Exploring Preventive Treatments for Rheumatoid Arthritis

Results from a Phase 2b clinical trial, published today in The Lancet by researchers led by King’s College London, provide hope to arthritis sufferers after the biologic drug abatacept was shown to reduce progression to the agonizing 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 usually begins in middle age, but can affect much younger age groups and so far 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 administered via weekly injections at home or in hospital via drip.

Researchers at King’s College London recruited 213 patients at high risk of the disease to understand whether a one-year treatment with the biologic drug could be used to prevent progression to rheumatoid arthritis .

They recruited men and women over 18 years old with early symptoms such as joint pain but no joint inflammation, and treated half with the drug and the other half with a placebo every week for a year. The study drug was then discontinued and study participants were monitored for an additional 12 months.

After twelve months of treatment, 6% of patients treated with abatacept had developed arthritis compared to 29% in the placebo group. At 24 months, the differences were still significant, with a total of 25% progressing to rheumatoid arthritis in the abatacept group compared to 37% in the placebo group.

Figure:

Figure: Mean change from baseline for secondary outcomes over 24 months. HAQ-Disability index (A), HAQ pain scale (B), EQ-5D (C) and EQ-5D VAS (D), for 24 months. The end of the study and the end of treatment are indicated. The SDs at baseline for these measures are 0.7 for the HAQ Disability Index, 26.7 for the HAQ Pain Scale, 0.10 for the EQ-5D, and 22.3 for the EQ-5D VAS. HAQ=Health Assessment Questionnaire. VAS=Visual Analog Scale.

Professor Andrew Cope, from King’s College London, said: "This is the largest rheumatoid arthritis prevention trial to date and the first to demonstrate that a therapy licensed for use in the treatment of established rheumatoid arthritis is also effective in preventing the onset of the 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 the onset of the disease during the treatment phase, but "which can also relieve symptoms such as pain and fatigue. This is also promising news for the NHS, as the disease affects people as they age and its treatment will become more expensive with an increasingly aging population."

Secondary outcomes from the trial showed that abatacept was associated with improvements in pain, function, and quality of life scores, as well as lower joint lining inflammation scores detectable by ultrasound.

Testimony

Philip Day, a 35-year-old software engineer and founder of FootballMatcher from Eltham, was at high risk of rheumatoid arthritis. Philip, an enthusiastic soccer player, his joint pain deterred him from playing and affected his daily life. He enrolled in the trial in 2018, when he was 30, and was prescribed abatacept.

He said: "The pain became so terrible that I stopped going to football, became lazier and progressively felt worse physically and mentally. The pain was unpredictable, one day it would appear in my knees, the next in my elbows and then on my wrists or even my neck. At that time, my wife and I wanted to have children and I realized that my future was quite bleak if the disease progressed. I always wanted to be the type of father who played soccer with his son and I. I knew that pain would prevent me from realizing that dream.

"Signing up for the trial was a no-brainer; it was a ray of hope in a dark time. Within a few months I had no more aches and pains and five years later I would say I’m cured. Now, I can play soccer with my son three years and lead a normal life.

A year’s treatment with abatacept costs the NHS around £10,000 per patient and is not without risk. Side effects include upper respiratory tract infections, dizziness, nausea, and diarrhea, but are usually mild.

Professor Cope added: "There are currently no medicines available that will prevent this potentially crippling disease. Our next steps are to understand those at risk in more detail so that we can be absolutely sure that those most at risk of developing rheumatoid arthritis receive the medicine. "

Rheumatologist Professor Sir Ravinder N Maini FRS FMedSci FRCP, who was not involved in the research, said: "Professor Cope and colleagues at King’s College London, in collaboration with researchers from the UK and the Netherlands, have published the results of an interesting clinical trial in The Lancet, which shows that it is now possible to prevent the onset of RA, a disease that remains incurable despite great advances in its treatment in the recent past.

"The results clearly show that during the treatment period almost all individuals who received the biologic drug showed no symptoms or signs of RA compared to the control population among many more developed RA. In the 1-year follow-up period without treatment , it is interesting to note that some seemed to go into remission.

"Disease prevention is, of course, a highly desirable goal to prevent the ravages of disabling RA, which is associated with a significant social and financial burden. Many additional questions arise from this important study. For example, does this preventive approach Will it be safe and expensive? Is it effective if continued long term or can the selection of appropriate populations be refined so that only those likely to benefit most are treated with a short course?