A drug used to treat rheumatoid arthritis could also prevent the disease in individuals deemed to be at risk.
Results from a Phase 2b clinical trial, published in The Lancet by a team led by King’s College London and involving Birmingham researchers, provides hope for arthritis sufferers after it showed that the biologic drug abatacept reduces progression to this agonising chronic inflammatory disease.
Rheumatoid arthritis affects half a million people in the UK and develops when the body’s immune system attacks itself, causing joint pain, swelling and significant disability. The disease most commonly begins in middle age, but much younger age groups can be afflicted, and until now there is no cure or prevention.
Abatacept is currently used as an effective second or third line treatment for people living with established rheumatoid arthritis and is given by weekly injections at home or in hospital via a drip.
The research team recruited 213 patients at high risk of the disease to understand whether a year-long treatment of the biologic drug could be used to prevent progression to rheumatoid arthritis. They recruited men and women over the age of 18 with early symptoms such as joint pain but no joint swelling, and treated half with the drug and half with a placebo every week for a year. The study drug was then stopped, and study participants monitored for a further 12 months.
After twelve months of treatment, 6% of patients treated with abatacept had developed arthritis compared to 29% in the placebo arm. By 24 months, the differences were still significant, with a total of 25% progressing to rheumatoid arthritis in the abatacept arm compared to 37% in the placebo arm.
This trial is important because it is the largest study examining prevention of rheumatoid arthritis to date and uses advanced imaging to understand the full extent of joint inflammation during the study. This gives the study researchers significant power to understand who, when and how to target people at risk of arthritis.
Secondary outcomes for the trial showed that abatacept was associated with improvements in pain scores, function and quality of life measurements, as well as lower scores of inflammation of the lining of joints detectable by ultrasound scan.
As the study was aimed at preventing arthritis from developing, it was crucial for researchers to know without doubt whether there was arthritis in the joints when participants developed any new symptoms.
To be able to precisely assess this, the team scanned patient’s joints using state-of-the-art ultrasound technology designed by Professor Andrew Filer’s team at the University of Birmingham. Ultrasound is significantly more sensitive than examination by clinical staff, and it’s also fast, painless and has no side effects.
Professor Filer’s group worked with international collaborators to create a protocol for joint scanning for the trial, and then trained all 28 participating units across the UK and the Netherlands. The group has extensive experience in scanning patients in the earliest phases of arthritis as part of the NIHR Birmingham Biomedical Research Centre longitudinal arthritis cohorts.
Philip Day, a 35-year-old software engineer and founder of FootballMatcher from Eltham, was at high-risk for rheumatoid arthritis. A keen football player, Philip’s joint pain deterred him from playing and affected his day-to-day life. He was enrolled in the trial in 2018, at the age of the 30, and was prescribed abatacept.
He said: “The pain got so terrible I stopped going to football, and I got lazier and felt progressively worse physically and mentally. The pain was unpredictable, it would show up in my knees one day, my elbows the next, and then my wrists or even my neck. At the time, my wife and I wanted to have children and I realised my future was pretty bleak if the disease progressed. I’d always wanted to be the kind of dad that played football with his son and I knew the pain would stop me from realising that dream.
“Enrolling in the trial was a no-brainer; it was a ray of hope at a dark time. Within a few months I had no more aches or pains and five years on I’d say I’ve been cured. Now, I can play football with my three-year-old son and have a normal life.”
One year’s treatment with abatacept costs the NHS about £10,000 per patient and is not without risk. Side effects include upper respiratory tract infections, dizziness, nausea and diarrhoea, but these are generally mild.
Professor Andrew Cope, from King’s College London, said: “This is the largest rheumatoid arthritis prevention trial to date and the first to show that a therapy licensed for use in treating established rheumatoid arthritis is also effective in preventing the onset of disease in people at risk. These initial results could be good news for people at risk of arthritis as we show that the drug not only prevents disease onset during the treatment phase but can also ease symptoms such as pain and fatigue. This is also promising news for the NHS as the disease affects people as they age and will become more expensive to treat with a growing aging population.
“There are currently no drugs available that prevent this potentially crippling disease. Our next steps are to understand people at risk in more detail so that we can be absolutely sure that those at highest risk of developing rheumatoid arthritis receive the drug.”
Professor of Translational Rheumatology
Staff profile for Professor Andrew Filer, Professor of Translational Rheumatology, Department of Inflammation and Ageing, College of Medicine and Health, the University of Birmingham.
