60 CHAPTER 4 Abstract 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 atrisk 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.
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