Pharmacy & Therapeutics - November 2008 - (Page 670)

MEETING HIGHLIGHTS: ESMO and ASBMR spine or total hip T-scores of between –2.8 and –4, and 23% had prior fractures. Women were randomly assigned to receive subcutaneous (SQ) injections of denosumab 60 mg every six months or placebo. All patients were also taking 400 International Units (IU) of oral vitamin D and 1 g of elemental calcium daily. After 36 months, women receiving denosumab had a 68% decreased incidence of new vertebral fractures, as confirmed by radiography, compared with women receiving placebo. The reduction was 61% in the first year, increasing to 78% in the second year, and leveling off to 75% in the third year. The incidence of fractures with placebo was 7.2%; with denosumab, the fracture incidence was reduced to 2.3%. After three years, nonvertebral fractures were also reduced by 20% in the denosumab group, compared with the placebo group. Hip fractures were decreased by 40%. Dr. Cummings pointed out that the reduced fracture incidence correlated with robust increases in bone mineral density (BMD), including a 9.2% increase in BMD at the lumbar spine and a 6% increase in the hip. Lower fracture risk was also correlated with reductions in biochemical markers of bone turnover, most notably a 72% reduction in serum C-terminal telopeptide after three years. “Given the strength of the effects on bone density and resorption, I expected to see a strong decrease in fractures. It was what I expected and hoped for,” Dr. Cummings said. Dr. Cummings also noted a statistically significant reduction in self-reported falls among the denosumab-treated patients. He acknowledged, however, that such reports are difficult to interpret because patients may be more likely to record and report a fall if there was a consequent fracture. Adverse events were generally similar with denosumab and placebo. Roughly 25% of patients in both groups reported serious adverse effects, with infections at a rate of just over 50% in both groups. Life-threatening adverse events (stroke, cardiac events, atrial fibrillation, and malignancy) were rare in both groups (range, 1%–2%). Dr. Cummings concluded that twice-yearly injections of denosumab 60 mg resulted in major reductions in the incidence of fractures in this high-risk population. efficacy in building BMD. At 24 months, patients taking the 50-mg dose showed a mean increase in BMD of 5.48% over baseline at the lumbar spine. Women receiving placebo showed a 0.19% decrease in BMD. Total hip BMD increased by 3.16%, compared with –0.93% for placebo. Femoral neck BMD increased by 3.84%, compared with –0.85% for placebo. Decreases in BMD were noted at all three sites with the lowest dose of odanacatib (3 mg). The 50-mg weekly odanacatib dose resulted in a mean 51% decrease in urinary N-telopeptide (uNTx), and a 30.6% reduction in serum C-telopeptide (sCTx), two key markers of bone resorption. In the placebo-treated patients, sCTx increased by 32.8%; Ntx decreased, but only by 4.6%. However, odanacatib 50 mg did produce 13% to 20% increases in markers of new bone formation—in bone-specific alkaline phosphatase (s-BASP) and in serum N-terminal propeptides of type-1 collagen (sP1NP). Rates of adverse events with odanacatib were similar to those with placebo, with 35% of the women treated with 50 mg reporting adverse effects versus 39.8% of those receiving placebo. Discontinuation rates were 7.7% for those receiving odanacatib 50 mg and 4.8% for those receiving placebo. Nausea, rash, headache, and muscle spasms were the most common odanacatib-associated adverse events. Dr. McClung mentioned that a large global phase 3 trial is under way to determine whether the changes in BMD and bone turnover found with odanacatib will translate into a reduced incidence of fractures. I COMING SOON TO P&T EDITORIAL: Evidence-Informed Case Rates David B. Nash, MD, MBA DRUG FORECAST: Tetrabenazine (Xenazine): An FDA-Approved Treatment Option for Huntington’s Disease– Related Chorea Tatiana Yero, PharmD, CPS, and Jose A. Rey, PharmD, BCPP FEATURE ARTICLE: Interpreting Estimates of Treatment Effects: Implications for Managed Care Stephen V. Faraone, PhD CONTINUING EDUCATION CREDIT: Classification and Pharmacological Management Of Obesity Sarah R. Erlanger, PharmD, and Emily A. Henson, PharmD Odanacatib: Building New Bone • Michael McClung, MD, Director, Oregon Osteoporosis Center, Portland, Ore. Odanacatib (MK-0822, Merck) is a first-in-class selective inhibitor of cathepsin-K, an enzyme that plays a key role in osteoclastic degradation of the protein content of bone. In a multicenter study involving 399 postmenopausal women with a baseline BMD in the range of –2.0 to –3.5, odanacatib produced dose-dependent increases in BMD. The women were treated for two years with weekly oral odanacatib at doses of 3, 10, 25, or 50 mg. They also took 5,600 IU of supplemental vitamin D each week. Subjects with an average daily calcium intake under 1,000 mg were also given calcium carbonate 500 mg/day. At doses of 10, 25, and 50 mg, weekly odanacatib produced significant increases in lumbar, total hip, and femoral neck BMD. Not surprisingly, the 50-mg dose showed the greatest 670 P&T® • November 2008 • Vol. 33 No. 11

Table of Contents Feed for the Digital Edition of Pharmacy & Therapeutics - November 2008

Pharmacy & Therapeutics - November 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Heparin-Induced Thrombocytopenia Medication Utilization Patterns and Hypertension-Related Expenditures among Patients Who Were Switched From Fixed-Dose to Free-Combination Antihypertensive Therapy European Society for Medical Oncology and Association for the Study of Bone and Mineral Research Pharmaceutical Approval Update

Pharmacy & Therapeutics - November 2008

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