80 CHAPTER 4 study found a significant reduction in at least one MRI parameter (tenosynovitis, synovitis or osteitis) at 6 months in the treatment arm (62% in the abatacept group vs. 31% in the placebo group), indicating improvement in subclinical arthritis. Moreover, at 6 months, fewer patients in the abatacept arm (8.2%; 4 patients) developed RA compared to the placebo arm (34.7%; 17 patients) [60]. Reduced RA development in the treatment arm was still significant one year after stopping treatment (35% in the abatacept group vs. 57% in the placebo group) [61]. The Arthritis Prevention In the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial is a similar study in patients with CSA and presence of both ACPA and RF or with high serum levels of ACPA alone (i.e. three times higher than the upper limit than normal (ULN)). Exclusion criteria include clinical evidence of joint swelling, previous diagnosis of autoimmune disease, use of corticosteroids within 12 weeks before inclusion used to treat musculoskeletal symptoms and current use of cs/ bDMARDs. The study aims to recruit 206 patients who are randomized to either receive weekly subcutaneous injections of 125 mg abatacept for a year or placebo. Patients are followed up for an additional year after the end of treatment. The primary study endpoints are feasibility, efficacy, and acceptability of treatment, and the characterization of immune and inflammatory responses associated with ACPA for the duration of the therapy. Co-primary endpoints are the time to development of clinically apparent synovitis in at least three joints or time to development of RA as defined by the ACR/EULAR 2010 classification criteria. The secondary endpoints of the study are development of RA and assessment of disease activity, the percentage of patients requiring DMARDs, treatment adverse events, and patients’ perceptions. Results are expected to be presented by the end of 2022 [62]. Rituximab Rituximab is a chimeric monoclonal antibody that specifically targets CD20 on B cells, inducing cell death through complement-dependent cytotoxicity and antibody-dependent cytotoxicity [63]. In the Prevention of clinically manifest rheumatoid arthritis by B-cell directed therapy in the earliest phase of the disease (PRAIRI; “Prevention of RA by Rituximab”) study, patients with arthralgia without clinical arthritis were treated with rituximab, causing B cell depletion. Patients had to be positive for both ACPA and IgM-RF, but could not have experienced inflammatory arthritis nor received DMARDs in the past. Additional inclusion criteria were detectable CRP at screening with levels higher than 0.6 mg/L (the lower level of detection of high sensitivity CRP assay) or subclinical synovitis as detected either by ultrasound or MRI with gadolinium.
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