SLE-DAS as a disease activity measure: Post hoc analyses of phase II and III trials of anifrolumab

Accurate and practical disease activity measures in the management of systemic lupus erythematosus (SLE) are limited.¹ The SLE Disease Activity Score (SLE-DAS) is a recently validated 17-item tool that demonstrates high accuracy and sensitivity in assessing changes to disease activity.²

At the 14th European Lupus Meeting, Jesus presented post hoc analyses of phase II and III trials of anifrolumab to:

• derive and validate the cut-off value for SLE-DAS for defining severe disease activity (SDA);¹ and
• evaluate if SLE-DAS enables easy identification of patients with SDA and moderate-to-severe disease activity (MSDA), and with worse health-related quality of life (HR-QoL). ^1,2

Here, we summarize the key findings.

Methods^1,2

• These were post hoc analyses of aggregated intention-to-treat data from placebo arms in MUSE (NCT01438489), TULIP-1 (NCT02446912), and TULIP-2 (NCT02446899) trials on anifrolumab vs placebo in moderate-to-severe SLE.
• British Isles Lupus Assessment Group (BILAG-2004) Index, SLE Disease Activity Index 2000 (SLEDAI-2K), and the patient-reported outcomes ([PROs]: lupus quality of life, EuroQoL-5D, Functional Assessment of Chronic Illness Therapy – Fatigue, and Patient Global Assessment) were assessed. The SLE-DAS was retrospectively scored at each visit.
• The Mann-Whitney test was used to compare PROs between patients in SDA vs non-SDA and MSDA vs non-MSDA at Week 12 and Cohen’s d was used to compare the magnitude of these differences.

Key findings

SDA^1,2

• A total of 438 patients with SLE were included.
• At Week 12, 46.6% in the derivation cohort and 42.4% in the validation cohort were in SDA by BILAG-2004.
• SLE-DAS >9.90 (area under curve = 0.847) was the best cut-off to identify patients in SDA in the derivation cohort, which showed 77.8% sensitivity and 79.6% specificity in the validation cohort.
• Patients in SDA by SLE-DAS reported significantly worse impact in all HR-QoL PROs (Figure 1).

MSDA²

• Of 438 patients identified as MSDA by BILAG-2004, 96.1% were classified as MSDA by SLE-DAS, and 92.9% by SLEDAI-2K.
• At Week 12, SLE-DAS and SLEDAI-2K presented significantly worse impact in all HR-QoL PROs (Figure 1).

BILAG, British Isles Lupus Assessment Group; EQ-5D, EuroQoL-5D; FACIT-F, Functional Assessment of Chronic Illness Therapy – Fatigue; MSDA, Moderate-to-Severe Disease Activity; PtGA, Patient Global Assessment; QoL, quality of life; SDA, Severe Disease Activity; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; VAS, visual analog scale.
*Data from Jesus, et al.^1,2

 

Key learnings

SLE-DAS SDA and MSDA may be superior in identifying patients with worse HR-QoL, as compared with BILAG-2004 and SLEDAI-2K, thereby facilitating good physician-patient concordance. SLE-DAS could help identify patients with MSDA for SLE clinical trials and those who may require biologic therapy in clinical settings.