Lupus Low Disease Activity State in patients with recent onset vs established SLE

Lupus low disease activity state (LLDAS) is a validated treat-to-target goal in systemic lupus erythematosus (SLE). However, data on protective associations of LLDAS in newly diagnosed patients to those with established disease is scarce.

Golder et al. recently published an article in The Journal of Rheumatology, comparing attainment and protective effects of LLDAS between inception and non-inception cohort patients from a large multinational prospective longitudinal study. Here, we provide a summary of their findings and an expert opinion by one of the authors, Mandana Nikpour.

Methods¹

• Patients with SLE from a 13-country longitudinal SLE cohort between 2013 and 2020 were studied prospectively.
• Patients with disease duration <1 year at enrolment were categorized as inception (newly diagnosed) cohort.
• Primary outcomes assessed were organ damage accrual and occurrence of flare episodes.
• Patient characteristics between inception and non-inception cohorts were compared.
• Cox regression analyses were performed to examine the association of:
  • first LLDAS attainment in patients who were not in LLDAS at enrolment; and
  • LLDAS attainment with damage accrual and flare at a subsequent visit.

Key findings¹

Patient characteristics

• A total of 4,100 patients were studied.
  • Median age was 29 years at SLE diagnosis and 92% were female.
  • Median study duration was 2.5 years.
• The inception cohort (16% of patients) was younger, and had higher disease activity and medication usage including high-dose glucocorticoids, but had less organ damage at enrolment compared with the non-inception cohort.
  • Fewer inception cohort patients were in LLDAS at enrolment than the non-inception cohort (29.6% vs 52.3%; p<0.001), yet three-quarters of both cohorts attained LLDAS at least once during follow-up.

Time to first LLDAS attainment

• Among patients not in LLDAS at enrolment, inception cohort patients attained LLDAS significantly faster and were about 60% more likely to achieve LLDAS than non-inception cohort patients (hazard ratio = 1.60; p < 0.0001).

LLDAS attainment and organ damage accrual

• Unlike the inception cohort, a statistically significant negative association between LLDAS attainment and organ damage accrual was observed in the non-inception cohort.

LLDAS attainment and flare

• Attaining LLDAS significantly reduced the risk of flare at subsequent visits in both the inception and non-inception cohorts.
• Compared with patients not attaining LLDAS, inception cohort patients attaining LLDAS by 6 months were significantly less likely to have flares by 12 and 24 months after enrolment (Figure 1).

DA, damage accrual; LLDAS, Lupus Low Disease Activity State. 
*Data from Golder, et al.¹ Created with BioRender.com.
^†p = 0.0011.
^‡p = 0.0023.

 

Key learnings

Consistent with the natural history of SLE, newly diagnosed patients had higher disease activity, more flares, and received more treatment. Nevertheless, these patients attained LLDAS faster than those with established SLE and experienced fewer flares when attaining LLDAS within 6 months. LLDAS attainment was also protective against damage accrual and flare in patients with established disease. These findings endorse attaining LLDAS as a clinical treatment target in both newly diagnosed and established SLE.

Question for expert