Malignancies in the rheumatoid arthritis abatacept clinical development programme: an epidemiological assessment.

OBJECTIVE: To provide context for the malignancy experience in the rheumatoid arthritis (RA) abatacept clinical development programme (CDP) by performing comparisons with similar RA patients and the general population. METHODS: Malignancy outcomes included total malignancy (excluding non-melanoma skin cancer (NMSC)), breast, colorectal, lung cancers and lymphoma. Comparisons were made between the observed incidence in patients within the abatacept CDP and RA patients on disease-modifying antirheumatic drugs (DMARD) identified from five data sources: the population-based British Columbia RA Cohort, the Norfolk Arthritis Register, the National Data Bank for Rheumatic Diseases, the Sweden Early RA Register and the General Practice Research Database. Age and sex-adjusted incidence rates (IR) and standardised incidence ratios (SIR) were used to compare events in the abatacept trials with the RA DMARD cohorts and the general population. RESULTS: A total of 4134 RA patients treated with abatacept in seven trials and 41,529 DMARD-treated RA patients in the five observational cohorts was identified for study inclusion. In the abatacept-treated patients, the 51 malignancies (excluding NMSC), seven cases of breast, two cases of colorectal, 13 cases of lung cancer and five cases of lymphoma observed were not greater than the range of expected cases from the five RA cohorts. The SIR comparing RA patients with the general population were consistent with those reported in the literature. CONCLUSIONS: The IR of total malignancy (excluding NMSC), breast, colorectal, lung cancers and lymphoma in the abatacept CDP were consistent with those in a comparable RA population. These data suggest no new safety signals with respect to malignancies, which will continue to be monitored.

Assessment of the association between blood pressure control and health care resource use.

BACKGROUND: Several studies have reported increased health care resource use among hypertensive patients with uncontrolled blood pressure (BP). OBJECTIVE: The purpose of this study was to investigate the relationship between BP control and health care resource use. METHODS: Data were obtained from the Caring for Hypertension on Initiation: Costs and Effectiveness (CHOICE) study, a multicenter feasibility study of actual physician and patient behavior and clinical outcomes in a naturalistic setting. Adult patients with newly diagnosed hypertension were randomized to either Group 1 (treatment with diuretics or beta-blockers) or Group 2 (treatment with calcium channel blockers or angiotensin-converting enzyme inhibitors) and followed for 5 +/- 1 months. Physicians practiced standard care while documenting medications, BP measurements, and health care resource use for their patients. A subsequent analysis evaluating the relationship between BP and physician visits was performed for the whole population and for a subpopulation of patients with at least 4 months of follow-up data. Cox regression was used to model time to next visit. RESULTS: A total of 512 patients with newly diagnosed hypertension were followed: 399 had follow-up data for at least 4 months. Baseline demographic characteristics were similar in the 2 groups. Kaplan-Meier curves and a log-rank test showed that the time to next visit for patients with uncontrolled BP was significantly shorter than for patients whose BP was controlled (P < 0.05). On average, patients with uncontrolled BP (> or = 140/90 mm Hg) had follow-up office visits approximately 13 days earlier than patients with controlled BP (< 140/90 mm Hg). This association remained significant after adjustment for repeated measures, and after exclusion of the first return visit. Cox regression analysis showed that higher systolic and diastolic BP measurements were significantly associated with a shorter time to next visit, after adjustment for age and sex. Total estimated costs during the study period were $170 per patient for medications and $283 per patient for office visits. CONCLUSIONS: In the CHOICE study, higher BP was associated with a shorter time to next visit. Office visits were the main cost driver in the short-term management of hypertension.

Temporal patterns of circulating leptin levels in lean and obese adolescents: relationships to insulin, growth hormone, and free fatty acids rhythmicity.

Alterations in nutritional status, such as obesity, markedly influence insulin, leptin, GH secretion, and free fatty acid (FFA) levels. We measured every hour for 24 h circulating leptin, insulin, GH, and FFA levels in lean and obese adolescents to determine: 1) the impact of adolescent obesity on the diurnal changes in leptin concentrations; and 2) the temporal relationships between the diurnal patterns of circulating leptin levels and insulin, GH, and FFA levels. During puberty, we found that the 24-h profile of circulating plasma leptin levels follows a bimodal pattern with minimal concentrations occurring early in the afternoon and a nocturnal elevation starting after midnight and culminating early morning. The time course of the diurnal variation in leptin levels in the obese adolescents was not different from that in lean controls. Of note, however, in obese girls leptin 24-h excursion and leptin night to day ratio were lower than those found in lean girls. In obese adolescents, mean GH levels varied significantly less during the day and night than lean controls. During the day, there were distinct preprandial increases and postprandial decreases in FFA levels, whereas after midnight FFA levels rose in both lean and obese adolescents. A significant positive correlation was found between mean plasma insulin levels between 0800 h and 2000 h and peak in leptin in lean and obese girls and boys (r = 0.63, P: < 0.001). Peak leptin was inversely correlated with the area under the nocturnal GH levels in all groups (r = -0.31, P: < 0.0003), whereas it was positively correlated with the nocturnal peak in FFA levels (r = 0.45, P: < 0.004). In summary, we report in obese adolescent girls a blunted relative diurnal excursion in leptin levels. This abnormal rhythmicity may, in part, explain their leptin resistance state. The nocturnal rise in leptin was paralleled by a nocturnal rise in GH and FFA levels. Additional studies are needed to test the potential link between the adipose-derived peptide and GH axis in humans.