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
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:83 |
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| Enthalten in: |
Annals of the rheumatic diseases - 83(2024), 4 vom: 12. März, Seite 464-474 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pitsigavdaki, Sofia [VerfasserIn] |
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| Links: |
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| Themen: |
Immunosuppressive Agents |
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| Anmerkungen: |
Date Completed 14.03.2024 Date Revised 24.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1136/ard-2023-224919 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM367236141 |
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| 245 | 1 | 0 | |a Pragmatic targets for moderate/severe SLE and their implications for clinical care and trial design |b 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 |
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| 500 | |a Date Completed 14.03.2024 | ||
| 500 | |a Date Revised 24.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Lupus Erythematosus, Systemic | |
| 650 | 4 | |a Outcome Assessment, Health Care | |
| 650 | 4 | |a Therapeutics | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 700 | 1 | |a Nikoloudaki, Myrto |e verfasserin |4 aut | |
| 700 | 1 | |a Garantziotis, Panagiotis |e verfasserin |4 aut | |
| 700 | 1 | |a Silvagni, Ettore |e verfasserin |4 aut | |
| 700 | 1 | |a Repa, Argyro |e verfasserin |4 aut | |
| 700 | 1 | |a Marangoni, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Flouri, Irini |e verfasserin |4 aut | |
| 700 | 1 | |a Avgoustidis, Nestor |e verfasserin |4 aut | |
| 700 | 1 | |a Parperis, Konstantinos |e verfasserin |4 aut | |
| 700 | 1 | |a Fanouriakis, Antonis |e verfasserin |4 aut | |
| 700 | 1 | |a Govoni, Marcello |e verfasserin |4 aut | |
| 700 | 1 | |a Sidiropoulos, Prodromos |e verfasserin |4 aut | |
| 700 | 1 | |a Boumpas, Dimitrios T |e verfasserin |4 aut | |
| 700 | 1 | |a Bortoluzzi, Alessandra |e verfasserin |4 aut | |
| 700 | 1 | |a Bertsias, George |e verfasserin |4 aut | |
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