Can Abatacept Reverse Early Rheumatoid Arthritis?

Among individuals at high risk for the development of rheumatoid arthritis (RA), treatment with abatacept (Orencia) helped reverse inflammation, with the implication that such treatment may prevent or at least delay the onset of clinical disease, a researcher reported.

High-risk patients in the the study were seropositive, had arthralgia, and showed signs of inflammation on MRI, according to the presentation at the American College of Rheumatology (ACR) virtual meeting.

In a randomized study that included 98 patients who were given abatacept or placebo for 6 months, 61% of those receiving abatacept showed improvement on at least one MRI parameter (synovitis, tenosynovitis, or osteitis) compared with only 31% of the placebo group (P=0.0043), according to Jürgen Rech, MD, of University Clinical Erlangen in Germany.

RA has been shown to have a preclinical phase characterized by the presence of anticitrullinated peptide antibodies (ACPA), subclinical arthritis, and pain. The ACPA antibodies can emerge years before RA is diagnosed, and imaging studies have revealed the presence of subclinical inflammation and even structural lesions during this preclinical phase in some patients.

T cell-mediated B cell activation is a key step in triggering the onset of autoimmune inflammatory diseases such as RA, and interventions that impede this process may be suitable as potential disease inhibitors, Rech suggested.

Abatacept inhibits T cell activation by binding to CD80 and CD86, and therefore may have a preventive role in preclinical RA, he hypothesized.

To test this hypothesis, Rech and colleagues enrolled patients from 14 European sites from 2014 to 2019 who were considered at risk for RA. The primary endpoint was any change at 6 months from a baseline RA MRI Score that had been above zero for synovitis, tenosynovitis, or osteitis. Patients were then followed for an additional year without further treatment.

Patients’ mean age was 50, and the majority were women. Mean baseline pain score was 42.5 on a 100-point visual analog scale, and mean disease activity on a 100-point scale was 42.6.

Not only was the primary endpoint of resolution of any MRI lesion met by twice as many of the abatacept-treated patients, the treatment also significantly lowered the rate of the development of clinical RA. By 6 months, RA had been diagnosed in 34.7% of the placebo group but in only 8.2% of the abatacept group (P=0.0025), Rech reported.

A total of 12 serious adverse events have been reported through 2021, including one case each of gastritis, cellulitis, pneumonia, and prostate cancer. Only the pneumonia was considered as being treatment-related.

“Follow-up research at 18 months will reveal whether the effect of a time-limited intervention with abatacept has a sustained effect on the inhibition of progression to RA,” he said.

And while the latest 18-month efficacy data were not available for inclusion in his ACR presentation, “I did get the results yesterday and these were also significant at 18 months. This means that 6 months of treatment with abatacept can delay or even prohibit the development of RA after 18 months,” Rech concluded.