Table 3

Novel therapeutic regimes in lupus nephritis targeting specific pathogenic molecules

Drug and reference

Description of drug or target

Mechanism of action

Details of trial

Outcome of trial

LPJ394 (riquent, abetimus sodium) [131,132]

Four dsDNA helices coupled to polyethylene scaffold

Neutralizes anti-DNA antibodies in serum and tolerizes anti-DNA B cells

n = 230, classes III to V lupus nephritis; randomized, placebo-controlled, for 76 weeks

Anti-DNA and complement profiles improved with LJP394, but no significant difference in time to renal flares between the two groups

Rituximab [133]

Chimeric antibody to CD20 on B cells

Agent targets and silences or removes B cells (some of which produce autoantibodies)

n = 10 lupus nephritis patients, 375 mg/m2, 4 weekly infusions, + oral CS; duration 12 months

5/10 achieved complete remission sustained for 1 year; 3/10 had partial remission

Epratuzumab [134]

Humanized antibody to CD22 on B cells

Agent targets and silences or removes B cells (some of which produce autoantibodies)

n = 14 (4 with nephritis); open-label study. Four doses of 360 mg/m2 given every 2 weeks; duration 32 weeks

Total BILAG scores decreased by ≥50% in all 14 patients at some point during the study. It was well tolerated

Belimumab (lymphostat B) [135]

Humanized antibody to Blys (or BAFF)

Agent blocks activation of B cells by countering Blys activation of B cells

n = 449 (22 to 35% with nephritis); phase II randomized double-blind placebo-controlled study. Patients receive placebo or 1, 4 or 10 mg/kg belimumab at days 0, 14, 28 and then every 28 days + standard-of-care treatment; duration 52 weeks

No significant differences in primary end-points (reduction in SELENA-SLEDAI scores or time to renal flares). However, patients on belimumab had significantly better physicians' subjective assessment scores and Short Form 36 scores)

Orencia (abatacept) ( webcite ID: NCT00774852)

Fusion protein of CTLA4 linked to Fc portion of human IgG1

Agent blocks T-cell:B-cell cross-talk by blocking CD28-CD80/CD86 interactions

n = 100; randomized, double-blind, controlled, phase II multicenter trial of CTLA4Ig (abatacept) plus cyclophosphamide vs. cyclophosphamide alone in the treatment of lupus nephritis

Currently recruiting

Rontalizumab ( webcite ID: NCT00962832)

Humanized antibody to type 1 interferon

Agent blocks the function of the cytokine, interferon type 1

n = 210; phase II, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of rontalizumab in patients with moderately to severely active systemic lupus erythematosus

Active: not recruiting patients at present

MEDI-545 ( webcite ID: NCT00657189)

Fully human antibody to IFN-α

Agent blocks the function of the cytokine, interferon type 1

n = 80; phase 2A, randomized, doubleblind, placebo-controlled, paralleldose study to evaluate the safety and tolerability of multiple subcutaneous doses of MEDI-545, in subjects with SLE

Active: not recruiting patients at present

BILAG, British Isles Lupus Assessment Group; CS, corticosteroids; SELENA, Safety of Estrogens in Lupus Erythematosus: National Assessment; SLE, systemic lupus erythematosus; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index.

Saxena et al. Arthritis Research & Therapy 2011 13:240   doi:10.1186/ar3378