Abatacept Shows Signal to Delay Onset of Rheumatoid Arthritis

Richard Mark Kirkner

November 08, 2021

Early intervention with the immunomodulator abatacept (Orencia) may enable people at risk for rheumatoid arthritis but who don't yet manifest symptomatic inflammation to either avoid or delay the onset of full-blown, symptomatic rheumatoid arthritis, early results of a European clinical trial have shown.

Dr Juergen Rech

Early results of the ARIAA study, presented at the virtual annual meeting of the American College of Rheumatology, showed that among patients considered at-risk for RA and having arthralgia and subclinical inflammation – considered symptomatic but not having full-blown RA – 61% of those who received a 6-month course of abatacept versus 31% of the placebo group had an improvement in MRI inflammation score (P = .0043), said Juergen Rech, MD, a rheumatologist at Friedrich-Alexander University of Erlangen-Nuremberg (Germany) and University Clinic Erlangen.

"When we actually talk about early treatment, this may be not early enough or at least could be improved," Rech said in an interview when asked what the findings add to the evidence for treating at-risk RA patients before disease onset. "It seems as if we were in the situation of delaying the development of disease or possibly even preventing it in some patients, and in our trial this approach was safe with abatacept."

ARIAA randomized 100 patients to abatacept or placebo at 14 study sites between November 2014 and December 2019. The goal is to treat at-risk patients for 6 months with abatacept, then follow them for 12 months to determine their progression to RA. Rech noted that 8% of patients in the treatment group and 35% in the placebo group developed arthritis (P = .0025).

He noted that the safety profile of abatacept in this patient population was similar to previous trials. "No safety issues emerged," Rech said.

The investigators used MRI to determine the patients' status for arthralgia and subclinical inflammation before enrollment. They had no history of clinically obvious inflammation fulfilling the criteria for RA and no previous treatment with glucocorticoids or disease-modifying antirheumatic drugs.

The results showed that abatacept is superior to placebo in improving subclinical inflammation and in inhibiting the progression to RA in at-risk patients at 6 months, Rech said, but early clinical results of patients in the study who've had 18 months of follow-up, which were not part of the dataset he presented, revealed that time-limited treatment with the immunomodulator has a significant sustained effect on progression to RA. That "means 6 months of treatment with abatacept will delay the development of RA after 18 months," he said.

After the complete 18-month dataset is analyzed, the next step for investigators will be to re-evaluate the ARIAA population, perhaps for genetic markers, Rech said. What would then follow, he said, could be to conduct a larger phase 3 trial, determine the risk factors that drive RA autoimmunity, see if disease progression varies among ethnic groups and people in different geographic regions, and perhaps start a head-to-head trial with rituximab (Rituxan) or an evaluation of combined time-limited abatacept and rituximab in at-risk patients.

"We should think about new strategies, new life-quality questionnaires, new biomarkers and tools for covering and understanding these RA patients at-risk in a better way," Rech said, noting that a European Alliance of Associations for Rheumatology task force has already addressed this topic.

Dr John Isaacs

John D. Isaacs, MBBS, PhD, professor of rheumatology at Newcastle (England) University, said in an interview that ARIAA is the first readout from a number of studies evaluating preemptive treatment to prevent or delay RA onset. "You have to ask a question: Is this just suppressing what's going on?" Isaacs said. "In other words, now that the treatment has been stopped, there's great interest in what happens over the next 12 months of this study. Have we delayed the onset of rheumatoid arthritis or have we actually prevented it? I think that's the $10 billion dollar question of this and similar studies."

Answering that question may be difficult without a known blood biomarker. "That's not a criticism of the trial; we just don't have that scientifically at the moment," Isaacs said. "Until then, it will be difficult to say we have delayed or we have prevented rheumatoid arthritis. My feeling is, even if we delay it 6 months or even a year with safe treatment, that would be worth it."

Bristol-Myers Squibb sponsored the trial. Rech and Isaacs disclosed having financial relationships with Bristol-Myers Squibb and other pharmaceutical companies.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.


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