Update on Clinical Trials in Systemic Lupus Erythematosus

Sonali Narain; Richard Furie

Disclosures

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

In This Article

Costimulatory Blockade

AMG557 is a human IgG2 mAb that binds to B7-related protein-1 (B7RP-1/ICOSL) and inhibits its interaction with inducible costimulator, thus affecting T-cell differentiation, cytokine production and T–B cell interactions.[54] A phase I dose escalation study[54] of AMG557 showed no significant effects on disease activity or increases in adverse effects.

Abatacept is a cytotoxic T lymphocyte associated-4 Ig fusion protein that binds CD80 and CD86 with higher affinity than CD28, and thus blocks the costimulatory interaction between T and B lymphocytes, and subsequent T-cell activation.[55] A 12-month phase IIb flare prevention trial of abatacept in nonrenal SLE failed to meet its primary end point, but a subset of patients with polyarthritis demonstrated the greatest treatment differences as assessed by BILAG A or physician-assessed flares.[56] A 12-month phase II/III multicenter trial with 298 patients with proliferative lupus nephritis followed in 2014. Patients on background SoC dosed differently in African Americans versus Asian populations were randomized to receive placebo versus one of two abatacept treatment regimens. A stringently defined primary end point – confirmed complete renal response – was not achieved in the treatment arms.[57] Herpes zoster occurred more frequently in the abatacept groups. Posthoc analysis highlighted the importance of end point definitions in determining trial success as it was noted that by applying less stringent definitions of renal response, such as that used in the LUNAR study, a positive effect of abatacept could be demonstrated.[58,59] Another phase II trial of abatacept in addition to high-dose oral prednisone and intravenous cyclophosphamide (Euro Lupus regimen) in 134 patients with proliferative lupus nephritis was published 9 months later.[60] Complete response rates measured at week 24 and subsequently at week 52 were no different in the abatacept versus placebo groups.[60] Trials in SLE are ongoing in patients with arthritis as well as one phase III lupus nephritis with modifications made to entry criteria and end points.

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