Table 1 Compounds of interest as new tools for the treatment of systemic lupus erythematosus

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.

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.

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.

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.

Celecoxib or celebrex

Cyclooxygenase-2 inhibition

Retrospective review of medical records for 50 patients treated with celecoxib.

Diminution of inflammation and good safety profile.

Prospective trial including 51 patients.

Reduction of SLEDAI score and no increase of coagulability.

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.

Tamoxifen

Estrogen antagonist

Double-blind crossover trial: 11 females with stable SLE.

No improvement of disease activity and 2 patients deteriorated.

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.

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.

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).

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).

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).

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.