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The ARCADIA consortium has been enabled by £3m of funding from Arthritis UK. It brings together leaders in the field of inflammatory arthritis research from the UK and Italy to answer the important question of 'When has remission been achieved?' This could help people to safely stop their medications at the right time in the future.
There is no accurate biological test for determining when a patient with inflammatory arthritis is truly in a state of disease-free remission. This means that clinicians, alongside patients and their families, make treatment decisions without having a full picture of whether their arthritis has been resolved in the joints. Some individuals remain on treatment unnecessarily and others come off treatment only to quickly relapse.
Researchers and clinicians, from the Kennedy Institute, the Universities of Birmingham, Glasgow, Newcastle, Bristol, and Liverpool, alongside University College London Great Ormond Street Hospital, Kings College London and Università Cattolica del Sacro Cuore, aim to undertake clinical studies to accurately determine the true absence of disease.
Chris Buckley, Kennedy Professor of Translational Rheumatology and Director of Clinical Research at the Kennedy Institute explained: 'The ARCADIA consortium is based on over a decade of collaboration between many of the organisations involved. History teaches that cure requires an understanding of cause. This partnership has a bold aim: to determine the cellular cause of inflammatory forms of arthritis across the lifespan so that we can deliver a cure for people with arthritis.'
Inflammatory arthritis includes several different types of arthritis including rheumatoid arthritis and juvenile idiopathic arthritis (JIA). Collectively, it affects more than 1 in 100 people, not only in later life but also in childhood and adolescence. The disease can have a profound impact on daily life and sometimes leads to long term disability. It occurs when the immune system mistakenly attacks the joints, causing inflammation experienced as swelling, stiffness and pain.
This challenge was driven by patients who told researchers they seek long-term freedom from inflammatory arthritis. Patients spoke of their frustration that symptoms such as pain and fatigue persist despite treatment, reported side effects of long-term treatment, and highlighted fears over when it is safe to stop treatment.
Professor Adam Croft, principal investigator of the study, Arthritis UK Professor of Rheumatology at the University of Birmingham and researcher at the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, through which the study will be delivered, explained the current method of determining remission was not fit for purpose: 'Many people with inflammatory arthritis undertake treatment, usually for many years, to control their disease. Increasingly these drugs eliminate the noticeable symptoms of arthritis, and this is often called remission. However, we know that many people who are in remission and stop their medications quickly experience a relapse. This suggests that current drugs fail to alter the underlying causes of disease, and that the causes of disease remain present even in the absence of troublesome symptoms.
Therefore, we believe the current definition of remission is not fit for guiding treatment decisions.'
Using the data generated, the team will develop tools to accurately determine risk of relapse, allowing patients and physicians to make informed treatment decisions. It would benefit patients like Catherine Wright, 52, from Belfast who has lived with arthritis for 50 years, having been diagnosed with JIA and uveitis at 18 months.
'I have found a biologic that is working well and I am physically active and enjoying life to the full. But I have been on a variety of different drugs over the years and have had many joint injections and the side effects haven't been pleasant. Even now my husband says to me 'have you taken your biologics this week?' He is the one who gets it out of the fridge and reminds me.
'So, the idea of a permanent long-lasting remission is very exciting indeed. Research is all about hope and this is giving me hope.'
The current approach to treatment of inflammatory arthritis in all age groups focuses on early and intensive treatment to bring symptoms under control. This can lead to patients needing to take more than one drug, sometimes delivered via infusions in hospital as an outpatient or regular injections. Throughout, patients require frequent blood tests, monitoring and help managing side-effects which can vary in severity.
Professor Lucy Wedderburn of University College London Great Ormond Street Institute of Child Health and Consultant of Paediatric Rheumatology at Great Ormond Street Hospital, said the research was vital to reducing the burden that treatment places on individuals, particularly children. She said: 'Despite considerable advances in the treatment of inflammatory arthritis over the past two decades, little progress has been made towards addressing the problem of when young people can safely stop their medication. These issues significantly impair the wellbeing of people living with arthritis and their families. Particularly for children, ongoing medication and side effects can take a significant toll.'
This has been the case for Katie Eldridge, 30, from Kent, who was diagnosed with JIA at 5 years old and has been on and off methotrexate, and now adalimumab, for most of her life.
'I've been declared in remission twice before and taken off medication. I then hit stressful periods in my life, and my arthritis flared straight back up. This happened during my A-levels and in my mid-20's just before COVID.
'Flares can have a significant impact on your physical and mental health, for me, my abilities and ambitions started to diminish. If remission is defined, then it would remove the fear of unexpected flares and allow for a positive recovery.'
Patients representing a breadth of ages will be recruited in the UK and Rome. Tissue samples will be obtained at different stages of disease, treatment and remission, using ultrasound-guided collection of tissue samples for minimal discomfort to patients. The samples will be analysed to better understand the differences between those and healthy joints and investigate how to return diseased tissue to a healthy state.
Dr Marie Falahee of University of Birmingham explained the importance of listening to patient voices when developing a new definition of remission. She said: 'Our patient partners have told us that the current definition of remission is too narrow and doesn't consider overall and ongoing well-being, including the considerable side effects and risks associated with long-term drug treatments. As part of ARCADIA, we will investigate patient perspectives and collaborate with patient research partners to ensure that a new definition of remission better serves the priorities of all people with inflammatory arthritis.'
As well as helping to guide treatment decisions, the outcome of this study will dramatically advance understanding of inflammatory arthritis. This understanding is key to developing new treatments and accelerating the journey to a cure.
Deborah Alsina MBE, chief executive of Arthritis UK, which is funding the consortium, said the charity was grateful to play its role in bringing together a dream team to undertake this pivotal piece of research: 'The crux of the matter is we still lack an understanding of the root causes of inflammatory arthritis which is not only impeding our ability to define remission, but also our ability to find a cure. While there have been significant advances in treatment with the discovery of biologics in recent decades, we are still treating symptoms. To put it another way, it is like spraying the weeds in the garden, but the roots remain out of sight in the soil.
'We are fortunate to have brought together world leading experts in their field to undertake this foundational piece of research which will transform our understanding of inflammatory arthritis and create a springboard for researchers worldwide into new treatments.'
The five-year research study will begin this autumn.