M Petri

Sifalimumab, a Human Anti–Interferon‐α Monoclonal Antibody, in Systemic Lupus Erythematosus: A Phase I Randomized, Controlled, Dose‐Escalation Study

Objective To evaluate the safety and tolerability of multiple intravenous (IV) doses of sifalimumab in adults with moderate-to-severe systemic lupus erythematosus (SLE). Methods In this multicenter, double-blind, placebo-controlled, sequential dose-escalation study, patients were randomized 3:1 to receive IV sifalimumab (0.3, 1.0, 3.0, or 10.0 mg/kg) or placebo every 2 weeks to week 26, then followed up for 24 weeks. Safety assessment included recording of treatment-emergent adverse events (AEs) and serious AEs. Pharmacokinetics, immunogenicity, and pharmacodynamics were evaluated, and disease activity was assessed. Results Of 161 patients, 121 received sifalimumab (26 received 0.3 mg/kg; 25, 1.0 mg/kg; 27, 3.0 mg/kg; and 43, 10 mg/kg) and 40 received placebo. Patients were predominantly female (95.7%). At baseline, patients had moderate-to-severe disease activity (mean SLE Disease Activity Index score 11.0), and most (75.2%) had a high type I interferon (IFN) gene signature. In the sifalimumab group versus the placebo group, the incidence of ≥1 treatment-emergent AE was 92.6% versus 95.0%, ≥1 serious AE was 22.3% versus 27.5%, and ≥1 infection was 67.8% versus 62.5%; discontinuations due to AEs occurred in 9.1% versus 7.5%, and death occurred in 3.3% (n = 4) versus 2.5% (n = 1). Serum sifalimumab concentrations increased in a linear and dose-proportional manner. Inhibition of the type I IFN gene signature was sustained during treatment in patients with a high baseline signature. No statistically significant differences in clinical activity (SLEDAI and British Isles Lupus Assessment Group score) between sifalimumab and placebo were observed. However, when adjusted for excess burst steroids, SLEDAI change from baseline showed a positive trend over time. A trend toward normal complement C3 or C4 level at week 26 was seen in the sifalimumab groups compared with baseline. Conclusion The observed safety/tolerability and clinical activity profile of sifalimumab support its continued clinical development for SLE.

Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort

We describe disease activity, damage, and the accrual of key autoantibodies in an inception systemic lupus erythematosus (SLE) cohort.

Anti-C1q antibodies have higher correlation with flares of lupus nephritis than other serum markers

Objective. Autoantibodies are important in the diagnosis and classification of systemic lupus erythematosus (SLE), but whether they correlate with changes in disease activity within individual patients is controversial. We assessed the association between changes in SLE global and renal activity and changes in several autoantibodies and cell adhesion molecules in patients with SLE. Methods. Stored sera collected at two or three clinic visits from each of 49 SLE patients (91% female, 59% African-American, 31% Caucasian, 10% other ethnicity, 38% under 30 years, 41% between 30–44 years, and 21% 45–63 years) were analyzed. The visits were chosen to include one visit with proteinuria, and one or two without, for each patient. Global disease activity was measured by the Physician’s Global Assessment (PGA), SELENA-SLEDAI (SLE Disease Activity Index modified to exclude anti-dsDNA and complement) and renal activity assessed by urine protein (by urine dipstick) and Renal Activity Score. Sera were assayed for anti-C1q, anti-chromatin, anti-dsDNA, anti-ribosomal P, monocyte chemotactic protein-1 (MCP-1), vascular cell adhesion molecule (VCAM) intercellular adhesion molecule (ICAM) and complement. The associations between changes in disease activity and changes in biomarker levels were assessed. Results. In terms of global disease activity, anti-C1q had the highest association with the PGA (pu2009=u20090.09) and was strongly associated with modified SELENA-SLEDAI (pu2009=u20090.009). In terms of renal activity, anti-C1q had the highest association with proteinuria (pu2009=u20090.079), and was strongly associated with Renal Activity Score (pu2009=u20090.006). Conclusion. Anti-C1q performed the best of the potential biomarkers, being significantly associated with the modified SELENA-SLEDAI and with the Renal Activity Score. This study indicates the potential superior utility of anti-C1q over anti-dsDNA and other measures to track renal activity.

SLE patients with renal damage incur higher health care costs

OBJECTIVESnTo compare costs and quality of life (QoL) between SLE patients with and without renal damage.nnnMETHODSnSeven hundred and fifteen patients were surveyed semi-annually over 4 yrs on health care use and productivity loss and annually on QoL. Cumulative direct and indirect costs (2006 Canadian dollars) and QoL (average annual change in SF-36) were compared between patients with and without renal damage [Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC/ACR DI)] using simultaneous regressions.nnnRESULTSnAt study conclusion, for patients with the renal subscale of the SLICC/ACR DI = 0 (n = 634), 1 (n = 54), 2 (n = 15) and 3 (n = 12), mean 4-yr cumulative direct costs per patient (95% CI) were

Interferon-γ polymorphisms in systemic lupus erythematosus

20,337 (

Erythrocyte sedimentation rate is a predictor of renal and overall SLE disease activity

18,815,

Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort

21,858),

Changes in Quality of Life in the First 5 Years of Disease in a Multicenter Cohort of Patients With Systemic Lupus Erythematosus

27,869 (

Long‐Term Safety and Efficacy of Epratuzumab in the Treatment of Moderate‐to‐ Severe Systemic Lupus Erythematosus: Results From an Open‐Label Extension Study

19,230,

Transient ischemic attack and stroke in systemic lupus erythematosus

36,509),