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

Eric F. Morand, Teodora Trasieva, Anna Berglind, Gabor G. Illei, Raj Tummala

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Abstract

Objectives In a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial (RCT) (MUSE [NCT01438489]) and then utilize LLDAS to discriminate between anifrolumab and placebo. Methods Patients received intravenous placebo (n=102) or anifrolumab (300 mg, n=99; 1,000 mg, n=104) Q4W plus standard of care for 48 weeks. LLDAS attainment (SLE Disease Activity Index 2000 ≤4 without major organ activity, no new disease activity, Physician's Global Assessment ≤1, prednisolone ≤7.5 mg/d and standard immunosuppressant dosage tolerance) was assessed. Associations with endpoints and LLDAS attainment differences between treatments were explored. Results LLDAS attainment at Week 52 was associated with SLE Responder Index 4 (SRI[4]) and British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) (74/85[87%] and 62/84[74%] were also SRI[4] and BICLA responders, respectively; both nominal p<0.001). Only 74/159 (47%) of SRI(4) and 62/121 (51%) of BICLA responders reached LLDAS. Anifrolumab-treated patients achieved earlier LLDAS, and more spent at least half their observed time in LLDAS (OR vs. placebo; 300 mg: 3.04, 95% CI 1.34 to 6.92, nominal p=0.008; 1,000 mg: 2.17, 95% CI 0.93 to 5.03, nominal p=0.072) vs placebo-treated patients. At Week 52, 17/102 (17%), 39/99 (39%) and 29/104 (28%) of patients on placebo, anifrolumab 300 and 1,000 mg, respectively, attained LLDAS (OR vs. placebo; 300 mg: 3.41, 95% CI 1.73 to 6.76, p<0.001; 1,000 mg: 2.03, 95% CI 1.01 to 4.07, nominal p=0.046). Conclusions LLDAS attainment represents a clinically meaningful SLE outcome measure, and anifrolumab is associated with more patients who met LLDAS criteria versus placebo. These data support LLDAS as an SLE RCT endpoint. Trial registration number NCT1438489; Post-results.

Original languageEnglish
Pages (from-to)706-713
Number of pages8
JournalAnnals of the Rheumatic Diseases
Volume77
Issue number5
DOIs
Publication statusPublished - 1 May 2018

Keywords

  • anifrolumab
  • low disease activity state
  • systemic lupus erythematosus
  • treat-to-target

Cite this

@article{e633bd0edc9143829d5f809bd58dac8f,
title = "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",
abstract = "Objectives In a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial (RCT) (MUSE [NCT01438489]) and then utilize LLDAS to discriminate between anifrolumab and placebo. Methods Patients received intravenous placebo (n=102) or anifrolumab (300 mg, n=99; 1,000 mg, n=104) Q4W plus standard of care for 48 weeks. LLDAS attainment (SLE Disease Activity Index 2000 ≤4 without major organ activity, no new disease activity, Physician's Global Assessment ≤1, prednisolone ≤7.5 mg/d and standard immunosuppressant dosage tolerance) was assessed. Associations with endpoints and LLDAS attainment differences between treatments were explored. Results LLDAS attainment at Week 52 was associated with SLE Responder Index 4 (SRI[4]) and British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) (74/85[87{\%}] and 62/84[74{\%}] were also SRI[4] and BICLA responders, respectively; both nominal p<0.001). Only 74/159 (47{\%}) of SRI(4) and 62/121 (51{\%}) of BICLA responders reached LLDAS. Anifrolumab-treated patients achieved earlier LLDAS, and more spent at least half their observed time in LLDAS (OR vs. placebo; 300 mg: 3.04, 95{\%} CI 1.34 to 6.92, nominal p=0.008; 1,000 mg: 2.17, 95{\%} CI 0.93 to 5.03, nominal p=0.072) vs placebo-treated patients. At Week 52, 17/102 (17{\%}), 39/99 (39{\%}) and 29/104 (28{\%}) of patients on placebo, anifrolumab 300 and 1,000 mg, respectively, attained LLDAS (OR vs. placebo; 300 mg: 3.41, 95{\%} CI 1.73 to 6.76, p<0.001; 1,000 mg: 2.03, 95{\%} CI 1.01 to 4.07, nominal p=0.046). Conclusions LLDAS attainment represents a clinically meaningful SLE outcome measure, and anifrolumab is associated with more patients who met LLDAS criteria versus placebo. These data support LLDAS as an SLE RCT endpoint. Trial registration number NCT1438489; Post-results.",
keywords = "anifrolumab, low disease activity state, systemic lupus erythematosus, treat-to-target",
author = "Morand, {Eric F.} and Teodora Trasieva and Anna Berglind and Illei, {Gabor G.} and Raj Tummala",
year = "2018",
month = "5",
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doi = "10.1136/annrheumdis-2017-212504",
language = "English",
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pages = "706--713",
journal = "Annals of the Rheumatic Diseases",
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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. / Morand, Eric F.; Trasieva, Teodora; Berglind, Anna; Illei, Gabor G.; Tummala, Raj.

In: Annals of the Rheumatic Diseases, Vol. 77, No. 5, 01.05.2018, p. 706-713.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial

T2 - Post-hoc analysis of the Phase IIb MUSE trial of anifrolumab

AU - Morand, Eric F.

AU - Trasieva, Teodora

AU - Berglind, Anna

AU - Illei, Gabor G.

AU - Tummala, Raj

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Objectives In a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial (RCT) (MUSE [NCT01438489]) and then utilize LLDAS to discriminate between anifrolumab and placebo. Methods Patients received intravenous placebo (n=102) or anifrolumab (300 mg, n=99; 1,000 mg, n=104) Q4W plus standard of care for 48 weeks. LLDAS attainment (SLE Disease Activity Index 2000 ≤4 without major organ activity, no new disease activity, Physician's Global Assessment ≤1, prednisolone ≤7.5 mg/d and standard immunosuppressant dosage tolerance) was assessed. Associations with endpoints and LLDAS attainment differences between treatments were explored. Results LLDAS attainment at Week 52 was associated with SLE Responder Index 4 (SRI[4]) and British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) (74/85[87%] and 62/84[74%] were also SRI[4] and BICLA responders, respectively; both nominal p<0.001). Only 74/159 (47%) of SRI(4) and 62/121 (51%) of BICLA responders reached LLDAS. Anifrolumab-treated patients achieved earlier LLDAS, and more spent at least half their observed time in LLDAS (OR vs. placebo; 300 mg: 3.04, 95% CI 1.34 to 6.92, nominal p=0.008; 1,000 mg: 2.17, 95% CI 0.93 to 5.03, nominal p=0.072) vs placebo-treated patients. At Week 52, 17/102 (17%), 39/99 (39%) and 29/104 (28%) of patients on placebo, anifrolumab 300 and 1,000 mg, respectively, attained LLDAS (OR vs. placebo; 300 mg: 3.41, 95% CI 1.73 to 6.76, p<0.001; 1,000 mg: 2.03, 95% CI 1.01 to 4.07, nominal p=0.046). Conclusions LLDAS attainment represents a clinically meaningful SLE outcome measure, and anifrolumab is associated with more patients who met LLDAS criteria versus placebo. These data support LLDAS as an SLE RCT endpoint. Trial registration number NCT1438489; Post-results.

AB - Objectives In a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial (RCT) (MUSE [NCT01438489]) and then utilize LLDAS to discriminate between anifrolumab and placebo. Methods Patients received intravenous placebo (n=102) or anifrolumab (300 mg, n=99; 1,000 mg, n=104) Q4W plus standard of care for 48 weeks. LLDAS attainment (SLE Disease Activity Index 2000 ≤4 without major organ activity, no new disease activity, Physician's Global Assessment ≤1, prednisolone ≤7.5 mg/d and standard immunosuppressant dosage tolerance) was assessed. Associations with endpoints and LLDAS attainment differences between treatments were explored. Results LLDAS attainment at Week 52 was associated with SLE Responder Index 4 (SRI[4]) and British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) (74/85[87%] and 62/84[74%] were also SRI[4] and BICLA responders, respectively; both nominal p<0.001). Only 74/159 (47%) of SRI(4) and 62/121 (51%) of BICLA responders reached LLDAS. Anifrolumab-treated patients achieved earlier LLDAS, and more spent at least half their observed time in LLDAS (OR vs. placebo; 300 mg: 3.04, 95% CI 1.34 to 6.92, nominal p=0.008; 1,000 mg: 2.17, 95% CI 0.93 to 5.03, nominal p=0.072) vs placebo-treated patients. At Week 52, 17/102 (17%), 39/99 (39%) and 29/104 (28%) of patients on placebo, anifrolumab 300 and 1,000 mg, respectively, attained LLDAS (OR vs. placebo; 300 mg: 3.41, 95% CI 1.73 to 6.76, p<0.001; 1,000 mg: 2.03, 95% CI 1.01 to 4.07, nominal p=0.046). Conclusions LLDAS attainment represents a clinically meaningful SLE outcome measure, and anifrolumab is associated with more patients who met LLDAS criteria versus placebo. These data support LLDAS as an SLE RCT endpoint. Trial registration number NCT1438489; Post-results.

KW - anifrolumab

KW - low disease activity state

KW - systemic lupus erythematosus

KW - treat-to-target

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U2 - 10.1136/annrheumdis-2017-212504

DO - 10.1136/annrheumdis-2017-212504

M3 - Article

VL - 77

SP - 706

EP - 713

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 5

ER -