Beyond Disease Activity: Fatigue and Health-Related Quality of Life in Rheumatoid Arthritis Remission and Low Disease...

Background/Objectives: Remission and low disease activity (LDA) are established treatment targets in rheumatoid arthritis (RA), but they may not imply normalization of patient-perceived disease burden. Fatigue and health-related quality of life (HRQoL) provide complementary measures of patient-perceived health beyond inflammatory disease activity. Moreover, disease activity states defined by the Disease Activity Score in 28 joints (DAS28) and the Routine Assessment of Patient Index Data 3 (RAPID3) may be associated with different patient-reported outcome profiles. We aimed to compare fatigue and HRQoL in patients with RA classified as being in remission or LDA with those of controls and to assess agreement between DAS28 and RAPID3 classifications. Methods: We conducted a cross-sectional comparative study with a control group within the BELL-RA-LIFE cohort including 275 patients with RA aged >50 years and 300 controls with a comparable age and sex distribution. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and HRQoL using the Short Form-12 Physical (PCS) and Mental Component Summary (MCS) scores. Patients were classified independently according to DAS28 and RAPID3. Multivariable linear regression models adjusted for age, sex, body mass index, and hemoglobin were used to estimate differences versus controls. Agreement between DAS28 and RAPID3 was assessed using weighted Cohen's kappa. Results: No statistically significant differences from controls were detected in FACIT-F or MCS scores among patients in DAS28 remission, although PCS scores were lower (adjusted difference -3.37, 95% CI -5.56 to -1.18; nominal p = 0.003; Holm-adjusted p = 0.033). DAS28-defined LDA was associated with greater fatigue and poorer PCS scores, although these differences did not remain statistically significant after Holm adjustment (adjusted p = 0.256 and p = 0.100, respectively), whereas MCS scores remained significantly lower (adjusted difference -5.15, 95% CI -8.14 to -2.15; nominal p = 0.001; adjusted p = 0.012). In patients in RAPID3 remission, PCS and MCS scores did not differ significantly from controls, while FACIT-F scores were higher; this difference did not remain statistically significant after Holm adjustment (adjusted p = 0.117); no statistically significant differences were detected for RAPID3-defined LDA across the three outcomes. Overall agreement between DAS28 and RAPID3 was limited (quadratic weighted κ = 0.35, 95% CI 0.26-0.44), with no significant difference between women and men (κ = 0.30 and 0.41, respectively; Δκ = 0.11, 95% CI -0.12 to 0.31; p = 0.34). RAPID3 more frequently classified patients into higher disease activity categories than DAS28 in 80.6% of discordant classifications. Conclusions: Remission and LDA in RA were associated with different residual health burdens when assessed using DAS28. Patients in DAS28 remission had significantly lower physical HRQoL than controls, while those in DAS28-defined LDA had significantly poorer mental HRQoL. No statistically significant differences in fatigue or HRQoL were observed for RAPID3-defined remission or LDA. Agreement between DAS28 and RAPID3 was limited and directional, with RAPID3 more frequently assigning patients to higher disease activity categories. These findings support the complementary assessment of inflammatory disease activity and patient-reported health in patients with RA.