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Table 3 Novel therapeutic regimes in lupus nephritis targeting specific pathogenic molecules

From: Lupus nephritis: current update

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) ( 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 ( 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 ( 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
  1. 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.