10 March 2021

Biobank paves future for musculoskeletal research

Clinical Research Rheumatoid Arthritis

A new era of precision and preventive medicine in rheumatology is being built on the back of a national data integration and biobanking initiative for arthritis and autoimmune diseases, although the collaborative venture is not without its challenges.

The Australian Arthritis and Autoimmune Biobank Collaborative (A3BC) is bringing together over 60 clinicians across Australia and several leading researchers to realise its vision of an accessible biobank capable of providing data-driven insights and tailored therapies to transform patient care for people living with musculoskeletal disease.

Starting late last year, the A3BC will collect and store biospecimens including routine bloods, synovial tissue and fluid, connective tissue and bone, linking biological data derived from these samples with matched clinical information.

Existing data sources, such as ARAD’s patient-reported outcomes, will be integrated in the A3BC database, along with patient histories and clinical outcomes input by treating rheumatologists and also documented in electronic medical records, plus clinical data from other state and national datasets. 

Data assembled, the holy grail of A3BC will be identifying subsets of patients who respond to certain therapies, and other people with mild disease who could avoid high-dose treatments.

It follows the success of international research consortia, registries and biobanks that have been operating over the past two decades, primarily interrogating cancer genomics for precision oncology with only a few focused on inflammatory diseases

The A3BC initiative, launched nationally last year, was founded by University of Sydney rheumatologist Professor Lyn March AM, with philanthropic seed funding from a patient who trialled three biologics before finding an effective treatment. 

The philanthropist’s experience – all too common among rheumatology patients – is reflected in a core aim of the A3BC: to bring a new level of precision medicine to rheumatology by identifying the most effective therapies for individual patients. 

“We’ve been very fortunate in rheumatology to have this wealth of drugs over these past two decades,” said Professor March. “But it means [as a treating clinician] you never know exactly which one to use.”

Recent research suggests that even with small treatment groups, a multi-omics analysis approach – which involves combining, as A3BC plans to do, data on gene expression, epigenetic changes, proteomics and the microbiome – can clearly distinguish RA patients that will or won’t respond to different anti-TNF therapies. 

Beyond that, predicting which patients are more likely to reach drug-free remission, discovering new biomarkers indicating treatment response and improving classifications of disease subtypes are all possibilities.  

“If people are reasonably represented, if we’ve got the data collected in a standardised way and well documented – essentially, small numbers with a lot of information – we can find answers,” Professor March said.

“And if people are thinking of setting up a study that would be enriched by sharing data or storing biospecimens, then we have the infrastructure to do it.”

Health economic analyses are also on the cards with healthcare and prescription data from the MBS and PBS linked to the database as well.

Strategically, the A3BC plans on expanding the capabilities of existing networks and research groups, such as University of Queensland Professor Ranjeny Thomas’ work, which aims to develop a personalised risk score to identify at-risk people before they develop RA.  

The A3BC will also partner with the Australian Paediatric Rheumatology Group to expand their registry of children and young people with juvenile idiopathic arthritis. 

But all of this would only be possible with buy-in from rheumatologists and data custodians who play a pivotal role in recruiting patients and collecting clinical data, said Dr Craig Willers, A3BC’s national director.

The initiative would need to get more clinicians on board, from both public and private practice, to expand the biobank’s scope and sample size so it had the power to answer complex scientific questions, he said.

Currently, the A3BC network is comprised of eight national biobanking nodes, and recruits patients with RA, PsA, AS, juvenile idiopathic arthritis, and vasculitis, making it the only biobank for chronic disease operating at a national level. 

With additional funding, the network hopes to expand to more than 50 research hubs and include conditions such as OA and lupus. 

“Clinicians have to see its value as well, and encourage their patients to be part of it,” Professor March added. 

In part, that means ensuring the A3BC has the flexibility and capacity to respond to new questions as they emerge, from basic research to clinical practice, and accommodate specific needs as part of clinical trials, Dr Willers said. 

Another major hurdle for A3BC is the decentralised and largely privatised Australian health care system which over the years has made it difficult to recruit large cohorts, said clinician-scientist Professor Matthew Brown, director of the UK National Institute for Health Research’s Biomedical Research Centre at King’s College London.

Australia’s disparate governance and slow rollout of electronic health records with multiple systems involved would also make clinical data collection challenging, Professor Brown said.

While it would still be a few years yet before sufficient samples and data had been collected for the large-scale analyses envisioned by the A3BC, there were other ways that rheumatology stood to gain from establishing a national biobank, Professor March told Rheumatology Republic.

Professor March said she hoped the needs of rheumatology patients were better recognised with funding for specialised support, such as specialist nursing staff.  

“The more you have these activities, the more likely that clinical workforce will be developed as well because there is a perceived need,” she said. 

“If we’re seen as a group that can collaborate and produce meaningful data that governments and healthcare providers can use in decision-making, that makes a case for expanding our resources to help more patients.” 

All things considered, the A3BC could bring about many benefits for rheumatology patients, practitioners and researchers in Australia – so long as the A3BC and its partners can secure funding to sustain its nationwide aspirations.

“With such little research funding at a national level but with the highest healthcare costs as a disease group, it’s really an area that needs more support for innovation,” said Dr Willers.

“The success of the A3BC, and what this could mean as a model for other chronic diseases, depends to a large degree on the ongoing funding we can attract.” 

Biobanking on a national scale takes serious investment, though the benefits are clear to see with the population-based UK Biobank, which has enrolled more than half a million UK citizens since 2006. 

Its broad prospective data has been used, most recently, to determine the effect of multimorbidity in RA; while at the same time, validating findings from other studies that have identified shared risk factors in immune-related diseases to provide the rationale for repurposing some drugs. 

The A3BC initiative, with its focus on arthritis and autoimmune diseases, will be more targeted than the UK Biobank. 

According to Professor Brown, the national collaboration fostered by the A3BC will greatly benefit musculoskeletal disease research in Australia.  

“A3BC’s stable funding and strong engagement with the musculoskeletal research community significantly increase its chances of success,” said Professor Brown.

Reference:

A Review of International Biobanks and Networks: Success Factors and Key Benchmarks https://dx.doi.org/10.1089%2Fbio.2010.0003

Biobanking in health care: evolution and future directions https://doi.org/10.1186/s12967-019-1922-3