PowerPoint プレゼンテーション

Journal Club
Benjamin Z Leder, Joy N Tsai, Alexander V Uihlein, Paul M Wallace, Hang Lee, Robert M Neer,
Sherri-Ann M Burnett-Bowie F M Strippoli
Denosumab and teriparatide transitions in postmenopausal
osteoporosis (the DATA-Switch study): extension of a randomised
controlled trial
Lancet July 3, 2015
http://dx.doi.org/10.1016/ S0140-6736(15)61120-5
2015年8月27日 8:30-8:55
８階医局
埼玉医科大学総合医療センター内分泌・糖尿病内科
Department of Endocrinology and Diabetes,
Saitama Medical Center, Saitama Medical University
Sellami Mnif Houda
Denosumab
プラリア皮下注(第一三共) 抗RANKLモノクローナ
ル抗体６カ月に１回皮下投与する。薬価は60mg１
mL１筒 29,296円
2013年６月11日
沈降炭酸カルシウム、コレカルシフェ
デノタスチュアブル配合錠
Teriparatide
ロール（天然型ビタミンD）及び炭酸マ
グネシウムを含有する経口剤
１日１回２錠
20.9円
テリパラチド（商品名：フォルテオ皮下注カート
600μg、同皮下注キット600μg リリー）
1日1回20μgを皮下注する（投与は24カ月まで）
600㎍キット 53,353円１回分 1905.5円
2010年7月23日
Teriparatide
テリボン（旭化成ファーマ、主成分テリパラチド 56.5μg
瓶 = 13,342円）
1週間に1回通院をして注射 72週間まで
2011年11月25日
Lancet 2013; 382: 50–56
12 months study
J Clin Endocrinol Metab, May 2014, 99(5):1694–1700
24 months study
Introduction
No approved therapy is able to restore skeletal integrity in most
osteoporotic patients
Long-term use of osteoporosis drugs is controversial
two or more therapies
Combined teriparatide and denosumab.
Continuously increased
bone mineral density more
than either drug alone
Discontinuously treatment
results in rapidly declining
bone mineral density
OBJECTIVE:
To assess the changes in bone mineral density in postmenopausal
osteoporotic women who transitioned between treatments.
METHOD:
Randomised controlled trial (DATA-Switch) : preplanned extension of the
denosumab and teriparatide administration study (DATA)
94
postmenopausal osteoporotic women randomly assigned to receive 24
months of teriparatide (20 mg daily), denosumab (60 mg every 6
months), or both drugs.
DATA-Switch:
Switch Teriparatide group
Denosumab group
Denosumab group
Teriparatide
Group receiving both received an additional 24 months of Denosumab
alone (combination to denosumab group).
•Bone mineral density (spine, hip, and wrist ) and biochemical markers of
bone turnover : measured at 6 , 12 ,18 and 24 months after the drug
transitions
•Primary endpoint : the percent change in posterior-anterior spine bone
mineral density over 4 years.
• Secondary endpoints: the percent change in total hip, femoral neck, and
radius shaft bone mineral density and the percent change in serum
osteocalcin and C-telopeptide concentrations.
In women switching from teriparatide to denosumab, mean (SD) lumbar spine bone mineral
density continued to increase resulting in 48-month increases of 18·3%
RESULTS:
In women switching from combination therapy to denosumab, the net 48-month increase in
bone mineral density was 16·0%
p=0·0005
No significant
differences between the
groups increase
p=0·0203)
Bone mineral density increased more after
the treatment transition in the teriparatide to
denosumab group (24-48 Months)
net 0–48-month
decrease of –1·8%
The 0–48month bone
mineral density
increases in the
combination to
denosumab G
were signifi
cantly larger
than those
either in the
teriparatide to
denosumab
group
(p=0·0075) or
the denosumab
to teriparatide
group
(p=0·0099).
-(0-48 Months) Increased more in the comb to
8·6%
denosumab group than in either the
teriparatide /denosumab G (p=0·0446) or the
denosumab to teriparatide G (p<0·0001)
9·1%
8·3%
4·9%
-Increase in Teri/Deno was better than
Deno/Teri (p=0·0002)
6·6%
decreased
( 24 -36
months
before)
then
increase
( 36- 42
months)
Increases by
275%
Increases by
183%
40 pc above
baseline
159%
Bone formation (Osteocal) was
not suppressed until 12–24
months of denosumab treatment
both markers were maximally
suppressed at all post-switch
timepoints
Teri G has significantly higher level p <0.0001, and p<0.0023 (Moths 25-30)
Bone resorption (C-telopeptide) was
maximally suppressed after 1 month of
denosumab
Significant hypercalcaemia (blood calcium >10·8 mg/dL confi
rmed on repeat testing) : identified in one patient during
months 24–48 (denosumab to teriparatide group).
Serious adverse events reported in six participants in the
teriparatide to denosumab group (ductal carcinoma in situ
of the breast, syncope, chronic obstructive pulmonary
disease exacerbation, elective cervical laminectomy,
fundoplication procedure, and non-ST elevation myocardial
infarction
4 participants in the denosumab to teriparatide group
(appendicitis, laryngitis or pharyngitis, nephrolithiasis
without hypercalcaemia, and anaemia due to a gastric ulcer),
and three participants in the combination to denosumab
group (breast cancer, atrial fi brillation, and atrial fi brillation
with stroke)
Possibly related to TTT
(teriparatide
In postmenopausal osteoporosis, switching therapy from
teriparatide to denosumab further increases bone mineral
density at all measured sites, whereas switching therapy
from denosumab to teriparatide results in transient bone loss
at the hip and spine and progressive bone loss at the radius
shaft.
Additionally, we have shown that 24 months of combined
therapy followed by 24 months of denosumab alone is
associated with largest cumulative bone mineral density
increases at the hip and radius, increases that are greater
than have been reported with any currently available therapy
taken for a similar duration.
the importance of the order of anabolic versus antiresorptive
therapy with denosumab. The bone loss that occurs in patients
switching from denosumab to teriparatide was an unexpected
finding
IN CONCLUSION
In postmenopausal osteoporosis, the order in which
denosumab and teriparatide are used has a significant effect
on overall treatment effectiveness.
Specifically, teriparatide does not adequately prevent
bone loss after denosumab, whereas denosumab stabilises
and further increases bone mineral density when used after
teriparatide or combination therapy.
The largest increases in bone mineral density at the hip
and wrist, and the largest bone mineral density increases
possible in any clinical context, are achieved in women treated
with 24 months of combined teriparatide plus denosumab
followed by 24 months of denosumab monotherapy.
These should the approach to the initial and sequential
treatment of osteoporotic women, particularly those with
established disease who are at an acutely high risk of fragility
fracture
Three important points can be derived from the DATA-Switch
study:
first, when embarking on sequential monotherapy, a course
of teriparatide followed by denosumab translates into a
sustained increase of BMD;
second, combination therapy with teriparatide and
denosumab leads to the greatest BMD gain compared with
individual therapy when followed by denosumab;
and third, denosumab followed by teriparatide monotherapy
should be avoided as it results in a transient loss of BMD at
the spine and the hip and progressive loss of BMD at the
distal radius (see figure 3 in Leder and colleagues’ paper).
*Lorenz C Hofbauer, Tilman D Rachner
Division of Endocrinology, Diabetes, and Bone Diseases, Technische Universität Dresden Medical Center,
01307 Dresden, Germany (LCH, TDR); and Center for Regenerative Therapies Dresden, Germany (LCH)
www.thelancet.com Published online July 3, 2015 http://dx.doi.org/10.1016/S0140-6736(15)61175-8
Message
DATA試験に参加した閉経後骨粗鬆症患者77人を
対象に、治療薬の切り替えに伴う骨密度の変化
を無作為化比較試験で検証（DATA-Switch試験）。
48カ月時の脊椎の平均骨密度増加率はテリパラ
チドからデノスマブ群18.3％、デノスマブから
テリパラチド群14.0％、併用からデノスマブ群
16.0％だった。
http://www.m3.com/clinical/journal/15630

Download Report