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A summary of a prospective cohort study that compared the effects of attaining LLDAS in patients with newly diagnosed SLE versus established SLE

Sep 16, 2022
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Learning objective: After reading this article, learners will be able to describe the protective effects of using a lupus low disease activity state (LLDAS) as a treatment target in early onset SLE.

Systemic lupus erythematosus (SLE) is associated with a significant impact on health-related quality of life (HR-QoL) and until now there has been a lack of measures of treatment outcome status for use in clinical trials.1

Lupus low disease activity state (LLDAS), a measure that combines disease activity and treatment domains, is a prospectively validated treat-to-target strategy.1 Prospective and retrospective studies show that attainment of LLDAS is associated with better HR-QoL and offers a protective effect against flares, damage accrual, and mortality.1-3 However, these studies included only patients with established SLE, therefore, skewing the results and warranting investigation of the effects of LLDAS in patients with newly diagnosed SLE.

During the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, Eric Morand, Monash University, Melbourne, AU, presented the findings from a multicenter, prospective study comparing the effects of LLDAS attainment in patients with newly diagnosed versus established SLE.4 The key findings are summarized here.

Study design

This was a prospective, multicenter, cohort study conducted between May 2013 and December 2020 in patients aged ≥18 years and diagnosed with SLE using American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC) criteria. As shown in Figure 1, patients were divided into two cohorts: the inception cohort in which the patients were enrolled <1 year since the onset of SLE (n = 680) and the non-inception cohort in which the patients were enrolled >1 year since the onset of SLE (n = 3,426).

At 36 months, data were collected on:

  • Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score;
  • Physician Global Assessment (PGA) score;
  • medicine use, including prednisolone dose; and
  • clinical parameters.

The outcome measures included

  • flare assessment (at every visit);
  • damage accrual (yearly); and
  • HR-QoL (yearly).

Figure 1. The inception and non-inception cohorts over the 5-year follow-up* 

*Adapted from Morand.4

Results

Baseline characteristics

A total of 4,106 patients were included, with 680 and 3,426 patients in the inception and non-inception cohorts, respectively. Patients in the inception cohort were younger, showed more active disease, had higher prednisolone use, were less likely to be in LLDAS, and had less damage accrual at enrolment (Table 1). Only 13.6% of patients in the inception cohort accrued damage during a median follow-up of 2.2 years.

Table 1. Characteristics of the inception and non-inception cohorts*

Characteristic

Inception cohort
(n = 680)

Non-inception cohort
(n = 3,426)

p value

Median age, years (IQR)

33.0 (25.0–44.0)

40.0 (31.0–51.0)

<0.001

Median SLE duration at enrollment, years (IQR)

1.0 (0.0–1.0)

10.0 (5.0–16.0)

<0.001

Median study duration, years (IQR)

2.2 (0.9–3.7)

2.5 (1.0–5.4)

<0.001

PNL use ever, %

91.2

83.6

<0.001

Median TAM-PNL (IQR)

6.2 (3.2–10.3)

5.0 (2.2–8.6)

<0.001

Median AMS (TAM-SLEDAI-2K) (IQR)

3.1 (1.6–5.0)

2.8 (1.2–4.6)

0.002

Median TAM-PGA (IQR)

0.4 (0.3–0.8)

0.4 (0.2–0.7)

<0.001

Flare ever, %

57.5

52.2

0.012

Baseline organ damage, %

25.7

40.9

<0.001

Organ damage accrual, %

13.6

20.8

<0.001

LLDAS at baseline, %

28.7

50.5

<0.001

LLDAS ever (at least once), %

73.9

78.2

0.014

50% cumulative time in LLDAS, %

41.1

50.6

<0.001

3 months in sustained LLDAS, %

51.8

57.2

0.009

AMS, adjusted mean SLEDAI-2K; IQR, interquartile range; LLDAS, lupus low disease activity state; PNL, prednisolone; PGA, Physician Global Assessment; SLE, systemic lupus erythematosus; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; TAM, time-adjusted mean.
*Adapted from Morand.4

Lupus low disease activity state

At enrolment, significantly fewer patients were in LLDAS in the inception cohort compared with the non-inception cohort (28.7% vs 50.5%; p < 0.001). LLDAS was achieved at least once during follow-up by a lesser percentage of patients in the inception cohort compared with the non-inception cohort, at 73.9% and 78.2%, respectively. Limiting analysis only to patients who did not attain LLDAS at enrolment, time to first LLDAS attainment was significantly higher in the inception cohort compared with the non-inception cohort (hazard ratio, 1.60, 95% confidence interval, 1.401.82; p < 0.001).

Protective effect

A protective effect of LLDAS against flares was observed in both the inception and non-inception cohorts. In the inception cohort, in patients who had ever attained LLDAS, the protective effect against flares was statistically significant (p < 0.001). However, no significant association was observed for the protective effect against damage accrual in the inception cohort (p = 0.254) (Figure 2).

Figure 2. Protective effect of LLDAS against flares and damage accrual* 

LLDAS, lupus low disease activity state; LLDAS-50, LLDAS 50%.
*Data from Morand.4

Conclusion

This prospective cohort study demonstrated that time to first LLDAS attainment from baseline was shorter in the inception cohort, suggesting that LLDAS could be applied as a treat-to-target strategy at diagnosis in patients with newly diagnosed SLE. The attainment of LLDAS also showed a protective effect against flares in patients with recent onset of SLE (the inception cohort). However, there was no significant protection against damage accrual in this population mainly due to low rates of damage accrual in the first years after SLE diagnosis. Further long-term follow-up is therefore needed to establish if LLDAS offers a protective effect against damage accrual in patients with newly diagnosed SLE. Some other limitations of the study included variation in the definition of the inception cohort and change in disease activity in patients during the study period.

  1. Golder V, Kandane-RathnayakeR, Hoi AY, et al. Association of the lupus low disease activity state (LLDAS) with health-related quality of life in a multinational prospective study. Arthritis Res Ther. 2017;19:62.DOI: 1186/s13075-017-1256-6
  2. Golder V, Kandane-Rathnayake R, Huq M, et al. Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. Lancet Rheumatol. 2022;1(2):E95-E102. DOI: 1016/S2665-9913(19)30037-2
  3. Morand EF, Isenberg DA, Wallace DJ, et al. Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study,  2020;59(10):2930-2938. DOI: 10.1093/rheumatology/keaa029
  4. Morand E. Comparison of attainment and protective effects of the lupus low disease activity state in patients with newly diagnosed versus established SLE - A multicentre prospective study. Oral abstract #OP0142. European Alliance of Associations for Rheumatology 2022 Congress; Jun 2, 2022; Copenhagen, DK.