Examining Lupus Low Disease Activity State as an SLE Outcome Measure

Lupus low disease activity state (LLDAS) attainment in patients with systemic lupus erythematosus (SLE) is a clinically meaningful disease outcome measure, according to results of the MUSE trial (ClinicalTrials.gov identifier: NCT01438489) published in Annals of the Rheumatic Diseases.¹ In addition, anifrolumab was associated with more patients meeting LLDAS vs placebo.

The MUSE trial was a post hoc analysis of the phase 2b, randomized controlled study including 305 patients aged 18 to 65 years with moderate to severe SLE. Participants were randomly assigned to receive intravenous placebo (n=102), anifrolumab 300 mg (n=99), or anifrolumab 1000 mg (n=104) every 4 weeks for 48 weeks, plus standard therapy. LLDAS was conceptually defined as a “state which, if sustained, is associated with a low likelihood of adverse outcome, considering disease activity and medication safety.”²

LLDAS attainment was evaluated based on SLE Disease Activity Index 2000 ≤4 without major organ activity, no new disease activity, Physician’s Global Assessment ≤1, prednisolone ≤7.5 mg per day, and standard immunosuppressant dosage tolerance. Researchers examined the associations with endpoints and LLDAS achievement differences between treatment groups.

Study results demonstrated that LLDAS was attained by 16.7% of participants at 24 weeks. Moreover, at 24 weeks, 80.4% of patients who attained LLDAS achieved the primary endpoint of SLE Responder Index 4 (SRI4) with oral corticosteroid taper. At  52 weeks, 27.9% of patients achieved LLDAS compared with 52.1% and 40.2% of participants attaining SRI4 or British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA), respectively. Although 87.1% (74 of 85) of the LLDAS responders were SRI4 responders, only 46.5% (74 of 159) of SRI4 responders attained LLDAS (P <.001).

In addition, although 73.8% of LLDAS responders met BICLA criteria, only 51.2% of BICLA responders achieved LLDAS (P <.001). Anifrolumab-treated participants, compared with placebo-treated patients, attained earlier LLDAS and spent at least half of their observed time in LLDAS (odds ratio [OR] with anifrolumab 300 mg, 3.04; 95% CI, 1.34-6.92; P =.008; and OR with anifrolumab 1000 mg, 2.17; 95% CI, 0.93-5.03; P =.072).

At 52 weeks, 17%, 39%, and 28% of patients receiving placebo, anifrolumab 300 mg, and anifrolumab 1000 mg, respectively, attained LLDAS (OR with anifrolumab 300 mg, 3.41; 95% CI, 1.73-6.76; P <.001; and OR with anifrolumab 1000 mg, 2.03; 95% CI, 1.01-4.07; P =.046).

The investigators concluded that achievement of LLDAS is a clinically meaningful outcome measure of SLE disease activity. Treatment with anifrolumab is superior to placebo with respect to LLDAS attainment and persistence in patients with active SLE. They suggest that LLDAS should be used as a measure of response in clinical trials exploring new therapies for patients with SLE.

References

1. Morand EF, Trasieva T, Berglind A, Illei GG, Tummala R. Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hoc analysis of the Phase IIb MUSE trial of anifrolumab [published online February 2, 2018]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2017-212504.
2. Franklyn K, Lau CS, Navarra SV, et al; Asia-Pacific Lupus Collaboration. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis. 2016;75(9):1615-1621.