Professor Lyn March AM and Craig WIllers discuss The Australian Arthritis and Autoimmune Biobank Collaborative (A3BC), their vision for Autoimmune disease and the future of treatments, medical advances and ultimately a cure for the debilitating group of musculoskeletal diseases.

1. 8 SEPTEMBER 2018 | RHEUMATOLOGY REPUBLIC
FUTURISM Research
I
t all started when a rheumatoid arthritis
patient of Lyn March’s asked her what her big
dream for the specialty was. As things stood,
the professor of rheumatology was thinking
she would probably retire in the next five years.
Consequently, she was planning on winding
down and not taking on any more PhD
students. But having devoted more than 20
years to rheumatology, she did have some
aspirations for this area of medicine that she
wished she could see become reality.
One of these was a nationwide biobank built
by clinicians and researchers that would be
a comprehensive database including a broad
range of patient information – everything from
a patient’s genomic information to their sleep
patterns, diet and medication.
To date, nothing of this scope had happened
in Australia, not in any specialty let alone
rheumatology.
As one of Australia’s leading rheumatology
experts, Professor March was involved
in teaching, researching and guideline
development. One project she was involved
in the Australian Rheumatology Association
database.
“We had this vision to collect information on
inflammatory arthritis biologic therapies and
follow their patient outcomes,” she says.
“For a while we’d been thinking how much
stronger if we had biospecimens, and we
actually had tissue, cells and genetic material.”
Then she got the call.
Her patient and his family had a trust, and
they wanted to make this idea a reality.
“I was totally blown away by their generosity,”
Professor March recalls.
The patient himself had been effectively
treated with precisionmedicine, but when
he looked around at what was happening in
Australia he was struck by the lack of funding
and recognition given to such n debilitating
condition.
He was asking, “Why doesn’t Australia have a
national institute for arthritis?”, “Why don’t we
fund arthritis in Australia?” she remembers.
So, he and his family decided to give
Professor March and her colleagues several
million dollars to get the idea off the ground,
and to help establish the infrastructure to
help far more patients suffering from similar
conditions.
With any plans for imminent retirement
now out the window, Professor March and
her colleagues began to get excited about the
future of research in the country.
Their frustration of being limited by current
knowledge and resources was now replaced
with enthusiasm.
“We want to cure arthritis,” she says.
Australia has fantastic researchers, but many
of the younger ones haven’t been able to see a
future in rheumatology because the funding
has been thin on the ground, she says. Despite
nice words by politicians, the funding just
doesn’t match the burden these conditions
have on the community, the health system and
the individuals themselves, she adds.
With the help of this philanthropic donation,
the vision for the future is now brighter.
“It started with the philosophy that ...we
wanted to get the right treatment to the right
person at the right time,” she says. “But we also
wanted to start talking about curing arthritis
and other autoimmune diseases.”
Right now, clinicians are treating to target,
but the real goal is getting patients to go into
remission.
Because many of the newer arthritis drugs
are expensive, clinicians need to use them
responsibly.
Patients might be 12 to 18 months into their
disease before they the most effective therapy
for them, and by that stage the disease has
already damaged their joints.
“Our conditions are so heterogeneous.
Everyone is quite different in terms of how their
different types of arthritis progress and people
are also amazingly individual in terms of how
they respond to individual treatment.”
Because of this heterogeneity, it is unlikely
treatments and cures will hinge on the
discovery of a single gene. Instead, the
researchers believe the answer will require a
multiomic approach – that is, understanding
the genome, proteome, epigenome and
microbiome.
But with the right information, Professor
March and her colleagues hope that they
could look at patients and say: “Alright, you’re
secreting this cluster of cytokine, and you’ve got
this particular gut bacteria, let’s use this drug.”
Following on from this philanthropic
donation, other research bodies and
funding agencies have jumped on board to
Much like the thinking around cancer 50 years ago,
the concept of finding cures for autoimmune diseases
is often put in the too-hard basket. But one ambitious
research project is hoping to change that
RUBY PROSSER SCULLY
Biobanks
and the
future
of precision
medicine
ProfessorLynMarch
“Wehadthisvisionto
collectinformation
oninflammatory
arthritisbiologic
therapiesand
followtheirpatient
outcomes.”
,

2. help build the infrastructure. The biobank
goes by the name of A3BC, which stands for
Australian Arthritis and Autoimmune Biobank
Collaborative.
Its national director, Craig Willers, is now in
the process of making the vision a reality. This
involves talking to different stakeholders, trying
to establish funding models and ensuring that
the data they get from different jurisdictions can
be used in the one national database.
He says so far, they’ve been met with support
and enthusiasm.
“Everyone realises that the best way, and
possibly the only way, to make big ground in
both precision and preventive medicine is to
collect as much information as possible,” he
says. “And that’s something that’s not being
done [currently].”
The aim for the A3BC is to include not only
information on the genome, microbiome and
metabolism, but also patient reported outcomes.
The new system will build off the Australian
Rheumatology Association Database, which
collects longitudinal data on quality of life and
other measures of arthritis and health.
Participants will be asked to fill out an
expanded questionnaire, which will probably
take them 45 minutes to an hour, which, in
addition to questions about their disease
and its treatments will ask for dietary and
environmental information, as well as
pregnancy information where relevant.
It is hoped that, in the future, researchers
wanting to investigate a particular group
of rheumatology patients will be able find
the cohort with the necessary criteria in the
dataset, bypassing the time consuming and
expensive process of signing people up, getting
ethics approval and collecting all the material
to perform it if they were starting a trial from
the ground-up.
Those leading the project hope that, by
making the foundations strong enough
through the quality of the information
collected, they can future-proof the biobank
and create it in a way that it outlasts the
individuals themselves.
Mr Willers says that in the next five years, the
team hopes to sign up 20,000 patients to the
biobank, that is 4000 per year.
While they are focusing on conditions
such as rheumatoid arthritis, juvenile
idiopathic arthritis, psoriatic arthritis and
vasculitis in the preliminary stages, he hopes
it will eventually develop to include other
autoimmune and rheumatological conditions
such as osteoarthritis and Sjögren’s syndrome.
The rapidly growing capabilities of
technology and artificial intelligence also
bode well for the future of such a rich data-
source. There’s a kind of “build it and they will
come” approach to the project.
Pointingtosomeofthemanyresearch
questionsthisbiobankcouldbeofvalue,Professor
Marchsaidthatthegutmicrobiomewouldbean
importantavenuetobeginexploring.
The work in fields such as inflammatory bowel
disease have shed some light on how the gut
influences the patient’s response to therapy,
suggesting there might be lessons to be learnt
in terms of how the microbiome affects the
absorption of some of the new oral agents in
rheumatology.
Interesting work around SNPs has suggested
that one small change to the nucleotide on the
DNA could lead to alterations in drug therapy
response. But it’s early days.
To date the bank only contains two tissue
samples. While Professor March is excited
by these early contributions, there’s some
way to go before there exists the wide-scale
database that is needed to bring the much
hoped for insights that will positively affect
clinical practice.
“In the past, ethics commitees have not
wanted to approve fishing expeditions,”
Professor March says. But thanks to the vision
and purpose, some of the many ethics boards
have already given approval in principle to the
use of biobank data for research purposes.
Ongoing funding will be a challenge.
So far, they have had other state and institute
organisations agree to match funding on
certain projects, which will help, but the costs
will be substantial, Mr Willers says.
He says they currently have eight sites around
the country to collect and store the specimens.
The biospecimens themselves could cost
around $350 to $400 to store, which “really adds
up”, Mr Willers says.
But between funding bodies such as the
Centres of Research Excellence, the Medical
Research Futures Fund and the Genomics
Health Futures Mission, Mr Willers says
he’s confident they will be able to cover the
establishment costs. From there, it may be that
when a research group accesses the resources,
they will pay for the costs associated with the
biospecimens.
Aside from ongoing funding there are also
other challenges.
A major hurdle is trying to synch-up databases
across different jurisdictions.
How a local health district in Sydney codes
its data may be entirely different to the way
country South Australia does. Given the dozens
of local health districts around the country,
the difficulty this problem poses should not be
underestimated.
Another potential issue has been the
controversy surrounding the My Health Record.
As privacy concerns related to government-
backed electronic medical records seem be
escalating rather than diminishing, keepers of
similar valuable personal information, such as
those developing the rheumatology biobank,
are under pressure to secure safeguards against
potential misuse and privacy breaches.
This is a good challenge, according to Mr
Willers.
“Obviously we don’t want to be seen to be
taking any risks with sensitive data either,” he
says.
He and his team want to ensure they are
doing their due diligence and addressing any
and all of the requirements set out by different
regulatory authorities and stakeholders.
“We are now at the point of working with each
hospital site and saying, ‘Are there any risks,
because we are chomping at the bit to work
with you’.”
As for clinicians themselves, it’s likely that
each will interact with the biobank in different
ways.
The model is still in development, but the
idea is to allow some clinicians to simply refer
patients on to another clinic where they can
have their information and testing done.
Others might have several patients willing to
be involved and call out a nurse to the clinic to
collect the data there.
Whichever way the process takes place,
Professor March is keen that clinicians are able
to see the fruits of the efforts. This might mean
they receive feedback on the patient’s outcomes,
or very practically, it might mean qualifying for
professional development points.
For patients, Professor March and her
colleagues hope that it will prove to be a
valuable record of the progress of their disease,
enabling them to recognise which treatments
and therapies have been most effective
and providing a means of measuring their
improvement or decline.
While she realises this is an ambitious project,
Professor March and her team are setting their
sights high.
“Often with arthritis and lupus and all the
autoimmune diseases we say ‘this is too hard,
we’ll never cure them’, but [those in] cancer
probably said that 50 years ago as well,” she says.
Most people in the medical community now
consider cancer a potentially curable disease.
It’s time to be bold enough to have that vision
in rheumatology, she says.
“To have a research infrastructure with the
amount of material that we will collect, we
will have the real potential to drill down from
an amazing resource of specimens and data
and information – that’s what is spurring
people on.”
“It will continue to be giving long after we’re
actually here.”
RHEUMATOLOGY REPUBLIC | SEPTEMBER 2018 9
Many ethics boards are now approving the use of biobank data for research purposes
A3BCnationaldirectorCraigWillers
“Everyonerealises
thatthebestway,and
possiblytheonlyway,
tomakebigground
inbothprecisionand
preventivemedicine
istocollectasmuch
informationas
possible.”
,