Table 3 |
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Novel therapeutic regimes in lupus nephritis targeting specific pathogenic molecules |
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Drug and reference |
Description of drug or target |
Mechanism of action |
Details of trial |
Outcome of trial |
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|
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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 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 (www.clinicaltrials.gov 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 |
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MEDI-545 (www.clinicaltrials.gov 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 |
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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. |
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Saxena et al. Arthritis Research & Therapy 2011 13:240 doi:10.1186/ar3378 |
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