Table 1 |
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Compounds of interest as new tools for the treatment of systemic lupus erythematosus |
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| Compound |
Product description |
Type of study |
Results/comments |
Reference |
|
|
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| Atacicept |
Fusion protein (TACI-Ig) B-lymphocyte stimulator inhibition |
Phase Ib, double-blind, placebo-controlled, dose-escalating trial. Patients with mild
to moderate SLE were enrolled. |
Dose-dependent reduction in immunoglobulin levels and B-cell numbers. Well tolerated. |
[3] |
| 15-Deoxyspergualin or gusperimus |
Binds to HSC70/hsp73 heatshock protein |
Case report: 3 SLE patients, safety evaluation. Treatment was performed by 9 cycles
(1 cycle = 15-deoxyspergualin administration for 14 days with a break of 7 days). |
15-Deoxyspergualin was well tolerated but 2/3 patients had nonsevere infectious episodes. |
[5] |
| FK506 or Tacrolimus |
Inhibition of calcineurin |
Retroprospective review: analysis of 5 studies (only one randomized controlled trial),
including a total of 60 SLE patients with cutaneous lesions. |
Efficacy in cutaneous lesions of SLE, but weaker efficacy in subacute cutaneous LE
or in discoid LE. Studies involving only a small number of patients and no control
group. |
[7] |
| Rapamycin/sirolimus/rapamune |
mTOR inactivation |
Open-label study: 9 SLE patients treated unsuccessfully with immunosuppressive medications.
Rapamycin was given orally (2 mg/day). |
Reduction of BILAG score, of SLEDAI score and of prednisolone use compared with pre-rapamycin
treatment. |
[8] |
| Celecoxib or celebrex |
Cyclooxygenase-2 inhibition |
Retrospective review of medical records for 50 patients treated with celecoxib. |
Diminution of inflammation and good safety profile. |
[10] |
| Prospective trial including 51 patients. |
Reduction of SLEDAI score and no increase of coagulability. |
[11] |
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| Pentoxiphylline |
Xanthine-derivative phosphodiesterase inhibitor |
Open-label study: 11 SLE patients with refractory nephritis: class III, IV or V, proteinuria
≥ 3 g/24 hours. |
Decrease of proteinuria (from 5.5 to 2.0, P = 0.003). No patients discontinued the study due to side effects. |
[13] |
| Tamoxifen |
Estrogen antagonist |
Double-blind crossover trial: 11 females with stable SLE. |
No improvement of disease activity and 2 patients deteriorated. |
[18] |
| DHEA or prasterone |
Androgen |
Review: analysis of randomized controlled trials (7) comparing DHEA with a placebo
in SLE patients (842 participants). |
Little clinical effect on disease activity for patients with moderate disease. |
[20] |
| Modest but significant improvement in health-related quality of life. |
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| Greater number of participants experiencing adverse events. |
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| Fulvestrant or faslodex |
Estrogen receptor downregulator |
Double-blind, placebo-controlled: 20 premenopausal SLE women with moderate SLEDAI
received either 250 mg fulvestran intramuscularly for 12 months (10 patients) or placebo
(10 patients). |
Improvement of SLEDAI but not of serological markers, routine laboratory tests nor
bone density. Medications for lupus reduced in the fulvestrant group. |
[21] |
| Bromocriptine |
Dopamine agonist inhibition of prolactine secretion |
Open-label trial: 7 active SLE patients treated daily during 6 to 9 months. |
Serum prolactine and anti-dsDNA suppressed, SLEDAI decreased (16 to 5.9). |
[24] |
| Double-blind, randomized, placebo-controlled: 66 SLE patients (36 bromocriptine, 30
placebo), treated daily and followed for 2 to 17 months. |
Significant decreased of SLEDAIscore (0.9 vs. 2.6 in control group), decreased mean
number of flares/patient/month (0.08 vs. 0.18 in control group). |
[25] |
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| LJP394/abetimus sodium/riquent |
Toleragen molecule; 4 strands of ds-oligonucleotides (20-mer) linked through a triethylene
glycol-based platform |
Phase III, randomized, placebo-controlled trial: 317 SLE patients with a history of
renal flares and anti-dsDNA levels >15 IU/ml. Patients received 100 mg/week for up
to 22 months. |
Abetimus did not prolong time to renal flare, time to initiation of high-dose corticosteroid
and/or cyclophosphamide treatment, or time to major SLE flare, but decreased anti-dsDNA
antibody levels (P < 0.0001). |
[27] |
| Lupuzor RIHMVYSKRSGK PRGYAFIEY |
21-mer peptide P140 (phosphoserine at position 140) |
Phase IIa: open-label, dose-escalating trial. 20 patients with moderate SLE were enrolled.
Lupuzor was given subcutaneously (200 μg or 1 mg). |
Diminution of anti-dsDNA antibody levels and of SLEDAI score in the group that received
200 μg peptide. |
[31] |
|
|
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|
Published trials only are presented. BILAG, British Isles Lupus Assessment Group; DHEA, dehydroepiandrosterone; ds, double-stranded; mTOR, mammalian target of rapamycin; SLE, systemic lupus erythematosus; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index. |
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Monneaux and Muller Arthritis Research & Therapy 2009 11:234 doi:10.1186/ar2711 |
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