Table 1 Biologic therapies proposed for SLE ^a

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 available^b

• Serious infections and decreased immunoglobulin levels in patients receiving MMF or corticosteroids prior to atacicept

[6]

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

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