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Abatacept found to halt the progression of rheumatoid arthritis in high risk patients

Abatacept can reduce the risk of rheumatoid arthritis (RA) onset in high-risk patients, as well as alleviating clinical symptoms where the condition is more developed, according to a new clinical trial.

Conducted at 14 hospitals across Europe, the trial showed that abatacept, which modulates the activation of T-cells, can prevent the development of the disease in patients with preclinical rheumatoid arthritis.

After six months of treatment, half of patients with clinical signs of rheumatoid arthritis showed a significant improvement in joint inflammation assessed by magnetic resonance imaging (MRI).

The effects of the interventions in both preclinical and clinical rheumatoid arthritis continued throughout a year-long observation phase.

The findings are published in The Lancet and could help establish early pre-clinical interventions in rheumatoid arthritis.

Individuals with anti-citrullinated protein antibodies (ACPAs) and subclinical inflammatory changes in joints are at high risk of developing rheumatoid arthritis, but treatment strategies to intercept this pre-stage clinical disease remain to be developed.

The researchers conducted a randomised, double-blind, placebo-controlled trial at 14 hospitals and community centres across Europe: 11 in Germany, two in Spain, and one in the Czech Republic. Between 6 November 2014 and 15 June 2021, a total of 139 adults with rheumatoid arthritis aged 18 years or over were screened. They all had ACPA positivity; joint pain but no swelling; and signs of osteitis, synovitis or tenosynovitis in their hand which showed up on MRI.

Of these, 100 participants (78% female) were assigned to two cohorts, and 98 participants completed the trial.

Over a period of six months, the first cohort (n=49) was given a weekly subcutaneous dose of 125mg abatacept, and the second cohort (n=49) was given a placebo.

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MRI was used to determine any reductions in inflammatory lesions at six months. All participants were followed up for 12 months after the drug intervention in a double-blind, drug-free observation phase.

After six months, 26% fewer cases of rheumatoid arthritis were diagnosed in people treated with abatacept, and over half of the patients who received the drug showed a significant improvement in joint inflammation when assessed by MRI.

Of those treated with abatacept, 8% of participants (n= 4/49) developed rheumatoid arthritis, compared to 35% (n=17/49) in the placebo group. Reduced inflammation was seen in 57% (n=28/49) of participants in the abatacept group, compared with 31% (n=15/49) in the placebo group.

Improvements in MRI inflammation remained significantly different between the two groups 12 months after the end of the intervention, with 51% of participants in the abatacept group showing improvements compared to 24% in the placebo group.

Progression to rheumatoid arthritis was seen in 35% of participants in the abatacept cohort compared to 57% of participants in the placebo group.

The researchers reported 12 serious adverse events across the trial (n=4/48 in the abatacept group and n=7/49 in the placebo group) and no deaths.

Commenting on the trial, Juan D. Cañete, a clinical rheumatologist at the Hospital Clínic de Barcelona and senior researcher at FRCB-IDIBAPS in Barcelona, said: ‘These results indicate that if we could establish therapeutic interventions in the previous phase of the disease, there could be a window of opportunity to prevent rheumatoid arthritis from developing.’

He added: ‘We believe that this approach could help many people at risk of suffering from the disease.’

In 2023, it was found that patients with rheumatic and musculoskeletal conditions were particularly vulnerable to long-term opioid use with one in three of those with rheumatoid arthritis or fibromyalgia having received long-term prescriptions for these potentially addictive drugs to manage their pain.

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