Low Disease Activity Early in the Course of Systemic Lupus Erythematosus

In patients with systemic lupus erythematosus (SLE), remission and low disease activity (LDA) have been shown to be protective of damage accrual, mortality, and flares; they have also been shown to be associated with a better health-related quality of life.¹ However, the large majority of published studies include patients with long-standing disease. Nevertheless, a previous study has shown that achieving Lupus LDA State (LLDAS) early in the course of the disease (6 months) is protective of damage accrual.² Further, remission is less likely to be attained in non-White populations, at least early in the course of the disease.³ Therefore, more information is needed to evaluate the probability of achieving LLDAS early in the course of the disease and the impact of achieving it. In this issue of The Journal of Rheumatology, Golder et al show the different protective effects of LLDAS in patients with SLE with newly diagnosed vs those with established disease.⁴

Current approaches for the management of SLE suggest that patients should achieve remission as promptly as possible; if that is not achieved, LLDAS should be the alternative outcome.^5,6 Unfortunately, remission has been achieved in less than 50% of the time in several cohorts worldwide,^7-12 with the exception of some European cohorts in which higher rates of achieving remission have been reported.^13,14 Further, the Systemic Lupus International Collaborating Clinics (SLICC) cohort has shown that achieving either remission or LDA independently prevents the occurrence of damage accrual. It should be noted, however, that in the SLICC study, remission was more likely to prevent damage in some specific domains including ophthalmologic, cardiovascular, and renal, although the number of events in these domains was relatively low.¹⁰

In the Hopkins Lupus cohort, African American ethnicity was associated with a lower probability of achieving remission and LLDAS,^3,15 suggesting that we need to have better management approaches for non-White populations. Perhaps for the time being, and until new treatments are available, we could accept LLDAS as a more realistic outcome for some patients with SLE.

Thus, it is important to find out whether LLDAS is achievable early in the course of the disease and whether it is good enough for some patient groups. In this context, the Asia Pacific Lupus Collaboration (APLC) study⁴ in this issue of The Journal has shown that LLDAS is achievable over the course of the disease. In fact, at enrollment, 29.6% of the patients with less than 12 months of disease duration (the inception cohort) were on LLDAS vs 52.3% of the patients in the noninception cohort. During the follow-up, however, these percentages increased to 74% and 79.4%, reflecting an increase of 44.4% and 27.1%, respectively.⁴ Of note, patients who were not in LLDAS at baseline could have had a more severe/refractory disease; this could be particularly true for patients in the noninception cohort.

In the entire cohort, APLC has shown that LLDAS prevented damage accrual. However, in the inception cohort, such protective effect could not be demonstrated, which probably relates to the relatively small number of events.⁴ The protective effect of LLDAS on damage accrual early in the course of the disease has been previously shown in an Italian cohort.² In patients who were not able to achieve LLDAS in the first 6 months, the odds ratio for the risk of damage accrual was 5.0 (95% CI 1.5-16.6).

Additionally, the APLC cohort has shown that LLDAS prevented flares in both the inception and the noninception cohorts. This was particularly true for those who achieved LLDAS in the first 6 months: flares at 12 months occurred in 39% of the patients who achieved LLDAS vs 60% for those who did not achieve it.⁴ The association between LDA and flares is consistent with the data from the Toronto Lupus Cohort.¹⁶ Flares have shown to be predictive of damage accrual¹⁷; therefore, the effect of lower occurrence of flares is quite relevant for all patients with SLE.

A treat-to-target strategy has been proposed for SLE: Even though there is consensus that remission is the ideal treatment target, the more realistic target is LLDAS.¹⁸ Therefore, we need more information about the impact of achieving these targets, particularly early in the course of the disease. In that sense, the work presented by Golder et al⁴ is quite relevant at the present time.

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