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Alemayehu B.,Astrazeneca | Ke X.,Astrazeneca | Youssef N.N.,NPS Pharmaceuticals | Crawley J.A.,Astrazeneca | Levine D.S.,Ironwood Pharmaceuticals
Postgraduate Medicine

Esomeprazole was excluded from the United Healthcare formulary for all commercial health plan members January 1, 2007. A retrospective analysis of the Ingenix LabRx database (September 1, 2005, through June 30, 2007) evaluated the effect of this exclusion on health care utilization and costs in a real-world setting. Total medical care services, including pharmacy claims, were examined for 6 months before and after the esomeprazole exclusion. Patients aged ≥ 18 years were included if they had continuous health plan enrollment (September 1, 2005, through June 30, 2007), ≥ 1 esomeprazole prescription during the index period (March 1 through August 31, 2006), and ≥ 2 esomeprazole prescriptions (with no switch to another proton pump inhibitor [PPI]) during the baseline period (sliding 6-month window from September 1 through August 31, 2006). During the 6-month post-exclusion period (January 1 through June 30, 2007), 19.5% of patients remained on esomeprazole, 43% switched to another PPI, and 37.5% had no prescription PPI claims. Compared with the previous 6 months, post-exclusion was associated with increased health care utilization, including a 4.2% increase in number of inpatient visits, and a 2.7% increase in other services (eg, laboratory testing, ambulatory procedures). Esomeprazole prescriptions decreased by 76.5%, whereas overall pharmacy claims for all drug classes (including gastrointestinal drugs) increased by 5.2%. Six-month prescription drug costs decreased by $177/patient (95% confidence interval [CI], $160-$194/patient), whereas costs for total medical services increased by $450/patient (95% CI, $259-$640/patient), resulting in a net increase of $273/patient (95% CI, $137-$408/patient). Total and gastrointestinal-related medical services costs were significantly higher for those switching to another PPI versus those continuing esomeprazole. Inpatient utilization contributed most (44.5%) to increased costs of nongastrointestinal comorbidities. This study provides real-world evidence that formulary exclusions can lead to unintended increases in overall health care utilization and costs that exceed anticipated pharmacy budget savings. © Postgraduate Medicine. Source

Roepcke S.,Takeda Pharmaceuticals International GmbH | Nave R.,Takeda GmbH | Cyran J.,NPS Pharmaceuticals | Plock N.,Takeda Pharmaceuticals International GmbH | And 2 more authors.
International Journal of Clinical Pharmacology and Therapeutics

Objective: Teduglutide is a recombinant analogue of human glucagon-like peptide-2 (GLP-2) that was recently approved by the US and European regulatory agencies FDA and EMA for the treatment of short bowel syndrome (SBS). The objectives of this work were, firstly, to develop a population pharmacokinetic (popPK) model based on the available PK data of the entire clinical development program and, secondly, to utilize the model for the justification of the proposed dosing regimen. The exploratory analysis was based on a previously established structural PK model and focused primarily on the investigation of covariate effects. Results: The plasma concentration-time profiles of teduglutide after subcutaneous application were adequately described by a 1-compartment model with first order absorption and elimination. The area under the curve (AUC) was lower for male subjects, for subjects with higher creatinine clearance, for overweight subjects, and for SBS patients. However, except for subjects with severe renal impairment no clinically relevant effects on AUC were identified. Conclusion: Our model-based analysis supports the approved dose adjustment for SBS patients with and without renal impairments maintaining the exposure in a value range with acceptable variance for the target population. © 2014 Dustri-Verlag Dr. K. Feistle. Source

Jeppesen P.B.,Rigshospitalet | Messing B.,Hopital Beaujon Service de Gastroenterologie et Assistance Nutritive | Iyer K.,Mount Sinai Medical Center | Seidner D.L.,Vanderbilt University | And 4 more authors.

Background & Aims: Teduglutide, a glucagon-like peptide 2 analogue, might restore intestinal structural and functional integrity by promoting growth of the mucosa and reducing gastric emptying and secretion. These factors could increase fluid and nutrient absorption in patients with short bowel syndrome with intestinal failure (SBS-IF). We performed a prospective study to determine whether teduglutide reduces parenteral support in patients with SBS-IF. Methods: We performed a 24-week study of patients with SBS-IF who were given subcutaneous teduglutide (0.05 mg/kg/d; n = 43) or placebo (n = 43) once daily. Parenteral support was reduced if 48-hour urine volumes exceeded baseline values by <10%. The primary efficacy end point was number of responders (patients with >20% reduction in parenteral support volume from baseline at weeks 20 and 24). Results: There were significantly more responders in the teduglutide group (27/43 [63%]) than the placebo group (13/43 [30%]; P =.002). At week 24, the mean reduction in parenteral support volume in the teduglutide group was 4.4 ± 3.8 L/wk (baseline 12.9 ± 7.8 L/wk) compared with 2.3 ± 2.7 L/wk (baseline 13.2 ± 7.4 L/wk) in the placebo group (P <.001). The percentage of patients with a 1-day or more reduction in the weekly need for parenteral support was greater in the teduglutide group (21/39 [54%]) than in the placebo group (9/39 [23%]; P =.005). Teduglutide increased plasma concentrations of citrulline, a biomarker of mucosal mass. The distribution of treatment-emergent adverse events that led to study discontinuation was similar between patients given teduglutide (n = 2) and placebo (n = 3). Conclusions: Twenty-four weeks of teduglutide treatment was generally well tolerated in patients with SBS-IF. Treatment with teduglutide reduced volumes and numbers of days of parenteral support for patients with SBS-IF; ClinicalTrials.gov Number, NCT00798967. © 2012 AGA Institute. Source

Zanchetta J.R.,Institute Investigaciones Metablicas | Bogado C.E.,Institute Investigaciones Metablicas | Cisari C.,University of Piemonte Orientale | Aslanidis S.,Hippokration General Hospital | And 3 more authors.
Current Medical Research and Opinion

Objective: To determine the safety and efficacy of full-length parathyroid hormone, PTH(184), treatment for up to 36 months by evaluating bone mineral density (BMD) changes, bone histomorphometric indices, and clinical fracture incidence in postmenopausal women with osteoporosis. Background: The TOP trial demonstrated increased lumbar spine BMD (6.9) versus placebo after 18 months of PTH(184) treatment and reduced the incidence of new vertebral fractures (61; p0.001). The therapeutic benefits of long-term treatment of postmenopausal women with PTH(184) are unknown. Methods: The safety and efficacy of 36 months of once-daily dosing with 100g PTH(184) in postmenopausal women with osteoporosis were assessed. Women receiving placebo during the TOP trial were eligible for PTH(184) in the extension study. Clinical trial registration: NCT00172120. Results: Lumbar spine BMD increased by 8.5 above baseline (p<0.001) at 36 months of PTH(184) treatment, remaining stable during the last 12 months of treatment. Increases in total hip and femoral neck BMD occurred more slowly, reaching 3.2 and 3.4, respectively above baseline at 36 months (p<0.001). The total hip BMD showed no signs of reaching a limiting value although the femoral neck plateaued from months 24 to 36. Seven patients had vertebral fractures during the placebo phase of the TOP trial and before entering the extension study, but this rate decreased with the introduction of PTH(184) therapy, resulting in a single worsened vertebral fracture in the first 6 months and no further vertebral fractures from months 6 to 36. Treatment over 36 months with PTH(184) was well-tolerated and iliac crest biopsies showed no adverse effects on bone. Limitations: There was no placebo group for BMD comparisons. The number of patients assessed for fracture incidence was small. Conclusions: PTH(184) treatment for 36 months resulted in significant increases in BMD at the lumbar spine and hip, was associated with a lower incidence of vertebral fracture when compared to before therapy initiation, and was well-tolerated. The continuous increases in total hip BMD suggest that prolonged PTH(184) treatment may be beneficial for postmenopausal osteoporosis. Increased BMD at the femoral neck and lumbar spine also showed favourable changes but plateaued between 24 and 36 months. Long-term treatment was not associated with abnormalities in bone biopsies. © 2010 Informa UK Ltd All rights reserved. Source

Jeppesen P.B.,CA 2121 Rigshospitalet | Pertkiewicz M.,Medical University of Warsaw | Forbes A.,University College London | Pironi L.,University of Bologna | And 7 more authors.
Clinical Nutrition

Background & aims: Short bowel syndrome (SBS)-intestinal failure (IF) patients have impaired quality of life (QoL) and suffer from the burden of malabsorption and parenteral support (PS). A phase III study demonstrated that treatment with teduglutide, a glucagon-like peptide 2 analogue, reduces PS volumes by 32% while maintaining oral fluid intake constant; placebo-treated patients had reduced PS by 21%, but oral fluid intake increased accordingly. As effects of teduglutide on QoL are unknown, they were investigated here. Methods: QoL analyses from a double-blind, randomised Phase III study in 86 SBS-IF patients receiving teduglutide (0.05mg/kg/day s.c.) or placebo over 24 weeks. At baseline and every 4 weeks, QoL was assessed using the validated SBS-QoL™ scale. Results: PS reductions were associated with QoL improvements (ANCOVA, p=0.0194, SBS-QoL per-protocol). Compared to baseline, teduglutide significantly improved the SBS-QoL™ total score and the score of 9 of 17 items at week 24. These changes were not significant compared to placebo. Teduglutide-treated patients with remaining small intestine >100cm experienced more gastrointestinal adverse events (GI-AE), unfavourably affecting QoL. Conclusions: Overall, PS volume reductions were associated with improvements in SBS-QoL™ scores. The short observation period, imbalances in oral fluid intake in relation to PS reductions, large patient and effect heterogeneity and occurrence of GI-AE in a subgroup of teduglutide-treated patients may account for the inability to show statistically significant effects of teduglutide on SBS-QoL™ scores compared to placebo. ClinicalTrials.gov identifier: NCT00798967. © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. Source

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