Validation of Disease Activity State Attainment as End Point in Systemic Lupus Erythematosus

Lupus low disease activity state (LLDAS) has been validated as an end point for clinical studies in patients with systemic lupus erythematosus (SLE), according to research results published in Lancet Rheumatology. Achievement of LLDAS has also been associated with significant protection against both disease flares and damage accrual.

Researchers conducted a prospective cohort study to examine the association between LLDAS and the development of irreversible end-organ damage and disease flares. Investigators recruited consecutive patients aged ≥18 years from 13 centers across 8 countries in the Asia-Pacific Lupus Collaboration. Longitudinal analysis included data from patients with ≥2 clinic visits throughout the study period.

Between May 2013 and December 2016, investigators recruited 1735 patients of whom 1707 patients (93% women; median age at diagnosis, 29 years [age range, 21-40 years]) were included in the final analysis. Researchers followed-up with patients for 2.2±0.9 years, for a total of 12,689 visits and a median visit interval of 0.28 years (interquartile range [IQR], 0.23-0.46 years). Median SLE Disease Activity Index 2000 (SLEDAI-2K) at enrollment was 4 (IQR, 2-6); 29.6% (n=506) of patients had SLEDAI-2K ≥6 at study entry. At baseline, 41.4% (n= 706) of patients had organ damage.

The definition of LLDAS was fulfilled by nearly 48% (n=6081) of patients, and 78% (n=1332) had ≥1 episode of LLDAS during the follow-up period. While the mean duration of LLDAS episodes was 0.3±0.2 years, 62.7% (n=1071) of patients achieved ≥1 episode of sustained LLDAS, defined as ≥2 consecutive visits in a state of LLDAS, with 48.2% (n=517) who sustained LLDAS for ≥12 months. Compared with patients who spent <50% of their observed time in LLDAS, those who spent ≥50% of their time in LLDAS had an overall lower SLEDAI-2K at baseline, a lower mean prednisolone dose during follow-up, and were significantly less likely to have ever had either vasculitis or renal disease.

Achievement of LLDAS was associated with a significant reduction in both flare and subsequent damage accrual at the following visit (hazard ratio [HR], 0.65 and 0.59; 95% CI, 0.56-0.75 and 0.45-0.76, respectively; P <.0001). Across the entire observation period, patients who spent ≥50% of the time in LLDAS had a significant reduction in both flare and damage accrual (HR, 0.41 and 0.54; 95% CI, 0.35-0.48 and 0.42-0.70, respectively; P <.0001). Researchers noted damage accrual in 31 (2.9%) of the 1071 patients with sustained LLDAS, compared with 113 (17.8%) of the 636 patients who never experienced sustained LLDAS (P <.0001). Sustained LLDAS ≥12 months was associated with a reduction in risk for subsequent damage (risk ratio, 0.14; 95% CI, 0.07-0.30; P <.0001)

Subgroup analyses indicated that achievement of LLDAS was less frequent in patients with active disease (SLEDAI-2K ≥6) at baseline, compared with patients with SLEDAI-2K ≤6 at baseline. Patients with active disease at baseline demonstrated a stronger association between LLDAS achievement and reduction in damage accrual, according to the results of a visit-by-visit analysis. An additional subgroup analysis that focused on patient ethnicity found that ethnicity had no role in the protective effect of LLDAS on damage accrual.

Among patients with existing damage at study baseline, investigators noted a significant reduction in the risk for further damage accrual if these patients were able to achieve LLDAS at any visit.

Study limitations included the observational nature of the research, the length of the follow-up period, and the results not being generalizable to patients who were not Asian.

“[T]his prospective multicenter study shows that LLDAS attainment is associated with reduction in flare and end-organ damage in SLE, thus validating it as an [endpoint] for clinical studies and development of treat-to-target strategies in SLE,” the researchers concluded.

Disclosures: This study was supported by AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Company, GlaxoSmithKline, Janssen Pharmaceuticals, Inc, and UCB Pharma, Inc. Please see the original reference for a full list of authors’ disclosures.

Reference

Golder V, Kandane-Rathnayake R, Huq M, et al; Asia-Pacific Lupus Collaboration. Lupus low disease activity state as treatment endpoint for systemic lupus erythematosus: a prospective validation study. Lancet Rheumatol. 2019;1(2):95-102.