Table 1 Compounds of interest as new tools for the treatment of systemic lupus erythematosus
From: Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects
Compound | Product description | Type of study | Results/comments | Reference |
|---|---|---|---|---|
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] | ||
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. | ||||
Greater number of participants experiencing adverse events. | ||||
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] | ||
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] |