Table 1.

Biologic therapies proposed for SLE ^a

	Drug	Type of molecule	RCT phase	Pros for use in SLE	Cons for use in SLE	References
Anti-B cell therapies	Rituximab	Chimeric anti-CD20 mAb	Phase III	• Significantly decreased anti-dsDNA antibody titers and increased complement levels vs. placebo. Significantly decreased lupus non-renal flares in Hispanic and African American patients	• Did not significantly improve lupus outcome in either renal or non-renal SLE in large cohorts of SLE patients	[2,3]
	Ocrelizumab	Humanized anti-CD20 mAb	Phase III	• Significantly increased complement levels and decreased anti-dsDNA titers through week 48 vs. placebo	• No significant improvement in renal outcome	[15]
				• Induced numerically (non-statistically) significant greater renal response vs. placebo	• Serious infections in treated patients vs. placebo when added to MMF
	Epratuzumab	Humanized anti-CD22 mAb	Phase IIb	• Provided clinical improvement in patients receiving ≥2,400 mg cumulative dose	• No significant BILAG improvement after 12 weeks treatment vs. placebo	[5]
				• Steroid-sparing effect
	Belimumab	Fully human anti-BlyS mAb	Phase III	• Significant improvement in moderate-persistent active SLE outcome and decreased flare rates in phase III RCTs (met primary endpoints)	• No BILAG assessment	[8,9]
					No data on CNS or severe renal involvement
				• Significant decrease in anti-dsDNA antibody titers	• No advantages by treatment continuation through week 76 (but in post-hoc analysis)
				• Steroid-sparing effect
	Atacicept	Soluble fully human recombinant anti-APRIL fusion protein	Phase II	• Not availableb	• Serious infections and decreased immunoglobulin levels in patients receiving MMF or corticosteroids prior to atacicept	[6]
Anti-co-stimulatory molecules	Abatacept	CTLA4-Ig fusion protein	Phase IIb	• Reduced BILAG A polyarthritis flares in a phase IIb RCT	• Did not reduce overall disease flares vs. placebo in either renal or non-renal SLE	[10]
	IDEC-131	Humanized anti-CD40 ligand mAb	Phase II	• Ameliorated SLEDAI in a phase II RCT	• No significant superiority to placebo	[11,12]
					• Increased risk of thromboembolic events
Anti-cytokines therapies	Infliximab	Chimeric anti-TNF soluble mAb	No RCT performed	• Effective on refractory arthritis, nephritis and skin lesions in open-label studies	• Severe adverse events following treatment, for example, thrombosis, infections	[16,17]
				• Reduction in SLEDAI and SLICC-DI in pilot studies after short-term induction treatment	• Induction of pathological/pathogenetic autoantibodies (anti-dsDNA, anti-phospholipid antibodies)
					• Increase in IFNα levels following protracted administration
	Tocilizumab	Humanized IgG1 anti-IL6R mAb	Phase I	• Significantly reduced SELENA-SLEDAI score (main improvement on arthritis)	• Neutropenia and serious infections	[18]
				• Significantly reduced IgG anti-dsDNA antibody levels	• No data on severe SLE
	Anakinra	Non glycosylated IL1Ra	No RCT performed	• Improved arthritis in an open-label trial	• No long-lasting effect	[4]
					• No extensive data are available due to very low patients number
	Sifalimumab	Human mAb blocking multiple IFNα subtypes	Phase I	• Significantly reduced the rate of disease flares vs. placebo	• No data on severe SLE	[19]
				• Lower request of immunosupressor vs. placebo

^aOnly biologic therapies for which published clinical studies are currently available are listed.

^bthe study was prematurely terminated and no efficacy measures were undertaken.

anti-dsDNA, anti-double stranded DNA; APRIL, A PRoliferation Inducing Ligand; BILAG, British Isles Lupus Assessment Group; BLyS, B Lymphocyte Stimulator; CNS, central nervous system; IFNα, interferon alpha; IgG, class G immunoglobulin; IL1Ra, interleukin 1 receptor antagonist; IL6R, interleukin-6 receptor; mAb, monoclonal antibody; MMF, mycophenolate mofetil; RCT, randomized controlled trial; SLE, systemic lupus erythematosus; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index; SLICC-DI, Systemic Lupus International Collaborating Clinics group Damage Index; TNFα, tumor necrosis factor alpha.