HYDROXYCHLOROQUINE DOES NOT PREVENT THE FUTURE DEVELOPMENT OF RHEUMATOID ARTHRITIS IN A POPULATION WITH BASELINE HIGH LEVELS OF ANTIBODIES TO CITRULLINATED PROTEIN ANTIGENS AND ABSENCE OF INFLAMMATORY ARTHRITIS: INTERIM ANALYSIS OF THE STOPRA TRIAL
Authors: Kevin D Deane et al.
The StopRA trial is yet another ‘prevention trial’, aiming at inhibiting the development of rheumatoid arthritis (RA) and inflammatory arthritis (IA) in a high risk population of the disease. The authors enrolled 144 individuals with high levels of ACPAs (anti-CCP antibodies) and without signs of synovitis at baseline, and randomized them to either hydroxychloroquine (HCQ, 200-400 mg/day) or placebo (PBO) for 1 year and then followed them up for another two years. Over this period, 41 (35%) participants developed RA, 34% in the HCQ arm and 36% in the PBO arm (p=0.84).
The StopRA trial is an ambitious, publically funded and well-performed trial. Furthermore, the authors used a drug that many of us consider using in similar clinical situations, namely patients at high risk of developing an autoimmune condition, or in «pre-RA patients», – instead of an expensive bDMARD, unlikely to be approved in this situation in the near future. Unfortunately, the results suggest that individuals with high levels of ACPAs do not benefit from HCQ treatment and that HCQ does not prevent the development of RA over the next 3 years.
Overall, the various ‘preventive trials’ in pre-clinical RA suggest that it is difficult to halt the progression of the disease in the long-run and that we probably first need to better understand the natural history of the disease before attempting to prevent disease development with pharmaceutical interventions.