Update on Clinical Trials in Systemic Lupus Erythematosus

Sonali Narain; Richard Furie


Curr Opin Rheumatol. 2016;28(5):477-487. 

In This Article

Anti-interferonα Receptor Antibodies

Anifrolumab (MEDI-546) is a human IgG1k mAb directed against subunit 1 of the type I IFN receptor and thus blocks the effects of all type I IFNs.[75] A study[76] in Japanese patients with SLE that focused on the pharmacokinetics and pharmacodynamics of sifalimumab (n = 30) and anifrolumab (n = 17) demonstrated that anifrolumab had a far more robust and sustained suppression of the IFN gene signature (IFNGS) compared with sifalimumab. More encouraging data were reported in 2015.[77] In a phase II study, 351 patients with chronic, moderately to severely active SLE with an inadequate response to SoC were randomized to receive anifrolumab (300 mg and 1000 mg intravenous) or placebo. Patients were stratified by SLEDAI score, oral corticosteroid dose and IFNGS (IFN high versus IFN low). The primary end point was a composite of SRI 4 response at day 169 with a sustained reduction of OCS (<10 mg/day and <=day 1 dose maintained between days 85 and 169). The primary end point was met, with a more favorable result seen in the 300 mg dose group (placebo: 17.6% versus anifrolumab: 300 mg: 34.3%, P = 0.014; 1000 mg: 28.8%, P = 0.063). Similar results were noted in the secondary SRI end points at day 365 (placebo: 25.5% versus anifrolumab: 300 mg: 51.5%, P < 0.001; 1000 mg: 38.5% P = 0.048). The effect sizes were even greater in the patients with high baseline IFN signatures. Despite comparable overall rates of adverse events, higher frequencies of influenza and Herpes zoster (placebo: 2.0%; 300 mg: 5.1%; 1000 mg: 9.5%) were reported in the anifrolumab cohorts. Several trials with anifrolumab are underway at this time, including a phase II open-label extension study, two phase III studies in individuals with moderately to severely active SLE and a trial in proliferative lupus nephritis. Medimmune/Astra Zeneca has also announced the development of a subcutaneous form of anifrolumab.