A drug already used to alleviate some of the painful symptoms of rheumatoid arthritis might also be effective at stopping it from developing to begin with – potentially saving millions of people from this debilitating condition, suggest British scientists.
The treatment, abatacept, has been part of a trial to test its effectiveness and safety, involving 213 patients at high risk of developing rheumatoid arthritis in the future, based on early symptoms like joint pain.
For the phase 2b clinical trial, 110 participants were randomly selected to be given abatacept, and 103 participants were given a placebo for a year, with the volunteers’ progress then followed up for a further 12 months.
ScienceAlert reports that the results were significant: after the first year, 29% of the placebo group had developed rheumatoid arthritis, compared with only 6% of the abatacept group. After the second year, those stats rose to 37% of the placebo group and 25% of the abatacept group.
“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 Andrew Cope, a rheumatologist from King’s College London who led the study.
“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 like pain and fatigue.”
Rheumatoid arthritis is brought on by the body’s immune system attacking its own tissues, and abatacept works by dampening down the response of T cells, which play a key role in the immune system.
While the results are promising and show some evidence of a lasting effect, further study will be required. The trial only covered two years, so it’s possible that abatacept only delays arthritis rather than prevents it.
“The data indicate that abatacept treatment beyond 12 months might be required to sustain efficacy over time,” write the researchers in their paper. “Intermittent administration at intervals remains to be assessed.”
The abatacept group experienced less pain and inflammation, and scored higher in quality of life measurements. However, it’s also worth noting that the drug can come with mild side effects, including nausea and diarrhoea.
“Rheumatoid arthritis is a chronic disease that can be intensely painful for those who suffer from it – and while we’re still at the early stages in terms of this research, the hope is that abatacept and drugs like it could eventually prevent more suffering,” said Cope.
“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 receive the drug.”
The research was published in The Lancet.
Study details
Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial
Andrew Cope, Marianna Jasenecova, Sumera Qureshi, et al.
Published in The Lancet on 13 February 2024
Background
Individuals with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor, and symptoms, such as inflammatory joint pain, are at high risk of developing rheumatoid arthritis. In the arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept (APIPPRA) trial, we aimed to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with the T-cell co-stimulation modulator abatacept.
Methods
The APIPPRA study was a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial done in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands. Participants (aged ≥18 years) at risk of rheumatoid arthritis positive for ACPA and rheumatoid factor with inflammatory joint pain were recruited. Exclusion criteria included previous episodes of clinical synovitis and previous use of corticosteroids or disease-modifying anti-rheumatic drugs. Participants were randomly assigned (1:1) using a computer-generated permuted block randomisation (block sizes of 2 and 4) stratified by sex, smoking, and country, to 125 mg abatacept subcutaneous injections weekly or placebo for 12 months, and then followed up for 12 months. Masking was achieved by providing four kits (identical in appearance and packaging) with pre-filled syringes with coded labels of abatacept or placebo every three months. The primary endpoint was the time to development of clinical synovitis in three or more joints or rheumatoid arthritis according to American College of Rheumatology and European Alliance of Associations for Rheumatology 2010 criteria, whichever was met first. Synovitis was confirmed by ultrasonography. Follow-up was completed on Jan 13, 2021. All participants meeting the intention-to-treat principle were included in the analysis.
Findings
Between 22 December 2014, and 14 January 2019, 280 individuals were evaluated for eligibility and, of 213 participants, 110 were randomly assigned to abatacept and 103 to placebo. During the treatment period, seven (6%) of 110 participants in the abatacept group and 30 (29%) of 103 participants in the placebo group met the primary endpoint. At 24 months, 27 (25%) of 110 participants in the abatacept group had progressed to rheumatoid arthritis, compared with 38 (37%) of 103 in the placebo group. The estimated proportion of participants remaining arthritis-free at 12 months was 92·8% (SE 2·6) in the abatacept group and 69·2% (4·7) in the placebo group. Kaplan–Meier arthritis-free survival plots over 24 months favoured abatacept (log-rank test p=0·044). The difference in restricted mean survival time between groups was 53 days (95% CI 28–78; p<0·0001) at 12 months and 99 days (95% CI 38–161; p=0·0016) at 24 months in favour of abatacept. During treatment, abatacept was associated with improvements in pain scores, functional well-being, and quality-of-life measurements, as well as low scores of subclinical synovitis by ultrasonography, compared with placebo. However, the effects were not sustained at 24 months. Seven serious adverse events occurred in the abatacept group and 11 in the placebo group, including one death in each group deemed unrelated to treatment.
Interpretation
Therapeutic intervention during the at-risk phase of rheumatoid arthritis is feasible, with acceptable safety profiles. T-cell co-stimulation modulation with abatacept for 12 months reduces progression to rheumatoid arthritis, with evidence of sustained efficacy beyond the treatment period, and with no new safety signals.
See more from MedicalBrief archives:
Rheumatoid arthritis link to increased COPD risk
Arthritis therapy link to cardiovascular disease improvements
Common JAK inhibitors equally effective for RA – Japanese study