A drug currently used as a second- or third-line treatment for those with rheumatoid arthritis has shown huge promise as a preventative, stopping the onset of the debilitating disease in 92.8% of at-risk participants after 12 months.
Abatacept, a biologic sold as Orencia in the US, is just one of the drugs used by rheumatoid arthritis (RA) sufferers to manage symptoms such as inflammation and swelling, and is given as self-administered weekly stomach/thigh injections via needle or pen, or through intravenous (IV) therapy in hospital.
But the results from King's College London's Phase 2b clinical trial of 213 participants indicate abatacept has huge potential as a 'preventative', to intercept in the progression of the disease in people who had early RA symptoms such as joint pain. Much like its use in RA patients, abatacept was given to 110 of the trial participants each week for 12 months. Both the abatacept and control cohorts were monitored for 24 months.
Of the 110 people receiving abatacept, the estimated proportion who were still arthritis-free at the end of the year-long treatment was 92.8%, compared to 69.2% in the control group. At 24 months, 27 (25%) of the participants in the abatacept group had progressed to RA, which was significantly less than the 38 (37%) of 103 in the placebo 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 Professor Andrew Cope, from King's College London. "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."
He added that this is also a win for the health system, "as the disease affects people as they age and will become more expensive to treat with a growing aging population."
The randomized, double-blind clinical trial was conducted across 28 hospital-based early arthritis clinics in the UK and three in the Netherlands, and participants with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor and symptoms such as inflammatory joint pain were chosen due to their elevated risk of developing RA.
While side effects noted included upper respiratory tract infections, dizziness and nausea, they were reportedly mild. Meanwhile, secondary outcomes for participants in the abatacept group included significantly reduced pain, and higher function and quality-of-life scores. Ultrasound scans also showed a reduction in joint-lining inflammation.
Trial participant Philip Day had developed severe joint pain that prevented him from playing football and was increasingly interfering with daily life, taking a huge physical and mental toll. He received abatacept for 12 months in 2018, at the age of 30.
"Enrolling in the trial was a no-brainer; it was a ray of hope at a dark time," he said. "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."
While still at trial stage for preventative use, the researchers hope that it can be further tailored to patients to improve efficacy. The results also suggest that the drug may need to be administered beyond 12 months in order to sustain its effectiveness over time.
"There are currently no drugs available that prevent this potentially crippling disease," said 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."
The results of the trial were published in the journal The Lancet.
Source: King's College London