ANIFROLUMAB, AN ANTI-INTERFERON-ALPHA RECEPTOR MONOCLONAL ANTIBODY, IN MODERATE TO SEVERE SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Background: Increased activity of the type I interferon (IFN) pathway is central to the pathogenesis of SLE. Blocking the type I receptor may reduce SLE activity more effectively than inhibiting IFN-α alone. Objectives: Efficacy and safety of anifrolumab were assessed in a Phase IIb, randomized, double-blind, placebo-controlled study of adults with moderate to severe SLE (the MUSE study). Methods: 305 patients were treated for 48 weeks with intravenous anifrolumab (300 mg or 1000 mg) or placebo, in addition to standard-of-care medications. Randomization was stratified by SLE Disease Activity Index 2000 (SLEDAI-2K) score (<10 or ≥10), oral corticosteroid (OCS) dose (<10 or ≥10 mg/day), and IFN gene signature status (high vs. low) based on a 4-gene expression assay. The primary endpoint was the percentage of patients achieving an SLE Responder Index [SRI(4)] response at Day 169 with sustained reduction of OCS (<10 mg/day and ≤Day 1 dose from Day 85 to 169). Results: The primary endpoint was met by more anifrolumab-treated patients [placebo vs. 300 mg vs. 1000 mg: 17.6%, 34.3% (p=0.014), 28.8% (p=0.063)] with greater effect sizes observed in the 75% of patients who had a high baseline IFN signature [13.2%, 36.0% (p=0.004), 28.2% (p=0.029)]. At Day 365 more anifrolumab-treated patients achieved SRI(4) responses [40.2%, 62.6%, (p<0.001), 53.8%, (p=0.043)], BILAG-based Composite Lupus Assessment (BICLA) [25.7%, 53.5% (p<0.001), 41.2% (p=0.018)], modified SRI(6) [28.4%, 49.5% (p=0.002), 44.7% (p=0.015)], and SLEDAI-2K ≤2 [17.6%, 35.4% (p=0.004), 32.7% (p=0.012)]. Major clinical response (BILAG “C” or better in all domains at Day 169 maintained to Day 365) was achieved by 6.9%, 19.2% (p=0.012), and 17.3% (p=0.025) of patients. BILAG “A” flares were reported in more placebo- vs. anifrolumab-treated patients (16.7%, 9.1%, 10.6%). In patients with baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score ≥10, more anifrolumab-treated patients attained a ≥50% reduction by Day 365 [30.8%, 63.0% (p=0.013), 58.3% (p=0.077)]. In patients with ≥8 swollen and ≥8 tender joints at baseline more anifrolumab-treated patients achieved ≥50% decrease in joint count [48.6%, 69.6% (p=0.038), 64.6% (p=0.156)]. Although steroid tapering was not mandated, OCS reduction to ≤7.5 mg/d at Day 365 was achieved by 26.6%, 56.4%, and 31.7% of patients. The observed benefits were driven by results in the IFN-high subpopulation (figure). Median suppression of 21 IFN-regulated genes was ∼90% for both doses of anifrolumab. Patients in the placebo group had the lowest incidence of Herpes zoster (2.0%, 5.1%, 9.5%) and cases reported as influenza (2.0%, 6.1%, 7.6%); there were no differences in the incidence of serious adverse events (18.8%, 16.2%, 17.1%). The incidence of infusion-related reactions was similar (5.9%, 2.0%, 3.8%). Conclusions: Anifrolumab significantly reduced disease activity across all clinical endpoints. Enhanced effects in IFN-high patients support the pathobiology of this treatment strategy. Acknowledgement: Funded by MedImmune. Editorial assistance: K Alexander, QXV Comms, an Ashfield business, UK Disclosure of Interest: R. Furie Consultant for: MedImmune, J. Merrill Grant/research support from: MedImmune; Genentech/Roche, Consultant for: Medimmune, Genentech/Roche, Neovacs, V. Werth Consultant for: MedImmune, M. Khamashta: None declared, K. Kalunian Grant/research support from: MedImmune, Consultant for: AstraZeneca, P. Brohawn Shareholder of: AstraZeneca, Employee of: MedImmune, G. Illei Shareholder of: AstraZeneca, Employee of: MedImmune, J. Drappa Shareholder of: AstraZeneca, Employee of: MedImmune, L. Wang Employee of: MedImmune, S. Yoo Shareholder of: AstraZeneca; Regenx Bio, Consultant for: Regenx Bio DOI: 10.1136/annrheumdis-2016-eular.3919Citation: Annals of the Rheumatic Diseases, volume 75, supplement 2, year 2016, page 168Session: SLE: What will it be and how will it be treated 5 years from now (Oral Presentations )