POS0479 THE IMPACT OF FLARES ON PATIENT REPORTED OUTCOMES IN RHEUMATOID AND UNDIFFERENTIATED ARTHRITIS PATIENTS – A SUB-ANALYSIS OF THE IMPROVED STUDY
Authors: J. M. Maassen, S. A. Bergstra, P. D. de Buck, M. van Oosterhout, T. Huizinga, C. Allaart
Journal: Annals of the Rheumatic Diseases (2021)

Background: In rheumatoid arthritis (RA) patients in low disease activity, flares are associated with symptom deterioration. Patients in clinical remission may flare but still have low disease activity. How does this affect patient reported outcomes? Objectives: To evaluate the prevalence of disease flares in patients treated to target drug free remission, and to study the impact of disease flares on patient-reported outcomes (PROs) for flares with different impact on disease activity. Methods: In the IMPROVED study 610 patients with rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated to target drug free remission (DAS &lt;1.6) for 5 years. As soon as DAS was &lt;1.6, treatment was tapered to discontinuation. Patients with at least 8 months follow-up were selected. A flare was defined according to three definitions; A ) DAS ≥1.6 and ≥0.6 increase from the previous visit regardless of the previous DAS; B ) minor flare from remission; a DAS ≥1.6 with &lt;0.6 increase and previous DAS &lt;1.6; C ) major flare from remission; a DAS ≥1.6 with ≥0.6 increase and previous DAS &lt;1.6. Linear mixed models were used to compare functional ability, measured by the health assessment questionnaire (HAQ), at visits where a flare occurred versus visits without a flare. Fisher’s exact test were used to compare percentages with ≥0.22 HAQ increases between groups with and without LDA at the moment of flare. A generalized linear mixed model was used to calculate the odds ratio for a deterioration of ≥20 mm in VAS of PROs global health (GH), disease activity, pain and morning stiffness (from the preceding visit) during a flare. Results: Of the 585 patients with sufficient follow-up, 75% experienced a flare A , 26% a flare B , and 68% a flare C , at least once. Most flares were observed after t=8 and t=12 months. In 55%, 100%, and 69% of visits with a flare A, B or C, the patients were still in LDA (DAS=&lt;2.4). In 55% of the visits where a flare was associated with a DAS increase ≥0.6 (flare A &amp; C) there was also clinically relevant increase in HAQ of ≥0.22. The mean difference in HAQ was 0.27 with flare A (p&lt;0.01), 0.03 with flare B (p=0.72) and 0.18 with flare C (p&lt;0.01). If was DAS &gt;2.4 (LDA) at the moment of flare, HAQ increased ≥0.22 in 68% of all flares A, and 77% of all flares C (p-values &lt;0.01, compared to flares where patients were still in LDA, DAS=&lt;2.4). The odds ratios of a &gt;20 mm deterioration in VAS global health, VAS disease activity, VAS pain and VAS morning stiffness was significant ≥1 for flares with a ≥0.6 increase in DAS (flares A and C), and ≤1 for minor flares (B) (table 1). Conclusion: In early arthritis patients, during 5 years treated to target drug free DAS-remission, disease flares with loss of DAS-remission were common. Although the majority of patients who flared were still in LDA, most reported more pain, morning stiffness, increased disease activity and a diminished global health. On average, deterioration in HAQ only exceeded the minimum clinically important difference (delta HAQ &gt;=0.22) in case of a ≥0.6 increase in DAS, independent of the previous DAS. Depending on the definition of flare, up to 45% of patients lost DAS LDA, and in this group the functional deterioration significantly more often exceeded the MCID as compared to the patients that flared but were still in LDA. More research is needed to find out which patients are most at risk for clinically relevant flares, and to evaluate the impact of flares in patients with remission on long term outcomes. Table 1. Odds Ratios and 95% confidence intervals for &gt; 20 mm increase in PROs on 100mm visual analogue scales Flare A Flare B (minor ) Flare C (major ) Prevalence ≥20 mm a OR (95% CI) Prevalence ≥20 mm a OR (95% CI) Prevalence ≥20 mm a OR (95% CI) Global health 62% 2.1 (1.5; 2.8) 45% 0.5 (0.4; 0.7) 62% 1.4 (1.1; 1.8) Disease activity 62% 2.5 (1.7; 3.8) 45% 0.4 (0.3; 0.6) 62% 2.1 (1.4; 3.0) Pain 87% 2.0 (1.3; 3.1) 78% 0.5 (0.3; 0.8) 87% 1.8 (1.2; 2.5) Morning stiffness 84% 1.7 (1.1; 2.6) 77% 0.6 (0.4; 0.9) 86% 2.1 (1.5; 2.9) a The prevalence of &gt;20 mm deterioration in VAS PRO’s during a visit with a flare. Acknowledgements: We would like to thank all patients for their contribution as well as the rheumatologists who participated in the IMPROVED-study group. We would also like to thank all other rheumatologists and trainee rheumatologists who enrolled patients in these studies, and all research nurses for their contributions. Disclosure of Interests: Johanna M. Maassen: None declared, Sytske Anne Bergstra: None declared, Petronella DM de Buck: None declared, M. van Oosterhout: None declared, Thomas Huizinga: None declared, Cornelia Allaart Grant/research support from: the IMPROVED study was designed by the investigators and financially supported by AbbVie in the first year.