Pharmacokinetics, pharmacodynamics, and safety of subcutaneous anifrolumab in patients with systemic lupus erythematosus, active skin disease, and high type I interferon gene signature: a multicentre, randomised, double-blind, placebo-controlled, phase 2 study

IntroductionThe Systemic Lupus Erythematosus (SLE) Prospective Observational Cohort Study (SPOCS) aims to describe the disease course of SLE and its association with type I interferon gene signature (IFNGS) status.Methods and analysisSPOCS is an international, multicentre, prospective, observational cohort study designed to follow patients through biannual study visits during a 3-year observation period. Patients ≥18 years old with a physician diagnosis that meets the American College of Rheumatology or Systemic Lupus International Collaborating Clinics SLE classification criteria will be included. SPOCS will comprehensively analyse clinical features, disease progression and treatment, SLE outcomes, health status assessments and quality of life, and healthcare resource utilisation of patients with moderate to severe SLE. A four-gene test will be used to measure IFNGS status; scores will be compared with a pre-established cut-off. Patients will be stratified by low or high IFNGS expression levels. Enrolment began in June 2017, and study completion is expected in 2022. The total number of anticipated patients was initially planned for 1500 patients and was amended to 900 patients owing to slow accrual of eligible patients.Ethics and disseminationThe ethics committee/institutional review board/independent ethics committee at each study site approved the SPOCS protocol prior to study initiation (protocol number: D3461R00001, version 3.0, 26 June 2019). Study findings will be disseminated through peer-reviewed publications and presentations at scientific meetings.Trial registration numberNCT03189875.

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185 Baricitinib-associated changes in type I interferon gene signature during a 24-week phase 2 clinical SLE trial

10.1136/lupus-2019-lsm.185 ◽

2019 ◽

Cited By ~ 2

Author(s):

Thomas Dörner ◽

Yoshiya Tanaka ◽

Michelle Petri ◽

Josef S Smolen ◽

Ernst R Dow ◽

...

Keyword(s):

Type I Interferon ◽

Gene Signature ◽

Type I ◽

Phase 2 ◽

Interferon Gene

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AB0167 Pharmacokinetics of Sifalimumab and Target Modulation of a Type I Interferon Gene Signature in Patients with Moderate to Severe Systemic Lupus Erythematosus

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-eular.4529 ◽

2015 ◽

Vol 74 (Suppl 2) ◽

pp. 946.2-946 ◽

Cited By ~ 1

Author(s):

C. Morehouse ◽

P. Brohawn ◽

B. Higgs ◽

B. Zheng ◽

Y. Yao ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Type I Interferon ◽

Gene Signature ◽

Type I ◽

Systemic Lupus ◽

Severe Systemic Lupus Erythematosus ◽

Interferon Gene

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Anifrolumab effects on rash and arthritis: impact of the type I interferon gene signature in the phase IIb MUSE study in patients with systemic lupus erythematosus

Lupus Science & Medicine ◽

10.1136/lupus-2018-000284 ◽

2018 ◽

Vol 5 (1) ◽

pp. e000284 ◽

Cited By ~ 22

Author(s):

Joan T Merrill ◽

Richard Furie ◽

Victoria P Werth ◽

Munther Khamashta ◽

Jorn Drappa ◽

...

Keyword(s):

Lupus Erythematosus ◽

Type I Interferon ◽

Activity Index ◽

Statistical Significance ◽

Cutaneous Lupus Erythematosus ◽

Disease Activity Index ◽

Gene Signature ◽

Type I ◽

Tender Joint ◽

Interferon Gene

ObjectiveThis post hoc analysis compared anifrolumab 300 mg every 4 weeks with placebo on rash and arthritis measures with different stringency in patients with moderate to severe SLE (phase IIb; MUSE; NCT01438489). Subgroups were analysed by type I interferon gene signature (IFNGS test–high or test–low).MethodsRash was measured with the SLE Disease Activity Index 2000 (SLEDAI-2K), British Isles Lupus Assessment Group (BILAG) Index and modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI). Arthritis was evaluated using SLEDAI-2K, BILAG and swollen and tender joint counts. Outcomes were measured at week 52.ResultsMore anifrolumab-treated patients demonstrated resolution of rash by SLEDAI-2K versus placebo: 39/88 (44.3%) versus 13/88 (14.8%), OR (90% CI) 4.56 (2.48 to 8.39), p<0.001; improvement of BILAG: 48/82 (58.5%) versus 24/85 (28.2%), OR (90% CI) 3.59 (2.08 to 6.19), p<0.001; and ≥50% improvement by mCLASI: 57/92 (62.0%) versus 30/89 (33.7%), OR (90% CI) 3.31 (1.97 to 5.55), p<0.001. More anifrolumab-treated patients had improved arthritis by SLEDAI-2K versus placebo: 55/97 (56.7%) versus 42/99 (42.4%), OR (90% CI) 1.88 (1.16 to 3.04), p=0.032; and BILAG: 65/94 (69.1%) versus 47/95 (49.5%), OR (90% CI) 2.47 (1.48 to 4.12), p=0.003; and mean (SD) swollen and tender joint reductions: –5.5 (6.3) versus –3.4 (5.9), p=0.004. Comparable results were demonstrated in IFNGS test–high patients (n=151). In IFNGS test–low patients (n=50), substantial numerical differences in partial rash and arthritis responses were observed in anifrolumab-treated patients versus placebo, with statistical significance only for rash by BILAG in this small population.ConclusionsAnifrolumab treatment was associated with improvements versus placebo in specific SLE features of arthritis and rash using measures of different stringency. Although driven by robust data in the prevalent IFNGS test–high population, further evaluation in IFNGS test–low patients is warranted.

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