|Biologic therapies proposed for SLEa|
|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|||
|• 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|||
|• 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|||
|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|||
|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|||
|• 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|||
|• 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|||
|• 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.
Gatto et al.
Gatto et al. BMC Medicine 2014 12:30 doi:10.1186/1741-7015-12-30