Association between teriparatide adherence and healthcare utilization and costs in real-world US kyphoplasty/vertebroplasty patients

Summary

The objective of this study was to examine the association between teriparatide adherence and healthcare utilization and costs in real-world US kyphoplasty/vertebroplasty (KV) patients. Among KV patients newly initiating teriparatide, significantly increased pharmacy costs associated with high teriparatide adherence were offset by significantly lower inpatient utilization and medical costs.

Introduction

This study seeks to examine the association between teriparatide adherence and healthcare utilization/costs in real-world US KV patients.

Methods

Identified patients from a large US administrative claims database were aged 50+ with KV from 1/1/2002–12/31/2010 (first observed KV?=?index). Included individuals had 6+ months of pre-index continuous enrollment and no pre-index teriparatide, cancer, or Paget’s disease. Follow-up period for patients initiating teriparatide was ≤36 months post-index. Three teriparatide adherence cohorts were constructed using the proportion of days covered (PDC) during the follow-up period: low (PDC?≤?0.5), medium (PDC >0.5–≤?0.8), and high (PDC >0.8). Repeated KV admissions, any inpatient admission, number of inpatient admissions, and per-patient-per-month (PPPM) inpatient, outpatient, pharmacy, and total costs were compared between cohorts. The associations between teriparatide adherence and healthcare utilization/costs were examined using multivariable regression models, adjusting for patient demographics and clinical characteristics.

Results

Included were 1,568 patients (mean age, 75 years; 82 % female): 403 (26 %) had low adherence, 382 (24 %) medium, and 783 (50 %) high. After multivariable adjustment, high adherence was significantly associated with the lowest PPPM inpatient (low?=?$1,287; medium?=?$1,005; high?=?$678) and outpatient (low?=?$1,464; medium?=?$1,244; high?=?$1,077) medical costs, but with increased pharmacy costs (low?=?$752; medium?=?$1,159; high?=?$1,616; all P?<?0.05), leading to similar total costs (low?=?$3,344; medium?=?$3,376; high?=?$3,351) between cohorts; high adherence was also significantly associated with the lowest odds of repeated KV admission, any inpatient admission, and number of inpatient admissions (all P?<?0.05).

Conclusions

Among KV patients initiating teriparatide, significantly increased pharmacy costs associated with high teriparatide adherence were offset by significantly lower inpatient utilization and medical costs.     

Teriparatide for osteoporosis: importance of the full course

Teriparatide (TPTD) is the only currently available therapeutic agent that increases the formation of new bone tissue and can provide some remediation of the architectural defects in the osteoporotic skeleton. The use of teriparatide clinically is limited to 24 months. We review clinical findings during daily teriparatide treatment over time. Teriparatide appears to increase bone formation more than bone resorption as determined biochemically and histologically. Teriparatide exerts its positive effects on bone formation in two distinct fashions. The first is direct stimulation of bone formation that occurs within active remodeling sites (remodeling-based bone formation) and on surfaces of bone previously inactive (modeling-based bone formation). The second is an increase in the initiation of new remodeling sites. Both processes contribute to the final increase in bone density observed by non-invasive tools such as DXA. Remodeling is the repair process by which skeletal tissue is maintained in a young healthy state, and when stimulated by TPTD is associated with a positive bone balance within each remodeling cavity. It seems likely therefore that this component will contribute to the anti-fracture efficacy of TPTD. Teriparatide reduces the risk of fracture, and this effect appears to increase with longer duration of therapy. The use of novel treatment regimens, including shorter courses, should be held in abeyance until controlled clinical trials are completed to define the relative fracture benefits of such approaches in comparison to the 24-month daily use of the agent. Summary In patients with osteoporosis at high risk for fracture, the full continuous 24-month course with teriparatide results in improved skeletal health and outcomes than shorter time periods.     

Diagnostik und Therapie seminomatöser Hodentumoren

Currently, seminomas account for about 60% of newly diagnosed testicular cancers in Germany, with an increasing trend. In lower tumor stages the main focus is on the avoidance of over therapy. This is of special interest in stage I where radiotherapy, carboplatin monotherapy and surveillance are available therapies as well as in stage IIA/B. Due to high late toxicity, radiotherapy of the retroperitoneal space is obsolete for young patients with clinical stage I and, in its present form, discussed controversially for patients with clinical stage IIA/B. The cause for this paradigm shift is the high percentage of secondary malignancies resulting after radiotherapy of the retroperitoneal space. Furthermore, 10–25% of the patients receiving radiotherapy alone for clinical stage IIA/B seminoma suffer from a relapse of the disease due to tumor recurrence in extraregional lymph nodes. Therefore, an ongoing study is investigating if a combined treatment with neoadjuvant carboplatin and radiotherapy with a limited target volume can reduce toxicity without jeopardizing the cure rate. Patients with residual tumors >3 cm should undergo 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) computed tomography scanning after a minimum interval of 6 weeks after chemotherapy. In the case of a positive FDG-PET-CT result, the further therapeutic strategy should be the subject of interdisciplinary discussions.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen

Using the CD40 system, in vitro proliferation of hairy cell leukemia (HCL) was examined in 43 patients. In this culture system, cells were stimulated by interleukin-4 (IL-4) and anti-CD40 monoclonal antibodies (MoAbs) that were added in soluble form or were cross-linked via their Fc part using Fc gamma RII-transfected mouse fibroblast cells. Proliferation was induced and confirmed by 3H-thymidine incorporation in 14 cases and by the presence of metaphases in 42 cases. 3H-thymidine incorporation showed a heterogeneous pattern: cross-linking of anti- CD40 gave the highest proliferation in 8 cases; in 11 cases, stimulation with anti-CD40 MoAbs alone, without cross-linking also resulted in proliferation; the addition of IL-4 further enhanced 3H- thymidine incorporation in 5 cases, but suppressed this phenomenon in 5 other cases. The CD40 system proved to be very effective in obtaining cytogenetic data. With a success rate of 42 of 43 patients tested, we found clonal abnormalities in 8 cases (19%) and nonclonal abnormalities with involvement of one or two abnormal metaphases in another 7 cases. The chromosomes most frequently involved in the abnormal karyotypes, both structurally and numerically, were chromosomes 5, 7, and 14. By fluorescence-activated cell-sorting analysis of the cultured cells, and by immunophenotypic analysis of metaphase spreads, T-cell growth could be excluded and the HCL-lineage confirmed. Stimulation via the CD40 antigen is an excellent tool for growing hairy cell leukemia cells.     

Inhibition and complexation of activated protein C by two major inhibitors in plasma

To determine the major physiologic inhibitors of activated protein C (APC), plasma was incubated with APC or with Protac C and subjected to immunoblotting. APC:inhibitor complexes gave two major bands reacting with antiprotein C antibodies when immunoblotted on nondenaturing gels, and additional minor bands that varied between serum and plasma. Formation of one of the two major bands of APC:inhibitor complex, but not the other, was stimulated by heparin and only this band reacted with antibodies to the previously described APC inhibitor that is here designated PCI-1. Plasma immunodepleted of PCI-1 formed complexes with APC as visualized with antiprotein C but not anti-PCI-1 antibodies, and exhibited heparin-independent inhibition of APC activity, providing evidence for the existence of a second major physiologic APC inhibitor, PCI-2. Formation of APC:PCI-2 complexes in PCI-1-depleted plasma paralleled inhibition of APC amidolytic activity. PCI-2 was separated from PCI-1 and partially purified using column chromatography. PCI-2 formed inactive complexes of approximately 110,000 molecular weight (mol wt) with APC suggesting PCI-2 has an approximate mol wt of 50,000. Thus, inhibition of APC in plasma involves two major distinct 50,000 mol wt inhibitors, the heparin-dependent PCI-1 and the heparin- independent PCI-2.