ABSTRACT
BACKGROUND: Rheumatoid arthritis (RA) is characterized by intermittent flares of disease activity with a significant impact on patients' lives. However, distinguishing flare from daily symptom variation may be approached differently by patients and healthcare providers, potentially hampering shared decision-making when treating RA. OBJECTIVES: To provide a comprehensive overview of RA flare definitions reported in the published literature, and to compare these with patients' perceptions of the flare concept according to qualitative evidence. METHODS: A systematic search was conducted on August 30th, 2022, and updated on September 30th, 2023, for both quantitative and qualitative studies reporting "flare" or related terms in the context of RA. We searched the following databases: Pubmed, EMBASE, Web of Science, Cochrane Library, and CINAHL. Definitions of RA flare reported in quantitative studies were summarized descriptively. In parallel, a thematic synthesis of qualitative studies was performed to outline patients' views on the concept of flare, and to compare these with the currently used definitions. RESULTS: Among 32,864 potentially eligible records, 304 studies were included, 5 of which used qualitative/mixed methods to study patients' perceptions of flare. Remarkably, 62 different definitions for RA flare were reported, with many studies reporting more than one. The most commonly used definitions (54 %) were based on disease activity indices, with DAS28-based definitions the most widely applied (84 %). For each of the disease activity indices, several different cutoffs to define flares were used. Various definitions based on physician report were applied in 24 % of cases, while patient-reported criteria represented only 15 % of the applied definitions. Thematic synthesis of the qualitative/mixed-methods studies highlighted the multidimensional impact of flares on patients' lives, resulting in five sequential overarching themes: "Living with RA: a balancing act", "Flare: a disturbance of this balance", "The biopsychosocial impact of flares", "Self-management: the first line of defense", and "Medical help: the last resort". In turn, these five themes were underpinned by a central theme of "Uncertainty and variability". CONCLUSION: We found a striking heterogeneity regarding the conceptualization and measurement of RA flare in the published literature. Although qualitative evidence highlighted the considerable impact of flares on patients' wellbeing, the majority of reported flare definitions were not based on patient report. There is a need to bridge this gap by aligning patients' and healthcare professionals' views on what distinguishes a flare from acceptable symptom variability when living with RA.