Update on Clinical Trials in Systemic Lupus Erythematosus

Sonali Narain; Richard Furie


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

In This Article

Targeting Interferonα

Rontalizumab is a humanized IgG1 monoclonal anti-IFNα antibody that binds multiple subtypes of IFNα.[68] In an early trial, rontalizumab was well tolerated and at higher doses induced a rapid decline in the expression of IFN-regulated genes after the first dose that was sustained up to 3 months. However, IFNα signature in patients with high interferon signature metrics (ISM) did not decline to levels observed in patients with low ISM or healthy individuals.[69] The phase II Rontalizumab in Systemic Lupus Erythematosustrial[70] enrolled two placebo-controlled cohorts (n = 159) that received rontalizumab intravenous (750 mg q4W; n = 81) versus SC (300 mg q2W; n = 78). This study was unique in that no immunosuppressive therapies were permitted after randomization. The trial did not meet its primary end point of an improvement in BILAG compared with baseline without any new flares or use of additional therapies. In an exploratory analysis, there was a trend toward clinical improvement in patients with low ISM at baseline.

Sifalimumab (MEDI-545) is a fully human IgG1k mAb that neutralizes multiple IFNα subtypes except IFNα21.[71] Early clinical trials in SLE demonstrated improved skin lesions, disease activity and acceptable safety profiles.[72,73] In a phase IIb dose escalating study[74] in individuals with moderate-to-severe SLE despite SoC, 431 patients were randomized – stratified by disease activity, IFN 4-gene signature and geographic region – to monthly intravenous sifalimumab or placebo for 1 year. The primary efficacy end point, SRI 4 response at day 365, was achieved in patients receiving sifalimumab (200 mg: 58.3%, 600 mg: 56.5% and 1200 mg: 59.8% versus placebo 45.4%; P = 0.053). Patients in the treatment groups also had improvement in their mucocutaneous disease, arthritis and fatigue. Although adverse events were comparable, more Herpes zoster infections occurred in the sifalimumab groups (4.6, 3.7 and 8.4%, respectively, versus placebo 0.9%).