Therapy | Mode of action | Clinical trial | Preliminary results |
---|---|---|---|
Abatacept (CTLA4-Ig) | Blocks CD28-mediated costimulation | Phase II, placebo-controlled trial. Two ongoing trials in lupus nephritis | In moderate-to-severe extrarenal disease the adjudicated BILAG-based primary and secondary endpoints were not met after 1 year of treatment |
Abetimus (LJP 394) | Blocks the production of anti-dsDNA antibodies | Phase II/III, randomised placebo-controlled trial in lupus nephritis | Improvement in quality of life and reduction in anti-dsDNA levels but did not prolong time to renal flare |
AMG 557 (anti-B7RP-1 mAb) | Blocks ICOS-B7RP-1 interaction | Phase I trial | Ongoing trial |
Anakinra (IL-1 receptor antagonist) | Blocks IL-1 signalling | Open-label study | Clinical and serological improvement |
Anti-IL-10 mAb | Blocks IL-10 | Phase I, open-label trial | Skin/joint disease and SLEDAI improved during the 6-month follow-up. Reduction in steroid dose |
Atacicept (TACI-Ig) | Soluble TACI receptor that binds to BLyS and APRIL | Phase I, placebo-controlled trial. Ongoing phase II/II trial in generalised SLE. A phase II/III study in lupus nephritis terminated due to toxicity | IV atacicept was generally tolerated in patients with mild-to-moderate SLE. Reduction in B cells and immunoglobulin levels |
Belimumab (anti-BLyS) | Blocks BLyS | Phase II/III, placebo-controlled trial (under FDA review) | In seropositive SLE, belimumab resulted in moderate improvement in disease activity through 3 years of continuous treatment. The frequency of flares also declined |
BG9588 (anti-CD40L mAb) | Blocks CD40-CD40L interaction | Phase II/III open-label trial in lupus nephritis | A short course of BG9588 treatment reduced anti-dsDNA antibodies, increased C3 concentrations, and decreased haematuria. The trial was terminated prematurely due to thromboembolic events |
Eculizumab (anti-C5 mAb) | Inhibits C5 and membrane attack complex formation | Phase I, open-label trial | Safe and well tolerated |
Edratide (hCDR1) | Tolerogenic peptide | Phase II, placebo-controlled trial (terminated due to lack of efficacy) | Improvement in anti-dsDNA titres, proteinuria and leucopenia. No improvement in SLEDAI (24 weeks) |
Epratuzumab (anti-CD22 mAb) | Modulation of B cell signalling | Phase II, placebo-controlled trials (discontinued due to manufacturing issues) | Clinically meaningful improvements in health-related quality of life and disease activity over weeks 12–48. Steroid-sparing effect |
Glutathione (N-acetylcysteine) | Antioxidant agent | Phase II, placebo-controlled trial | Ongoing trial |
Infliximab (anti-TNF) | Blocks TNF | Open-label trial. Ongoing open-label trial in lupus membranous nephropathy | Infliximab in combination with azathioprine resulted to reduction in proteinuria in lupus nephritis |
Laquinimod | Immuno-modulatory agent | Phase II trials in lupus nephritis and arthritis | Ongoing trials |
MEDI-545 (sifalimumab) (anti-IFNα mAb) | Blocks IFNα | Phase I trial. Ongoing phase II trial | Neutralisation of other signalling pathways including GM-CSF, TNF, IL-10, IL-1β and BAFF in SLE patients |
NOX-E36 spiegelmer | Blocks MCP1 (CCL2) | Phase I trial | Ongoing trial |
Ocrelizumab (humanised anti-CD20 mAb) | Depletion of B cells | Phase II/III trials in active lupus and lupus nephritis | Ongoing trials |
Spliceosomal peptide P140 (IPP-201101) | Possible tolerance spreading | Phase II/III trials | 50% of the patients in the effective dose group showed a SLEDAI reduction of at least 50%, and 80% of the patients had reductions in anti-dsDNA titres. Drug was well tolerated |
Rituximab (anti-CD20 mAb) | Depletion of B cells | Phase II/III, randomised placebo-controlled trials in lupus and lupus nephritis | No difference in primary and secondary outcomes (BILAG-defined response, renal response) compared to placebo |
Rontalizumab (rec human anti-IFN mAb) | Blocks IFNα | Phase II, randomised placebo-controlled trial | Ongoing trial |
SBI-087 (anti-CD20 mAb) | Depletion of B cells | Phase I trial | Ongoing trial |
Tocilizumab (anti-IL-6 receptor mAb) | Blocks IL-6 | Phase I, open-label trial | Reduction in acute phase reactants, immunoglobulin, and anti-dsDNA levels. Swollen joint counts, SLEDAI and SLAM scores decreased |
BILAG, British Isles Lupus Assessment Group; BlyS, B lymphocyte stimulator; IL, interleukin; IFN, interferon; GM-CSF, granulocyte/macrophage colony stimulating factor; mAb, monoclonal antibody; SLE, systemic lupus erythematosus; SLEDAI, systemic lupus erythematosus disease activity index; TNF, tumour necrosis factor.