METHODS: In this phase Ib, randomised, multiple-dose escalation study (NCT00818948), subjects without LN were randomised to subcutaneous AMG 811 (6, 20 or 60 mg) or placebo and subjects with LN were randomised to subcutaneous AMG 811 (20, 60 or 120 mg) or placebo every four weeks for three total doses. Outcomes included incidence of adverse events (AEs); pharmacokinetics; levels of serum proteins (CXCL-10, interleukin 18, monocyte chemotactic protein-1); changes in gene transcript profiles and clinical parameters (Safety of Estrogen in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores, proteinuria, anti-double-stranded DNA (anti-dsDNA) antibodies, C3 complement, C4 complement).

RESULTS: Fifty-six subjects enrolled (28 SLE without LN; 28 with LN). Baseline mean SELENA-SLEDAI scores were 2.2 and 12.0 for SLE subjects without and with LN, respectively. Most subjects reported an AE; no meaningful imbalances were observed between AMG 811 and placebo. Pharmacokinetic profiles were similar and mostly dose-proportional in subjects without or with LN. AMG 811 treatment reduced CXCL-10 protein levels and blood-based RNA IFN-γ Blockade Signature compared with placebo. Reductions were less pronounced and not sustained in subjects with LN, even at the highest dose tested, compared with subjects without LN. No effect on SELENA-SLEDAI scores, proteinuria, C3 or C4 complement levels, or anti-dsDNA antibodies was observed.

CONCLUSION: AMG 811 demonstrated favourable pharmacokinetics and acceptable safety profile but no evidence of clinical impact. IFN-γ-associated biomarkers decreased with AMG 811; effects were less pronounced and not sustained in LN subjects.

METHODS: Sixty patients were randomised to receive IV dexmedetomidine 0.5 μg.kg-1 (Group DEX, n = 30) or IV saline (Group P, n = 30). General anaesthesia was maintained with Sevoflurane: oxygen: air, titrated to BIS 40-60. Pain intensity, sedation, rescue analgesics, nausea/vomiting and resumption of daily activities were recorded at 1 h, and postoperative day (POD) 1-5.

RESULTS: Group DEX patients had significant reduction in sevoflurane minimum alveolar concentration (MAC), mean (SD) DEX vs. Placebo 0.6 (0.2) vs. 0.9 (0.1), p = 0.037; reduced postoperative resting pain at 1 h (VAS 0-10) (mean (SD) 1.00 (1.84) vs. 2.63 (2.78), p = 0.004), POD 1 (mean (SD) 1.50 (1.48) vs. 2.87 (2.72), p = 0.002), POD 2 (0.53 (0.97) vs. 1.73 (1.96), p = 0.001) and POD 3 (0.30 (0.75) vs. 0.89 (1.49), p = 0.001). DEX patients also had less pain on movement POD 1 (3.00 (2.12) vs. 4.30 (3.10), p = 0.043) and POD 2 (2.10 (1.98) vs. 3.10 (2.46), p = 0.040), with higher resumption of daily activities by 48 h compared to placebo, 87% vs. 63%, p = 0.04.

CONCLUSIONS: We conclude that a single dose of dexmedetomidine was a useful adjuvant in reducing MAC and postoperative pain (at 1 h and POD 1-3), facilitating faster return to daily activities by 48 h.