Pregnancy outcomes in the omalizumab pregnancy registry and a disease-matched comparator cohort.

BACKGROUND: The Observational Study of the Use and Safety of Xolair (omalizumab) during Pregnancy (EXPECT) pregnancy registry was a prospective observational study established in 2006 to evaluate perinatal outcomes in pregnant women exposed to omalizumab and their infants. OBJECTIVE: This analysis compares EXPECT outcomes with those from a disease-matched population of pregnant women not treated with omalizumab. Data from a substudy of platelet counts among newborns are also presented. METHODS: The EXPECT study enrolled 250 women with asthma exposed to omalizumab during pregnancy. The disease-matched external comparator cohort of women with moderate-to-severe asthma (n = 1153), termed the Quebec External Comparator Cohort (QECC), was created by using data from health care databases in Quebec, Canada. Outcome estimates were age adjusted based on the maternal age distribution of the EXPECT study. RESULTS: Among singleton infants in the EXPECT study, the prevalence of major congenital anomalies was 8.1%, which was similar to the 8.9% seen in the QECC. In the EXPECT study 99.1% of pregnancies resulted in live births, which was similar to 99.3% in the QECC. Premature birth was identified in 15.0% of EXPECT infants and 11.3% in the QECC. Small for gestational age was identified in 9.7% of EXPECT infants and 15.8% in the QECC. CONCLUSION: There was no evidence of an increased risk of major congenital anomalies among pregnant women exposed to omalizumab compared with a disease-matched unexposed cohort. Given the observational nature of this registry, however, an absence of increased risk with omalizumab cannot be definitively established.

Clinical correlates of serum pigment epithelium-derived factor in type 2 diabetes patients.

AIM: To determine if serum pigment epithelium-derived factor (PEDF) levels in Type 2 diabetes are related to vascular risk factors and renal function. METHODS: PEDF was quantified by ELISA in a cross-sectional study of 857 male Veterans Affairs Diabetes Trial (VADT) subjects, and associations with cardiovascular risk factors and renal function were determined. In a subset (n=246) in whom serum was obtained early in the VADT (2.0±0.3 years post-randomization), PEDF was related to longitudinal changes in renal function over 3.1 years. RESULTS: Cross-sectional study: In multivariate regression models, PEDF was positively associated with serum triglycerides, waist-to-hip ratio, serum creatinine, use of ACE inhibitors or angiotensin receptor blockers, and use of lipid-lowering agents; it was negatively associated with HDL-C (all p<0.05). Longitudinal study: PEDF was not associated with changes in renal function over 3.1 years (p>0.09). CONCLUSIONS: Serum PEDF in Type 2 diabetic men was cross-sectionally associated with dyslipidemia, body habitus, use of common drugs for blood pressure and dyslipidemia, and indices of renal function; however, PEDF was not associated with renal decline over 3.1years.

Apolipoprotein-defined and NMR lipoprotein subclasses in the veterans affairs diabetes trial.

AIMS: The VADT was a randomized clinical trial designed to assess the effect of intensive vs. standard glucose management on cardiovascular events in Type 2 diabetes. At the end of the study, intensive management failed to improve outcomes. We performed plasma lipoprotein subclass analyses to yield new information on the effects of study randomization on cardiovascular risk. METHODS: This is a cross-sectional study of a subset of the VADT (740 men: 368 intensive; 372 standard), conducted at least six months (mean±SD: 2.1±0.8years) post-randomization. Conventional lipids, apolipoprotein-defined (ADLS) lipoprotein subclasses, ApoCIII, ApoE, and Nuclear Magnetic Resonance (NMR) lipoprotein subclasses were determined. RESULTS: In intensive vs. standard groups, conventional lipids and ADLS did not differ significantly. However, with intensive treatment, NMR-determined large and medium VLDL subclasses and VLDL diameter were lower, LDL diameter was higher, medium HDL was higher, and small HDL was lower (all p<0.05). Also, ApoCIII levels were lower (p<0.01). CONCLUSIONS: In a subset of diabetic men from the VADT, intensive glucose management did not affect conventional lipids or ADLS, but had some beneficial effects on particle characteristics as defined by NMR and on ApoCIII.

Observation on renal outcomes in the Veterans Affairs Diabetes Trial.

OBJECTIVE: The Veterans Affairs Diabetes Trial (VADT) was a randomized, prospective, controlled trial of 1,791 patients with type 2 diabetes to determine whether intensive glycemic control would reduce cardiovascular events compared with standard control. The effect of intensive glycemic control and selected baseline variables on renal outcomes is reported. RESEARCH DESIGN AND METHODS: Baseline mean age was 60.4 years, mean duration of diabetes was 11.5 years, HbA(1c) was 9.4%, and blood pressure was 132/76 mmHg. The renal exclusion was serum creatinine >1.6 mg/dL. Renal outcomes were sustained worsening of the urine albumin-to-creatinine ratio (ACR) and sustained worsening by one or more stages in the estimated glomerular filtration rate (eGFR). RESULTS: Intensive glycemic control did not independently reduce ACR progression but was associated with a significant attenuation in the progression of ACR in those who had baseline photocoagulation, cataract surgery, or both. The beneficial effect of intensive glycemic control increased with increasing BMI and with decreasing diastolic blood pressure (DBP). Intensive glycemic control was associated with less worsening of eGFR with increasing baseline ACR and insulin use. Baseline systolic blood pressure, triglycerides, and photocoagulation were associated with worsening of eGFR. CONCLUSIONS: Intensive glycemic control had no significant effect on the progression of renal disease in the whole cohort but was associated with some protection against increasing ACR in those with more advanced microvascular disease, lower baseline DBP, or higher baseline BMI and on worsening of eGFR in those with high baseline ACR.