ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2012

Utility of the Lupus Low Disease Activity State Definition in Discriminating Responders in the Phase IIb Muse Trial of Anifrolumab in Systemic Lupus Erythematosus

E. Morand1, A. Berglind2, T. Sheytanova2, R. Tummala3 and G. Illei3, 1Monash University, Melbourne, Australia, 2AstraZeneca, Mölndal, Sweden, 3MedImmune, Gaithersburg, MD

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: , ,

Session Information

Date: Monday, November 14, 2016

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment III: Novel and Current Therapies

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Preliminary validation of a Lupus Low Disease Activity State (LLDAS) definition has demonstrated that LLDAS attainment is associated with reduced damage accrual in patients (pts) with SLE.1 However, it has not been evaluated in randomized controlled trials (RCTs). We present a post-hoc analysis evaluating LLDAS in the MUSE trial of anifrolumab in pts with moderate to severe SLE.2

Methods: LLDAS requires all of the following: SLEDAI–2K <4 without major organ activity, no new disease activity, Physician’s Global Assessment (0–3) <1, prednisolone <7.5 mg/day, and tolerance of standard immunosuppressant dosages.1 LLDAS criteria were assessed at each study visit. The utility of LLDAS, its association with other endpoints, and the difference in attaining LLDAS between pts treated with anifrolumab and placebo, were explored using descriptive statistics, logistic regression, and Gray’s test.

Results: During the 52-week study period of MUSE, pts received intravenous placebo (n=102), anifrolumab 300 mg (n=99), or anifrolumab 1,000 mg (n=104), in addition to standard of care, every 4 weeks for 48 weeks. LLDAS criteria were met, at least once, by 35%, 52%, and 46% of pts, respectively (odds ratio [OR] vs. placebo; 300 mg: 1.97, 90% CI 1.19, 3.25; p=0.027; 1,000 mg: 1.63, 90% CI 1.00, 2.68; p=0.103). Positive associations were observed between LLDAS and both the SLE Responder Index (SRI[4]) and BILAG-based Composite Lupus Assessment (BICLA) at 52 weeks, irrespective of treatment; 87% and 74% of pts meeting LLDAS criteria at 52 weeks also fulfilled the SRI(4) and BICLA criteria, respectively (χ2 = 57.61 and 55.18; p<0.0001 in each case). However, LLDAS was more stringent, with 47% of SRI(4) and 51% of BICLA responders reaching LLDAS.

Compared with placebo, anifrolumab 300 mg and 1,000 mg treatments were associated with increases in LLDAS attainment from Week 12 and Week 28, respectively, with ORs ranging between 1.7 and 3.6 (300 mg), and 1.7 and 2.5 (1,000 mg) at subsequent visits. At Week 52, LLDAS was achieved more frequently in the anifrolumab groups (OR vs. placebo; 300 mg: 3.41, 90% CI 1.93, 6.06, p=0.001; 1,000 mg: 2.03, 90% CI 1.13, 3.64, p=0.046). ORs for spending ≥50% of observed time in LLDAS were 3.04 (90% CI 1.53, 6.06; p=0.008) and 2.17 (90% CI 1.07, 4.39; p=0.072), respectively. Anifrolumab-treated pts reached LLDAS earlier than placebo pts (300 mg: χ2 = 6.39, p=0.012; 1,000 mg: χ2 = 2.44, p=0.119), Fig 1.

Conclusion: In the MUSE study, LLDAS correlated with clinically relevant definitions of treatment response and discriminated responders from non-responders. Treatment with anifrolumab 300 mg was associated with up to 3.6-fold increase in odds of LLDAS attainment. LLDAS should be considered as an outcome measure in SLE RCTs.

1Franklyn K, et al. Ann Rheum Dis 2015;doi:10.1136/annrheumdis-2015-207726.
2Furie R, et al. Arthritis Rheumtol 2015;67(Suppl 10):Abs 3223.

Disclosure: E. Morand, AstraZeneca, 2,Janssen Pharmaceutica Product, L.P., 2,UCB, 2,Abbvie, 9,UCB, 9; A. Berglind, AstraZeneca, 1,BMS, 1,AstraZeneca, 3; T. Sheytanova, AstraZeneca, 3; R. Tummala, AstraZeneca, 3; G. Illei, AstraZeneca, 1,Medimmune, 3.

To cite this abstract in AMA style:

Morand E, Berglind A, Sheytanova T, Tummala R, Illei G. Utility of the Lupus Low Disease Activity State Definition in Discriminating Responders in the Phase IIb Muse Trial of Anifrolumab in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/utility-of-the-lupus-low-disease-activity-state-definition-in-discriminating-responders-in-the-phase-iib-muse-trial-of-anifrolumab-in-systemic-lupus-erythematosus/. Accessed .

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