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Pragmatic targets for moderate/severe SLE and their implications for clinical care and trial design: sustained DORIS or LLDAS for at least 6 months is sufficient while their attainment for at least 24 months ensures high specificity for damage-free progression

Pitsigavdaki S, Nikoloudaki M, Garantziotis P, Silvagni E, Repa A, Marangoni A, Flouri I, Avgoustidis N, Parperis K, Fanouriakis A, Govoni M, Sidiropoulos P, Boumpas DT, Bortoluzzi A, Bertsias G (2024)

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Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 83

Pages Range: 464-474

Journal Issue: 4

DOI: 10.1136/ard-2023-224919

Abstract

Objectives Treatment targets in systemic lupus erythematosus (SLE) have been validated in unselected—in terms of severity—cohorts, which limits their generalisability. We assessed remission (Definition of Remission in SLE (DORIS)) and Lupus Low Disease Activity State (LLDAS) in a historical cohort of 348 patients with active moderate-to-severe disease and median follow-up of 5 years. Methods Active SLE was defined as Physician Global Assessment ≥1.5 and/or SLE Disease Activity Index 2000 ≥6, requiring therapy intensification. DORIS/LLDAS, organ damage, flares and adverse events were monitored. Shared frailty survival, generalised linear models and K-means clustering were applied. Results Sustained DORIS and LLDAS for ≥6 months occurred in 41.1% and 80.4%, respectively, and resulted in reduced damage accrual (HR: 0.58; 95% CI 0.36 to 0.93 and 0.61; 0.43 to 0.86) and severe flares (HR: 0.14; 0.08 to 0.27 and 0.19; 0.13 to 0.27). LLDAS without DORIS was also protective (HR: 0.65; 0.43 to 0.98 for damage, 0.49; 0.36 to 0.67 for flares). Models fitting increasing duration of targets showed that DORIS ≥50% and LLDAS ≥60% of time, or alternatively, ≥24 and ≥36 months, achieved optimal balance between feasibility (20.2–41.7%) and specificity (73.3–86.1%) for damage-free outcome. These targets were linked to reduced serious adverse events (risk ratio (RR): 0.56–0.71), hospitalisation (RR: 0.70) and mortality (RR: 0.06–0.13). Patients with predominant arthritis and mucocutaneous disease experienced reduced DORIS/LLDAS, compared with counterparts with major organ involvement. Conventional drugs were more frequently used in the former group, whereas potent immunosuppressive/biological agents in the latter. Conclusions In moderate-to-severe SLE, sustained DORIS/ LLDAS for at least 6 months is sufficient, while attainment for at least 24 months ensures higher specificity for damage-free progression, thus facilitating treat-to-target strategies and clinical trials. Arthritis and skin disease represent unmet therapeutic needs that could benefit from novel biologics.

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How to cite

APA:

Pitsigavdaki, S., Nikoloudaki, M., Garantziotis, P., Silvagni, E., Repa, A., Marangoni, A.,... Bertsias, G. (2024). Pragmatic targets for moderate/severe SLE and their implications for clinical care and trial design: sustained DORIS or LLDAS for at least 6 months is sufficient while their attainment for at least 24 months ensures high specificity for damage-free progression. Annals of the Rheumatic Diseases, 83(4), 464-474. https://doi.org/10.1136/ard-2023-224919

MLA:

Pitsigavdaki, Sofia, et al. "Pragmatic targets for moderate/severe SLE and their implications for clinical care and trial design: sustained DORIS or LLDAS for at least 6 months is sufficient while their attainment for at least 24 months ensures high specificity for damage-free progression." Annals of the Rheumatic Diseases 83.4 (2024): 464-474.

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