81 Prevention of rheumatoid arthritis Eighty-one patients were recruited in the study and randomized to receive 100 mg methylprednisolone followed by either a single infusion of 1000 mg rituximab (41 patients) or placebo (NaCl 0.9%; 40 patients). Patients were stratified for age (< 40 years old, or ≥ 40 years old) and sex before randomization, with a scheduled follow up of five years after the intervention. The primary outcome of the study was the time to development of clinical arthritis, defined as swollen and tender joints as observed by two independent investigators. Moreover, the study investigated circulating autoantibody levels and peripheral B and T cell numbers and subpopulation composition through fluorescence-activated cell sorting (FACS) analysis. Rituximab treatment was associated with a reduction of the baseline risk of developing RA at 12 months (55% reduction of risk compared to placebo group) and at 18 months (53% reduction of risk compared to placebo). Moreover, patients treated with a single infusion of rituximab had a delay of RA development of 12 months at the point when 25% of the subjects had developed arthritis (“25th percentile”). In contrast, at the end of follow-up time, the risk of RA development was not statistically significant different between treatment and placebo (34% after a median of 16.5 months vs. 40% after a median of 11.5 months, respectively). In summary, the PRAIRI study demonstrated that depletion of B cells in individuals with arthralgia significantly delayed RA onset, confirming that B lineage cells play an important role in disease pathogenesis, including progression to clinical overt RA [64]. Other strategies Statins Statins are lipid-lowering agents with a good safety profile and anti-inflammatory properties: in RA patients, statins improved disease activity scores and caused decreased inflammatory parameters [65]. Additionally, in mice models of RA, statins had a protective effect against disease development, and on a population level, statin use is associated with a reduced risk of developing RA [66,67]. Hence, statins were postulated to have a possible beneficial effect in preventing RA [68]. The STAtins to Prevent Rheumatoid Arthritis (STAPRA) trial investigated the ability of a statin to prevent development of RA in high risk individuals with arthralgia. Patients were required to have either high levels of ACPA (three times the ULN) or both ACPA and IgM-RF positivity without (a history of) arthritis, and were randomized to receive either 40 mg of atorvastatin or placebo daily for 3 years [69]. The primary outcome of the study was development of clinical arthritis, defined as one or more swollen joints out of 44 joints assessed (SJC44). A secondary outcome was the development of RA as defined by the ACR/EULAR 2010 classification criteria. The 4
RkJQdWJsaXNoZXIy MTk4NDMw