Interventions to Delay RA Onset

Dr. Deane was lead investigator on the StopRA trial, which examined symptomatic or asymptomatic patients positive for ACPA and without synovitis on clinical exam, giving hydroxychloroquine for 12 months and evaluating at three years.¹¹

“We thought hydroxychloroquine was an important drug to study because rheumatologists commonly already use it in some patients who might have aches and pains and may be antibody positive,” says Dr. Deane. “But it doesn’t look like it works to prevent future rheumatoid arthritis.”

Dr. Emery

Another important study, TREAT EARLIER, looked at methotrexate as a one-year intervention. Methotrexate did not prevent onset of RA at 24 months, although it did improve patient-reported outcomes.¹²

Paul Emery, CBE, FLSW, FRCP, FRCPE, FMedSci, Versus Arthritis Professor at the Leeds Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds, U.K., points out that although this study didn’t meet its primary outcome, it did show delayed onset of RA in the subset of patients who were positive for ACPA. He also adds that many in the field believe that seronegative RA is distinct from seropositive RA in its pathophysiology and should be considered separately.

Trials in Abatacept: APIPPRA & ARIAA

The APIPPRA study follows up on an abatacept study led by Dr. Emery.^1,13 Abatacept is a co-stimulation modulator attenuating naive T cell activation and downstream production of cytokines, and evidence points to a potential role for T cells in the initiation of the immunopathology associated with RA.¹³

APIPPRA is a phase 2b, randomized controlled study in at-risk individuals positive for ACPA who had joint pain but no synovitis on exam. This multi-center study included 110 patients assigned to receive weekly injections of 125 mg of abatacept weekly and 103 patients to placebo. The treatment group received abatacept for 12 months, with another 12-month follow-up period off the study drug. The clinical end point was RA as defined by EULAR/ACR 2010 criteria or clinical synovitis in three or more joints.¹

At 12 months, 29% of patients in the placebo group had progressed to RA, compared with 6% of those in the abatacept group. At 24 months, one year after treatment cessation, 37% of patients in the placebo group had progressed to rheumatoid arthritis, compared with 25% in the abatacept group, meeting the study’s primary end point.¹ Importantly, in ad hoc exploratory analyses yet to be published, participants with the highest levels of ACPA or an extended autoantibody profile at study initiation were more likely to remain arthritis free at 24 months.¹⁴