The EU- and industry-funded RTCURE project’s groundbreaking approach promises to revolutionize treatment of rheumatoid arthritis, which afflicts millions of people across Europe with joint pain, inflammation and bone and cartilage loss. Unlike current therapeutic approaches that target the symptoms of the disease – which occur after the body’s own immune system attacks the synovial tissue that keeps joints moving smoothly – the RTCURE team is focusing on the underlying causes of the disorder.
‘The type of therapy the RTCURE project is aiming to develop may completely change today’s management of rheumatoid arthritis worldwide by inducing drug-free remission that would eliminate symptoms of the disease and remove the need for lifelong treatments for many patients,’ says scientific coordinator Martina Johannesson at the Karolinska Institutet in Sweden.
Although rheumatology researchers have a good understanding of how an overactive immune system causes inflammation in patients with rheumatoid arthritis, the reasons why the immune system starts attacking synovial tissue in the first place are poorly understood. Thus, current therapeutic approaches focus on managing the symptoms by addressing the inflammation, but despite improved drugs, fewer than 20 % of patients achieve sustained remission. The vast majority are dependent on lifelong use of immunosuppressive and anti-rheumatic medications to reduce pain and maintain joint function.
The RTCURE researchers are focusing instead on identifying new treatments capable of altering the fundamental immune processes that cause rheumatoid arthritis, drawing on cutting-edge research into the earliest events in disease progression at the cellular level of individual immune cells.
‘Studies of events that precede the development of joint inflammation demonstrate that different molecular mechanisms may be involved in these early phases of the disease. In RTCURE, we want to identify and treat the disease as early as possible, before any damage occurs. We aim to accomplish this by inhibiting autoimmune responses through treatments that generate immunological tolerance, preventing the immune system from acting against the body’s own cells,’ Johannesson says.
Registering the risks
To achieve that goal the team is analysing biological indicators among groups of people to determine risk factors and their potential susceptibility to developing rheumatoid arthritis. Combined with clinical data, this information will be included in a registry of rheumatoid arthritis risk indicators, providing researchers with uniform information about individuals and the characteristics of immunological changes that could progress into a person developing the disease.
‘The goal is to have a rheumatoid arthritis risk registry that can be used for future research and will lead to insights into new tolerizing therapies that have the potential to reset the part of the immune system that induces the disease,’ the project coordinator says.
The work is being supported by four clinical trials in collaboration with project partners, including major pharmaceutical companies and small and medium-sized enterprises. A Patient Research Partners group, with nine partners from five countries, provides valuable input from patients themselves, contributing important insights and enhancing understanding among researchers.
By studying diverse patients and biomarkers, RTCURE will lay the groundwork for the development and use of different medications based on specific individual disease indicators, enabling targeted and personalized therapy with potential applications in the treatment of other autoimmune diseases in addition to rheumatoid arthritis.
‘The potential impact of RTCURE on the prevention and therapy of rheumatoid arthritis is significant,’ Johannesson says. ‘This treatment approach would prevent many people from developing autoimmune diseases in the first place and enable more effective therapies for current patients, reducing healthcare costs, lost work days and improving quality of life.’