Update on Clinical Trials in Systemic Lupus Erythematosus

Sonali Narain; Richard Furie


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

In This Article

Targeting B-cell Surface Molecules

Despite the failures of Exploratory Phase II/III SLE Evaluation of Rituximab (EXPLORER)[23] and Lupus Nephritis Assessment with Rituximab (LUNAR)[24] to demonstrate the superiority of rituximab to SoC in SLE and lupus nephritis, several observational studies[25–27] have reported the efficacy of rituximab in refractory disease, keeping the hope of a successful outcome alive.

Ocrelizumab, a humanized second-generation anti-CD20 mAb, also failed when both renal (BELONG) and nonrenal (BEGIN) trials in SLE were terminated early because of higher rates of opportunistic infections and lack of efficacy in EXPLORER trial.[23] Obinutuzumab, the first Fc-engineered, type II humanized IgG1 antibody against CD20, has been successfully used to treat lymphoproliferative disorders.[28] It has been shown to have greater antibody-dependent cytotoxicity and cellular phagocytosis compared with rituximab.[28,29] A phase II multicenter trial evaluating obinituzumab in proliferative lupus nephritis is ongoing.

Epratuzumab is a humanized monoclonal IgG antibody that binds CD22 on mature B cells[30,31] and unlike its anti-CD20 counterparts, does not fully deplete peripheral B cells.[32] After initial phase I success,[31] two similar large randomized placebo-controlled trials, ALLEVIATE-1 and 2, were performed. These trials were terminated because of disruption in drug supply, exploratory analysis noted efficacy in terms of clinical response, quality of life, reduction in steroid doses and safety.[33,34] The phase IIb EMBLEM study[35] used a novel composite primary end point, the British Isles Lupus Activity Group (BILAG)-based Combined Lupus Assessment (BICLA).[36] Epratuzumab at a cumulative dose of 2,400 mg significantly reduced disease activity as measured by BICLA at 12 weeks. Data from two phase III extrarenal trials, EMBODY 1 (n = 793) and EMBODY 2 (n = 791), were presented at the 2015 ACR meeting.[37] Neither study met their primary or secondary end points.