Date: Friday, November 6, 2020
Session Type: Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Treat-to-target (T2T) approaches to rheumatic disease require the definition and validation of low disease activity and remission endpoints that should be concentrically more stringent. The Lupus Low Disease Activity State (LLDAS) has been established as a low-disease activity endpoint for SLE, but multiple possible definitions for remission arise from the Definition of Remission in SLE (DORIS) framework. LLDAS and all remission definitions are associated with improved long term outcomes in terms of damage accrual and flare, but previous analyses suggested that Clinical Remission on Treatment (CROT) allowing 5mg/day prednisolone was insufficiently different from LLDAS (≤7.5 mg/day) to be used separately. Therefore, we examined a more stringent threshold, requiring daily prednisolone < 5mg (CROT< 5), a dose which requires physician and patient to change from standard 5 mg tablets.
Methods: Data from a prospective multinational cohort study of patients with SLE (ACR or SLICC criteria) undertaken in 17 centres between 2013-2017 were used. Time-dependent Cox proportional hazards models were used to compare LLDAS and DORIS definitions of remission in terms of impact on flares (SELENA flare index) and organ damage (SLICC damage index (SDI)). LLDAS and DORIS CROT were defined as described in Golder et al, 2019: CROT requires clinical SLEDAI-2K = 0 and physician global assessment (PGA) (0-3) < 0.5; CROT allows prednisolone ≤5 mg/day; whereas CROT< 5 excludes patients taking 5mg/day. LLDAS allows SLEDAI-2K ≤4 with no new/major organ activity, PGA ≤1, and prednisolone ≤7.5 mg.
18.659 visits of 2,384 patients collected over a mean (SD) 2.26 (1.34) years were analysed. LLDAS was attained in 8,883 (47.6%) visits, CROT in 6,521 (35.0%) and CROT< 5 in 4,373 (23.4%; mean (SD) daily prednisolone 1.16 (1.32) mg)), confirming that lowering the prednisolone threshold resulted in a more stringent remission definition compared to CROT. LLDAS was protective from flare and damage accrual whether assessed visit by visit or cumulatively using a 50% of time exposed threshold. Visit by visit analysis revealed that CROT< 5 was associated with slightly greater protection from future flare (HR (95% CI) 0.48 (0.42,0.54)) than CROT (HR 0.54 (0.49,0.60)). Similarly, future damage risk was slightly less with CROT< 5 (HR 0.60 (0.47,0.78)) than CROT (0.62 (0.50,0.78)). When measured cumulatively using a 50% of time exposed threshold, CROT < 5 was more protective from flare (HR 0.40 (0.35,0.46)) than CROT (0.45 (0.40,0.50)) but not from damage. The effect of cumulative LLDAS on damage accrual overtime remained significant after excluding patients in CROT< 5 (HR 0.74 (0.57,0.96), p=0.022) but not after excluding CROT. Cumulative LLDAS was independently associated with flare excluding either CROT or CROT< 5.
Conclusion: A remission definition requiring a ceiling dose of prednisolone less than 5 mg (CROT< 5) is more stringent than CROT (allowing 5 mg/day) and its effects are independent of LLDAS, while CROT is insufficiently distinct from LLDAS. Confirmation in other cohorts should be undertaken prior to agreeing on a definition of remission for SLE.
To cite this abstract in AMA style:Morand E, Golder V, Louthrenoo W, Luo S, Wu Y, Lateef A, Sockalingam S, Navarra S, Zamora L, Hamijoyo L, Katsumata Y, Harigai M, Chan M, O'Neill S, Goldblatt F, Chen Y, Hao Y, Zhang Z, Kikuchi J, Takeuchi T, Lau C, Li Z, Hoi A, Nikpour M, Kandane-Rathnayake R. Superior Discrimination Between LLDAS and DORIS Remission with Modification of Prednisolone Dose Threshold [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/superior-discrimination-between-lldas-and-doris-remission-with-modification-of-prednisolone-dose-threshold/. Accessed June 24, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/superior-discrimination-between-lldas-and-doris-remission-with-modification-of-prednisolone-dose-threshold/