The largest prevention trial to date suggests potential benefits outweigh the risks.
Abatacept can reduce progression in patients at high risk of developing rheumatoid arthritis, according to a multicentre study led by researchers at King’s College London.
The study, published in the Lancet, adds to those that have reported success in using abatacept to treat early RA, as well as the smaller ARIAA trial which demonstrated potential in preventing RA progression in at-risk patients.
“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,” said chief investigator Professor Andrew Cope of King’s College London in a media release.
“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,” said Professor Cope.
“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.”
The APIPPRA study was conducted across 28 clinics in the UK and the Netherlands. A total of 213 patients were randomised 1:1 to receive 125mg abatacept weekly or placebo for 12 months, with a 12-month follow up.
All patients met criteria for being at high risk of developing RA, testing positive for ACPA and rheumatoid factor (or if negative RF, had ACPA concentrations at least three times higher than normal) and inflammatory joint pain.
The primary endpoint was development of clinical synovitis in three or more joints, or development of RA according to ACR/EULAR 2010 criteria. Secondary endpoints included DAS-28 and the need for DMARDs or corticosteroids.
At the end of the 12 months of treatment, 6% of the abatacept group and 29% of the control group met the primary endpoint. At 24 months, 25% of the abatacept group and 37% of the control group had developed RA.
“The results of this phase 2B study indicate that treatment of adults at high risk of developing rheumatoid arthritis with abatacept reduces progression to clinically apparent arthritis during the treatment phase,” wrote the authors.
“Even after stopping treatment, the number of events in the abatacept group remained lower than the placebo group, suggesting sustained efficacy.”
Compared with placebo, patients taking abatacept had improved pain scores, functional wellbeing and quality of life scores during the treatment period, and had lower scores for subclinical synovitis as detected by ultrasound. However, these differences were not sustained at 24 months.
The authors said this suggests that pathogenic immune responses re-emerge and are not modified permanently by a fixed period of T-cell co-stimulation modulation.
However, they also pointed out that all patients were encouraged to stay in the study for 24 months regardless of outcome, including those who progressed to RA and were taking DMARDs and corticosteroids, which may have reduced differences between the two groups.
Around 90% of patients in both groups experienced adverse events, with infections being the main issue reported. Rates for type of adverse event were similar for both groups, except for gastrointestinal, haematological and neurological adverse events, which were higher in the abatacept group. All serious adverse events were considered unrelated to study medication.
“There are currently no drugs available that prevent this potentially crippling disease,” said Professor Cope.
“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.”
