Prevention of rheumatoid arthritis: A systematic literature review of preventive strategies in at-risk individuals

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical peripheral polyarthritis in the hands and/or feet, leading to long-term disability if not treated effectively. RA is preceded by a preclinical phase, in which genetically predisposed individuals accumulate environmental risk factors, and during which autoimmunity develops, followed by the emergence of non-specific signs and symptoms before arthritis becomes manifest. Early treatment in at-risk individuals – i.e. before the disease is fully established – has the theoretical potential to delay or prevent disease onset, with a positive impact on both patients' life and society. Objectives: We aimed to understand the feasibility of preventive treatment in at-risk individuals, taking into account recently performed studies and ongoing clinical trials, as well as patient perspectives. Methods: We performed a systematic literature review (SLR) on Medline and Embase, searching articles published between 2010 and 2021 with the following key-words: “Rheumatoid arthritis”, “arthralgia”, “pre-treatment” or “prevent”. Results: Our SLR identified a total of 1821 articles. Articles were independently screened by two researchers. A total of 14 articles were included after screening, and an additional 8 reports were manually included. We identified ten relevant clinical trials performed in at-risk individuals, or in individuals with undifferentiated inflammatory arthritis. Although no treatment was shown to prevent RA onset, early treatment with rituximab and abatacept delayed onset of full-blown RA, and both conventional and biological disease-modifying anti-rheumatic drugs (DMARDs) decreased disease-related physical limitations and increased DAS28-defined remission, at least temporarily. Conclusions: This SLR demonstrates that early treatment of at-risk individuals may be effective in delaying RA onset, thereby decreasing disease-related limitations in individuals in the pre-clinical phase of RA. Whether this may ultimately lead to prevention of RA remains to be determined.