adjusting for age and preva lent vertebral fracture strata.
EVENITY significantly reduced the incidence of clinical fracture (a composite endpoint of symptomaticvertebral fracture and nonvertebral fracture) at 12 months. However, 88% of these clinical fractures werenonvertebral fractures and the incidence of nonvertebral fractures was not statistically significantlydifferent when comparing EVENITY-treated women to placebo-treated women at month 12 or month 24.
Effect on BMD
EVENITY significantly increased BMD at the lumbar spine, total hip, and femoral neck compared withplacebo at month 12. The treatment differences in BMD were 12.7% at the lumbar spine, 5.8% at the totalhip, and 5.2% at the femoral neck.
Following the transition from EVENITY to denosumab at month 12, BMD continued to increase throughmonth 24. In patients who transitioned from placebo to denosumab, BMD also increased with denosumabuse. The differences in BMD achieved at month 12 between EVENITY and placebo patients were overallmaintained at month 24, when comparing patients who transitioned from EVENITY to denosumab tothose who transitioned from placebo to denosumab. There was no evidence of differences in effects on
BMD at the lumbar spine or total hip across subgroups defined by baseline age, baseline BMD, orgeographic region.
After EVENITY discontinuation, BMD returns to approximately baseline levels within 12 months in theabsence of follow-on antiresorptive therapy [see Indications and Usage (1.2)].
Bone Histology and Histomorphometry
A total of 154 transiliac crest bone biopsy specimens were obtained from 139 postmenopausal womenwith osteoporosis at month 2, month 12, and/or month 24. All of these biopsies were adequate forqualitative histology and 138 (90%) were adequate for full quantitative histomorphometry assessment.
Qualitative histology assessments from women treated with EVENITY showed normal bone architectureand quality at all time points. There was no evidence of woven bone, mineralization defects, or marrowfibrosis.
Histomorphometry assessments on biopsies at months 2 and 12 compared the effect of EVENITY withplacebo (15 specimens at month 2 and 39 specimens at month 12 in the EVENITY group, 14 specimensat month 2 and 31 specimens at month 12 in the placebo group). At month 2 in women treated withEVENITY, histomorphometric indices of bone formation at trabecular and endocortical surfaces wereincreased. These effects on bone formation were accompanied by adecrease in indices of bone resorption.
At month 12, both bone formation and resorption indices were decreased with EVENITY, while bonevolume, and trabecular and cortical thickness were increased.
Study 2 (NCT01631214) was a randomized, double-blind, alendronate-controlled study ofpostmenopausal women aged 55 to 90 years (mean age of 74 years) with BMD T-score less than or equalto −2.5 at the total hip or femoral neck and either one moderate or severe vertebral fracture or two mildvertebral fractures, or BMD T-score less than or equal to -2.0 at the total hip or femoral neck and eithertwo moderate or severe vertebral fractures or a history of a proximal femur fracture. Women were
randomized (1:1) to receive either monthly subcutaneous injections of EVENITY (N = 2046) or oralalendronate 70 mg weekly (N = 2047) for 12 months, with 500 to 1000 mg calcium and 600 to 800international units vitamin D supplementation daily. After the 12-month treatment period, women in botharms tra |
