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 |
|---|---|---|---|---|
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) (www.clinicaltrials.gov 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 (www.clinicaltrials.gov 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 (www.clinicaltrials.gov 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 |