B-type and N-terminal pro-B-type natriuretic peptides in heart failure

The thesis evaluated the role of the B-type natriuretic peptides and N-terminal pro-B-type natriuretic peptides in the management of heart failure patients. In a population-based retrospective cohort study of electronic medical records, the thesis examined the patterns of natriuretic peptide testing in primary care practices within the United Kingdom. The thesis showed that single brain natriuretic peptides and N-terminal pro brain natriuretic peptides were independent predictors of all-cause mortality and cardiovascular mortality in the primary care setting. In a small subgroup of patients with two natriuretic peptides measured, changes in brain natriuretic peptides did not provide additional prognostic information beyond a single point-in-time peptide level. Age adversely impacted the mortality especially in elderly. In a clinical trial setting, the thesis also investigated the within-subject variability of B-type natriuretic peptides, vital signs and serum creatinine over a three-month period in stable chronic heart failure patients with New York Heart Association class II-III. Correlations between B-type natriuretic peptides and cardiac structure factors, weight, heart rate, blood pressure and serum creatinine were estimated. The B-type natriuretic peptide within-subject variability was 46%, much higher than the heart rate or blood pressure within-subject variability of 10%, serum creatinine within-subject variability of approximately 8% and weight within-subject variability of 1%. The three-month monitoring interval of B-type natriuretic peptides in stable chronic heart failure was too short. Extended monitoring intervals should be further investigated. Monitoring natriuretic peptides in primary care provides an opportunity to positively impact the burden of heart failure by better directing management for patients with poorer prognoses and better utilizing health care resources.</p

B-type and N-terminal pro-B-type natriuretic peptides in heart failure

The thesis evaluated the role of the B-type natriuretic peptides and N-terminal pro-B-type natriuretic peptides in the management of heart failure patients. In a population-based retrospective cohort study of electronic medical records, the thesis examined the patterns of natriuretic peptide testing in primary care practices within the United Kingdom. The thesis showed that single brain natriuretic peptides and N-terminal pro brain natriuretic peptides were independent predictors of all-cause mortality and cardiovascular mortality in the primary care setting. In a small subgroup of patients with two natriuretic peptides measured, changes in brain natriuretic peptides did not provide additional prognostic information beyond a single point-in-time peptide level. Age adversely impacted the mortality especially in elderly. In a clinical trial setting, the thesis also investigated the within-subject variability of B-type natriuretic peptides, vital signs and serum creatinine over a three-month period in stable chronic heart failure patients with New York Heart Association class II-III. Correlations between B-type natriuretic peptides and cardiac structure factors, weight, heart rate, blood pressure and serum creatinine were estimated. The B-type natriuretic peptide within-subject variability was 46%, much higher than the heart rate or blood pressure within-subject variability of 10%, serum creatinine within-subject variability of approximately 8% and weight within-subject variability of 1%. The three-month monitoring interval of B-type natriuretic peptides in stable chronic heart failure was too short. Extended monitoring intervals should be further investigated. Monitoring natriuretic peptides in primary care provides an opportunity to positively impact the burden of heart failure by better directing management for patients with poorer prognoses and better utilizing health care resources.</p

Reductions in circulating B cell subsets and immunoglobulin G levels with long-term belimumab treatment in patients with SLE

To examine the long-term changes in circulating B cell subsets and IgG levels at 5+ years of continuous belimumab treatment and their correlations with efficacy and safety measures. This was a post hoc analysis of a continuation study (BEL112233; NCT00724867) of eligible US patients who completed the 76-week BLISS-76 Study (BEL110751; NCT00410384), with up to eight calendar-years of follow-up and median (IQR) belimumab exposure of 310 (209, 364) weeks. From week 76, patients initially randomised to intravenous belimumab 1 mg/kg or 10 mg/kg every 4 weeks in BLISS-76 continued to receive the same dose in the continuation study, while those initially randomised to placebo received belimumab 10 mg/kg intravenous every 4 weeks during continuation. All patients continued to receive standard SLE therapy. Biomarker data were collected, and the effects on baseline and early changes (weeks 0-24 after starting belimumab) from baseline in biomarkers on SLE Responder Index (SRI-4) and infection rate were evaluated. Of the 819 patients from BLISS-76, 268 self-selecting patients entered BEL112233. Compared with baseline, B cell subset counts decreased by 40%-99% after 312 weeks (6 years), and serum IgG levels decreased by 28% after 284 weeks. Higher baseline naïve B cell counts were associated with greater SRI-4 response rates (p<0.05), whereas higher baseline SLE subset plasma and short-lived plasma B cell counts were associated with lower SRI-4 response rates (p<0.05). Elevated baseline IgG levels were associated with increased infection rates over the treatment period (p<0.05), and early greater decreases in IgG levels were associated with higher SRI-4 response rates (p<0.05). Belimumab treatment up to 312 weeks (6 years) resulted in substantial decreases in several circulating B cell subsets and IgG levels. Higher baseline naïve B cell counts and IgG levels were associated with improved SRI-4 response and increased infection rates, respectively

Clinical response beyond the systemic lupus erythematosus responder index: Post-hoc analysis of the BLISS-SC study

Objective The Systemic Lupus Erythematosus (SLE) Responder Index (SRI), developed as a primary outcome measure for use in clinical trials, captures improvement in SLE disease activity without concomitant worsening in disease manifestations. This study investigated the relationships between the SRI and clinical/laboratory correlates of SRI response in patients with SLE. Methods This was a post-hoc analysis of the phase III, double-blind, placebo-controlled study of subcutaneous BeLimumab in Subjects with Systemic lupus erythematosus-SubCutaneous (BLISS-SC). Patients were randomised to weekly belimumab 200 mg subcutaneously or placebo, plus standard SLE therapy. Changes from baseline to week 52 in clinical and laboratory parameters were compared among SRI responders and non-responders, irrespective of the treatment received. Results SRI responders (n=475) had significantly better (p7.5mg/day corticosteroids at baseline, significantly more SRI responders had reductions in prednisone dose to ≤7.5 mg/day than non-responders. SRI responders reported lower flare rates and improvements in serological markers and Functional Assessment of Chronic Illness Therapy-Fatigue score than non-responders. Conclusion SRI response is associated with improvements in clinical and laboratory measures, strengthening its value as a clinically meaningful primary endpoint in clinical trials