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Osteoporose
1. Empfehlungen
2. Hilfsmittel
3. Ausblick
4. Anmeldung STZ
Absolutes Frakturrisiko mit Frax
Limitationen Frax
• Vorbehandelte Patienten
• Wirbelfrakturen
• Verlauf
Unterschiedliche Scores
Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial
Tsai J.N. et al. Lancet published online May 15, 2013
DATA-Studie: Denosumab und Teriparatid in Mono- oder Kombinationstherapie bei postmenopausaler Osteoporose
Design Offene, randomisierte, kontrollierte Studie 12 Monate Behandlung
Patienten 94 postmenopausale Frauen mit hohem Frakturrisiko (mittleres Alter: 66 Jahre)
Behandlung Entweder die Kombination Teriparatid 20ug täglich plus Denosumab 60mg alle 6 Monate oder jeweils mit einer der beiden Einzelnsubstanz allein im Verhältnis 1:1:1
Ausschluss-kriterien
• Vortherapie mit oralen BPs in den letzten 6 Monaten
• Vortherapie mit i.v. BPs oder Strontiumranelat
Endpunkte Prozentuale Änderung der DXA-BMD an der Gesamthüfte, Schenkelhals, LWS und 1/3 Radius nach 12 Monaten
Methodik:
Tsai et al. Lancet 2013
Tsai et al. Lancet 2013
Kombinierte Behandlung mit Denosumab und Teriparatid:die DATA-Studie > Änderungen der Knochenmineraldichte
Ergebnisse: Effekt auf Knochendichte nach 12 Monate
**
*
*
Ergebnisse:
BMD-Entwicklung nach 12 Monaten an der Lendenwirbelsäule
Kombinierte Behandlung mit Denosumab und Teriparatid:die DATA-Studie > Änderungen der Knochenmineraldichte
p-Wert
Dmab vs TPTD n.s.
Kombi vs TPTD 0,0005
Kombi vs Dmab < 0,0001
Kombination
TeriparatidDenosumab
Monate
LWS
BM
D-Ä
nd
eru
ng
(%
)
12600
2
4
6
8
10
Tsai et al. Lancet 2013
Ergebnisse:
BMD-Entwicklung nach 12 Monaten an der Hüfte
Kombinierte Behandlung mit Denosumab und Teriparatid:die DATA-Studie > Änderungen der Knochenmineraldichte
p-Wert
Dmab vs TPTD 0,003
Kombi vs TPTD < 0,0001
Kombi vs Dmab 0,0001
p-Wert
Dmab vs TPTD n.s.
Kombi vs TPTD < 0,001
Kombi vs Dmab 0,013
Kombination
Denosumab
TeriparatidBM
D-Ä
nd
eru
ng
(%
)
Monate
Schenkelhals
12600
1
2
3
6
4
5 Kombination
Denosumab
TeriparatidBM
D-Ä
nd
eru
ng
(%
)Monate
Gesamthüfte6
5
4
3
1
2
00 6 12
Tsai et al. Lancet 2013
DATA-Studie: Denosumab und Teriparatid in Mono- oder Kombinationstherapie bei postmenopausaler Osteoporose
Fazit:
Die Kombinationstherapie mit Teriparatid plus Denosumab erhöhte
die Knochendichte stärker als die jeweiligen Monotherapien an allen
gemessenen Stellen
Autoren suggerieren, dass diese Kombinationstherapie zu einem
additiven Effekt auf beide kortikalen und trabekulären Knochen führte
Diese Kombination könnte die Osteoporose-Behandlung bei
Patientinnen mit hohem Frakturrisiko verbessern
Tsai et al. Lancet 2013
International, multicenter, open-label, single-arm study
Key Inclusion Criteria: Completed the Pivotal Phase 3 Fracture Trial (completed their 3-year visit, did not discontinue
investigational product, and did not miss more than 1 dose). Not receiving any other osteoporosis medications.
Study DesignThe Pivotal Phase 3 Study – Extension
Pivotal Phase 3 Fracture Trial Extension Study
1 2 3Year 0 5 6 74 8 9 10
1 2 30 5 6 74Year
RANDOMIZATION
Denosumab 60 mgSC Q6M
(N = 3,902)
PlaceboSC Q6M
(N = 3,906)
ContinuedDenosumabTreatment
Cross-overDenosumabTreatment
Denosumab 60 mgSC Q6M
(N = 2,343)
Denosumab 60 mgSC Q6M
(N = 2,207)
Calcium and Vitamin D
SC = subcutaneous; Q6M = once every six monthsAdapted from Brown JP, et al. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL.
Change in Lumbar Spine and Total Hip BMD Through 6 Years with Denosumab Treatment
The Pivotal Phase 3 Study – Extension
Data represents LS means and 95% CI. n = number of subjects with values at baseline and the time point of interest. *P < 0.05 vs Pivotal Phase 3 Study baseline; †P < 0.0001 vs Pivotal Phase 3 Study baseline and Extension baseline. ‡Represents subjects from the Pivotal Phase 3 Study DXA substudy. Orange numbers on the graphs represent the percent change in BMD while on denosumab treatment.
BMD = bone mineral density; CI = confidence interval; LS = least-squares; DXA = dual-emission X-ray absorptiometry Adapted from: Brown JP, et al. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL.Cummings SR, et al. N Engl J Med. 2009;361:756-765.
2005 1485119‡ 122‡ 120‡ 122‡ 2028 1923Cross-over n 1962 1456118‡ 120‡ 2023 1998 2007 18962112 1588139‡ 141‡ 141‡ 142‡ 2148 2040Continued n 2086 1565139‡ 140‡ 2149 2125 2134 2016
Placebo Continued DenosumabCross-over Denosumab
Lumbar Spine BMD
*
–2
0
2
4
6
8
10
12
14
16
18
†
*
*
*
*
*
15.2%
Pe
rce
nt
Ch
an
ge
Fro
m B
as
eli
ne
1 2 3 4 50 6Study Year
†
†
†
†
†10.1% 9.4%
Pivotal Phase 3 Fracture Trial
ExtensionStudy
Total Hip BMD
*
–2
0
2
4
6
8
10
*
*
*
Study Year1 2 3 4 50 6
*
*
*
*
*
7.5%
†
††
†
†
†
5.7%
4.8%
Pivotal Phase 3 Fracture Trial
ExtensionStudy
Yearly Incidence of New Vertebral Fractures Through 6 Years
The Pivotal Phase 3 Study – Extension
n = number of patients with ≥1 fracture. N = number of randomized patients who remained on study at the beginning of each period and had available spine x-rays during the period of interest. *Annualized rate: (2-year rate)/2. Lateral radiographs (lumbar and thoracic) were not obtained at year 4 (year 1 of the Extension).
Adapted from: Brown JP, et al. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL.Data on file, Amgen.
Yea
rly
Inci
den
ce o
f N
ew
Ver
teb
ral
Fra
ctu
re (
%)
Years of Denosumab Exposure
Fracture incidence was not evaluated as an efficacy endpoint in the extension study
Pivotal Phase 3 Fracture Trial Extension Study
Placebo Continued Denosumab Cross-over Denosumab
1898 35107 2482n 32 58 23341,6103,186 3,2473,400 3,4533,691N 3,702 2,101 1,5091,980
Yearly Incidence of Nonvertebral Fractures Through 6 Years
The Pivotal Phase 3 Study – Extension
n = number of patients with ≥ 1 fracture. N = of randomized patients who remained on study at the beginning of each period.Percentages for nonvertebral fractures are Kaplan-Meier estimates.Adapted from: Brown JP, et al. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL.Data on file, Amgen.
Yea
rly
Inci
den
ce o
fN
on
vert
ebra
l F
ract
ure
(%
)
Years of Denosumab Exposure
Fracture incidence was not evaluated as an efficacy endpoint in the extension study
Pivotal Phase 3 Fracture Trial Extension Study
2,2433,454 3,4873,688 3,6823,906N 3,902 2,343 2,1052,207 2,0661,9642683 73103 75116n 98 32 3652 2429
Placebo Continued Denosumab Cross-over Denosumab
Neue Studien
Ernährung und Exercise: Do-Health, Frau Prof H.BischoffGeriatrie, ZAM, Senioren >70Medikamente: Anti-Sclerostin, Resultate in 2-3 Jahren,
Therapie:Therapiepause, Monitoring