Comment on: Petri M, Madger LS. Comparison of Remission and Lupus Low Disease Activity State in Damage Prevention in a United States Systemic Lupus Erythematosus Cohort. Arthritis Rheum 2018; 1790– 1795
Commented by: Laurent Arnaud, Department of Rheumatology, National Reference Centre for Rare Systemic and Autoimmune Diseases East South-West (RESO), Strasbourg, France. Twitter: @Lupusreference. Email: Laurent.arnaud@chru-strasbourg.fr
Disease activity is defined as reversible manifestation. By contrast, damage is defined as irreversible manifestations that may result from the disease itself or side-effects of treatments. In systemic lupus erythematosus (SLE), disease activity has been shown to lead to long- term organ damage. Therefore, one aim of the Treat-to-target (T2T) strategy in SLE is to reach remission, or alternatively low disease activity when remission cannot be achieved [1]. The international DORIS collaboration [2] has proposed various definitions of remission (with or without abnormal serologic findings; with or without treatment). However, because prolonged complete remission is difficult to achieve in SLE [3], an alternative approach has been taken by Franklyn et al. [4], who developed and validated one definition for low disease activity: the lupus low disease activity state (LLDAS). In their paper, Petri & Madger used the Hopkins Lupus Cohort to study the association between time in remission and LLDAS and long-term organ damage in SLE. This is a very important question as it is crucial to confirm that LLDAS has an impact on damage and to determine for how long patients should be in those states to be protected against damage accrual.
For this, Petri & Madger analyzed data from 1,356 SLE patients in the Hopkins Lupus Cohort, followed up quarterly, with 77,105 person- months observed from 1987 to 2016. Three outcome measures were considered: clinical remission with or without treatment and LLDAS. Clinical remission without treatment was defined as a PGA <0.5 and a SLEDAI score of 0, with no prednisone or immunosuppressant use. Clinical remission on treatment was the same but allowed prednisone at ≤5 mg/day and maintenance treatment with immunosuppressants. LLDAS was defined as a SLEDAI score of ≤4 with no SLEDAI scores for the renal, central nervous system, serositis, vasculitis, and constitutional components, no increase in any SELENA SLEDAI composite index since the previous visit, a PGA of ≤1, and a prednisone dose of ≤7.5 mg/day. Immunosuppressants were allowed for LLDAS and hydroxychloroquine treatment was allowed for all 3 definitions.
Their results state that patients achieved clinical remission with or without treatment in only 13% and 27% of their follow-up visits, respectively. By contrast, patients achieved LLDAS in 50% of their follow- up months. Importantly, the rates of damage declined with increased percentage of prior time in either LLDAS or clinical remission on treatment. A major finding is that spending a short proportion of prior time (<25%) in clinical remission on treatment was associated with a relatively low rate of damage (rate ratio 0.54, P < 0.0001) compared to never achieving that condition while patients had to experience LLDAS at least 50% of the time to have a similar reduction in the rate of damage. For the months after a person had ≥2 previous damage events, even a small proportion of previous time in LLDAS was associated with a large reduction in damage risk.
In conclusion, LLDAS was an easier target to achieve than clinical remission on treatment in this large SLE cohort and both resulted in reduced risk of long-term damage. However, while a small percentage of time in clinical remission on treatment was associated with reduced damage, patients had to be in LLDAS at least 50% of the time to experience a similar reduction in the rate of damage (≈-50%). It is therefore easier to be “mediocre” than optimal (reaching LLDAS instead of remission) in SLE, but one has to be very good at being mediocre (at least 50% of the time in LLDAS state to reduce the risk of damage as effectively as remission).
References
- van Vollenhoven RF et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis. 2014 Jun;73(6):958-67
- van Vollenhoven RF et al. A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis. 2017 Mar;76(3):554-561
- Zen et al. Prolonged remission in Caucasian patients with SLE: prevalence and outcomes. Ann Rheum Dis. 2015 Dec;74(12):2117-22
- Franklyn et al. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis. 2016 Sep;75(9):1615-21.
