Clinical study found that RA can be blocked in the preclinical stage

MILAN–A year of treatment with abatacept (Orencia) prevented clinical manifestations of ‘preclinical’ rheumatoid arthritis (RA) from developing in most patients showing signs of impending onset, researchers say. reported here.

In a randomized phase IIb trial in patients at high risk of developing rheumatoid arthritis, only 7 of 110 people assigned to abatacept developed clinical arthritis after 1 year compared with placebo. 30 out of 103 in the group (hazard ratio 0.20, P.=0.0002), according to Andrew Cope, M.D. (MBBS), King’s College London.

But after stopping abatacept for a year, the effects didn’t last, he told conference attendees. European Federation of Rheumatology Societies (EULAR) Annual General Meeting. The following year, 20 more patients in the abatacept group developed clinical arthritis, and he developed 8 in the placebo group.

The Abatacept regimen maintained significant benefit over the 2-year period (HR 0.61, P.= 0.003), the Kaplan-Meier curves for arthritis-free survival converge rapidly near the end, and additional follow-up will likely catch up with the abatacept arm.

At the same time, there were no specific safety issues with abatacept, so there was no apparent reason why this regimen could not be continued longer.

Stopping RA before it really progresses has long been a goal of rheumatologists. Many studies support early and aggressive treatment of rheumatoid arthritis once diagnosed. However, initiating biologic therapy without a formal rheumatoid arthritis diagnosis is never recommended.

Nonetheless, some patients are referred to an arthritis clinic with some joint pain and other features such as rheumatoid arthritis-associated serum biomarkers that suggest a possible progression to full-blown rheumatoid arthritis. I will see a doctor. Wouldn’t it be good to see if aggressive treatment at that stage would prevent this population from going down that path?

That’s exactly what Cope and his colleagues thought a decade ago. Register for current trial In 2014, the research group was called “Arthritis Prevention in the Preclinical Stage of Rheumatoid Arthritis with Abatacept” (APIPPRA). The group explained why they chose Abatacept: 2019 protocol description“Targets the immune response early in the chain of events leading to inflammation in rheumatoid arthritis. It blocks interactions between T cells and antigen-presenting cells, leading to T cell activation, differentiation and effector responses.” It works by attenuating the necessary co-stimulatory signals.”, thereby leading to “downstream immunomodulatory effects on other inflammatory cells of the immune system.”

Researchers recruited patients from 31 centers in the UK and the Netherlands. To be eligible, participants must have arthralgia but no synovitis and have positive anti-citrullinated protein antigen (ACPA) antibody and rheumatoid factor (RF) tests or high levels of ACPA. Antibodies (at least 3x the upper limit) had to be shown. normal limit of the assay used if no RF is used). The primary endpoint was development of clinically significant arthritis in at least 3 joints or diagnosis of RA according to standard criteria.

The average age of patients was approximately 48 years, and three-quarters were female. Most had a history of smoking, but less than a third had five or more alcoholic beverages per week. Baseline pain scores averaged approximately 24 on a 100-point scale. Nearly all participants met the threshold for high ACPA antibody levels.

Although the protective effect seen in the primary analysis was not sustained across samples, Professor Cope found one very high-risk subgroup, namely those with some levels of IgG ACPA antibodies who were also positive49. He pointed out that the effect was more pronounced in human patients. The same is true for a range of other biomarkers such as RF, IgA ACPA antibodies, anti-carbamylated protein antibodies, and anti-acetylated peptide antibodies. In this set, only about 10% of patients taking abatacept progressed to clinical arthritis by the end of two years, compared with 50% of those taking placebo.