’s, linking with the BRC Dementia Theme.
Hirschfield et al. The British Society of gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut 2018; 67:1568-1594. DOI 10.1136/gutjnl-2017-315259
Nevens et al. for the POISE Study Group*. Obeticholic Acid in Primary Biliary Cholangitis / Cirrhosis: A Phase 3 Trial. New England Journal of Medicine 2016; 375:631-643. DOI: 10.1056/NEJMc1611913
Hegade et al. Effect of ileal bile acid transporter inhibitor GSK2330672 on pruritus in primary biliary cholangitis: a doubleblind, randomised, placebo-controlled, crossover, phase 2a study. Lancet. 2017; 389:1114-1123. DOI: 10.1016/S0140-6736(17)30319-7