@article{3000137,
    title = "Rheumatoid arthritis patients on persistent moderate disease activity on biologics have adverse 5-year outcome compared to persistent low-remission status and represent a heterogeneous group",
    author = "Genitsaridi, I. and Flouri, I. and Plexousakis, D. and Marias, K. and Boki, K. and Skopouli, F. and Drosos, A. and Bertsias, G. and Boumpas, D. and Sidiropoulos, P.",
    journal = "Arthritis Research and Therapy",
    year = "2020",
    volume = "22",
    number = "1",
    publisher = "BioMed Central Ltd.",
    doi = "10.1186/s13075-020-02313-w",
    keywords = "biological product;  disease modifying antirheumatic drug;  methotrexate;  prednisolone;  tumor necrosis factor inhibitor, adult;  adverse event;  adverse outcome;  age;  Article;  cohort analysis;  controlled study;  DAS28;  disease activity;  disease classification;  female;  follow up;  functional status;  Health Assessment Questionnaire;  human;  illness trajectory;  infection;  longitudinal study;  major clinical study;  male;  middle aged;  outcome assessment;  persistent higher moderate disease activity;  persistent lower moderate disease activity;  persistent moderate disease activity;  prognosis;  remission;  rheumatoid arthritis;  sex difference;  treatment duration",
    abstract = "Background: The long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity. Methods: We included longitudinally monitored RA patients from the Hellenic Registry of Biologic Therapies with persistent (cumulative time ≥ 50% of a 5-year period) moderate (pMDA, 3.2 < DAS28 ≤ 5.1) or remission/low (pRLDA, DAS28 ≤ 3.2) disease activity. The former was further classified into persistent lower-moderate (plMDA, DAS28 < 4.2) and higher-moderate (phMDA, DAS28 ≥ 4.2) subgroups. Five-year trajectories of functionality (HAQ) were the primary outcome in comparing pRLDA versus pMDA and assessing heterogeneity within the pMDA subgroups through multivariable mixed-effect regression. We further compared serious adverse events (SAEs) occurrence between the two groups. Results: We identified 295 patients with pMDA and 90 patients with pRLDA, the former group comprising of plMDA (n = 133, 45%) and phMDA (n = 162, 55%). pMDA was associated with worse 5-year functionality trajectory than pRLDA (+ 0.27 HAQ units, CI 95% + 0.22 to + 0.33; p < 0.0001), while the phMDA subgroup had worse 5-year functionality than plMDA (+ 0.26 HAQ units, CI 95% 0.18 to 0.36; p < 0.0001). Importantly, higher persistent disease activity was associated with more SAEs [pRLDA: 0.2 ± 0.48 vs pMDA: 0.5 ± 0.96, p = 0.006; plMDA: 0.32 ± 0.6 vs phMDA: 0.64 ± 1.16, p = 0.038]. Male gender (p = 0.017), lower baseline DAS28 (p < 0.001), HAQ improvement > 0.22 (p = 0.029), and lower average DAS28 during the first trimester since treatment initiation (p = 0.001) independently predicted grouping into pRLDA. Conclusions: In clinical practice, RA patients with pMDA while on bDMARDs have adverse long-term outcomes compared to lower disease activity status, while heterogeneity exists within the pMDA group in terms of 5-year functionality and SAEs. Targeted studies to better characterize pMDA subgroups are needed, in order to assist clinicians in tailoring treatments. © 2020 The Author(s)."
}