A medicine used to treat rheumatoid arthritis may also prevent the condition in at-risk individuals. Researchers led by King’s College London published the results of a Phase 2b clinical trial in The Lancet today, providing hope for arthritis patients by demonstrating that the biologic medicine abatacept slows the progression of this terrible chronic inflammatory illness.
Rheumatoid arthritis affects half a million people in the UK and occurs when the immune system assaults itself, resulting in joint pain, swelling, and substantial disability. The condition typically appears in middle life, but it can affect people of all ages, and there is currently no cure or preventive measure.
Abatacept is currently used as an effective second- or third-line treatment for adults with established rheumatoid arthritis. It is administered weekly via a drip at home or in the hospital.
Researchers at King’s College London enrolled 213 patients at high risk of the condition to see if a year-long treatment with the biologic medication could prevent progression to arthritis.
They enrolled men and women over the age of 18 with early signs such as joint discomfort but no swelling, and treated half with the medicine and half with a placebo weekly for a year. The research medicine was then discontinued, and the subjects were observed for another 12 months.
After twelve months of treatment, 6% of patients receiving abatacept developed rheumatoid arthritis, compared to 29% in the placebo group. By 24 months, the differences remained significant, with 25% of patients advancing to rheumatoid arthritis in the abatacept arm versus 37% in the placebo arm.
Professor Andrew Cope of King’s College London stated, “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.”
Secondary study outcomes revealed that abatacept was related to improvements in pain, function, and quality of life assessments, as well as decreased levels of inflammation of the joint lining visible by ultrasound scan.
Philip Day, a 35-year-old software developer and Football Matcher founder from Eltham, had a significant chance of developing rheumatoid arthritis. Philip, a keen football player, was unable to play due to joint pain, which had an impact on his daily routine. He entered the experiment in 2018, at the age of 30, and was given abatacept.
He also 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 realized my future was pretty bleak if the disease progressed. I’d always wanted to be the kind of dad who played football with his son, and I knew the pain would stop me from realizing 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.”
A year’s treatment with abatacept costs the NHS around £10,000 per patient and is not without risks. Upper respiratory tract infections, dizziness, nausea, and diarrhea are all possible side effects, though they are usually minor.
Professor Cope said, “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.”
Rheumatologist Professor Sir Ravinder N Maini FRS FMedSci FRCP, who was not involved in the study, stated, “Professor Cope and colleagues from King’s College, London, in collaboration with researchers in the UK and Netherlands, have published the results of an exciting clinical trial in The Lancet, which demonstrates that it is now possible to prevent the onset of RA, a disease that remains incurable despite recent advances in its treatment.
“The results clearly show that during the treatment period almost all individuals receiving the biologic drug showed no symptoms or signs of RA compared with the control population among many more developed RA. In the follow-up period of one year off treatment, it is interesting to note that some appeared to go into remission.”
“Prevention of disease is, of course, a highly desirable goal in preventing the ravages of disabling RA, which is associated with a significant social and financial burden. Many further questions arise from this important study. For example, will this preventive approach be safe and cost-effective if continued long term or can the selection of suitable populations be refined so that only those likely to benefit most are treated with a short course of treatment?”
More information: Andrew P Cope et al, Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial, The Lancet (2024). DOI: 10.1016/S0140-6736(23)02649-1 , doi.org/10.1016/S0140-6736(23)02649-1
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