Reasons to switch to Prolia®

Reasons to initiate a switch

SWITCH

INADEQUATE RESPONSE TO

THERAPY

POOR PERSISTENCE/ADHERENCE

PATIENT PREFERENCE/

CHOICE

INTOLERANCE

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As shown by 3 key studies, switching to Prolia® significantly increases BMD* at key sites vs. oral BPs1–3

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BMD: bone mineral density; BP: bisphosphonate.1. Kendler DL et al. J Bone Miner Res 2010; 25: 72–81.2. Recknor C et al. Obstet Gynecol 2013; 121: 1291–1299.3. Roux C et al. Bone 2014; 58: 48–54.

*BMD data results from these trials should not be extrapolated to predict differences in fracture efficacy. Head-to-head fracture studies have not been conducted.

Studies that measured % change in BMD* from baseline at the hip and other key sites

STAND:Patients who switched from oral alendronate to Prolia® vs. those who remained on oral alendronate1

Transition to ibandronate:Patients with prior suboptimal oral BP use who switched to Prolia® vs. those who switched to oral ibandronate2

Transition to risedronate:Patients with prior suboptimal daily or weekly oral alendronate use who switched to Prolia® vs. those who switched to oral risedronate3

As shown by 3 key studies, switching to Prolia® significantly increases BMD* at the total hip vs. oral BPs1–3

BMD: bone mineral density; BP: bisphosphonate; TTI: transition to ibandronate; TTR: transition to risedronate.1. Kendler DL et al. J Bone Miner Res 2010; 25: 72–81.2. Recknor C et al. Obstet Gynecol 2013; 121: 1291–1299.3. Roux C et al. Bone 2014; 58: 48–54.

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*BMD data results from these trials should not be extrapolated to predict differences in fracture efficacy. Head-to-head fracture studies have not been conducted.

As shown by 3 key studies, switching to Prolia® significantly increases BMD* at the lumbar spine vs. oral BPs1–3

BMD: bone mineral density; BP: bisphosphonate; TTI: transition to ibandronate; TTR: transition to risedronate.1. Kendler DL et al. J Bone Miner Res 2010; 25: 72–81.2. Recknor C et al. Obstet Gynecol 2013; 121: 1291–1299.3. Roux C et al. Bone 2014; 58: 48–54.

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*BMD data results from these trials should not be extrapolated to predict differences in fracture efficacy. Head-to-head fracture studies have not been conducted.

As shown by 3 key studies, switching to Prolia® significantly increases BMD* at the femoral neck vs. oral BPs1–3

BMD: bone mineral density; BP: bisphosphonate; TTI: transition to ibandronate; TTR: transition to risedronate.1. Kendler DL et al. J Bone Miner Res 2010; 25: 72–81.2. Recknor C et al. Obstet Gynecol 2013; 121: 1291–1299.3. Roux C et al. Bone 2014; 58: 48–54.4. Kendler DL et al. Osteoporos Int 2009; 20(Suppl. 2): S191–S229.

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*BMD data results from these trials should not be extrapolated to predict differences in fracture efficacy. Head-to-head fracture studies have not been conducted.

“Drug Holiday”

骨密度穩定、未曾發生骨折、且屬骨折低危險發生之患者，在已使用雙磷酸鹽藥物(靜脈注射劑型滿三年，口服劑型滿五年後)，宜評估繼續用藥之效益，是否持續用藥

2017 TOA Guideline

Managing special populations

Prolia® reduces the risk of hip fractures by 62%* in patients aged ≥75 years1

RRR: relative risk reduction.1. Boonen S et al. J Clin Endocrinol Metab 2011; 96: 1727–1736.

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Republished with permission of J Clin Endocrinol Metab, from Treatment with Denosumab Reduces the Incidence of New Vertebral and Hip Fractures in Postmenopausal Women at High Risk, Boonen S et al. 96: 1727–1736, © 2011; permission conveyed through Copyright Clearance Center, Inc.The absolute risk reduction for Prolia® vs. placebo was 1.4% for hip fractures.1*Prolia® provided a relative hip fracture risk reduction of 62% [P=0.007] at 36 months in patients 75 to 90 years. This reduction was significant as early as 12 months after Prolia® was initiated. In patients younger than 75 years, the incidence of hip fractures was quite low in both treatment groups. The treatment-by-age interaction was not significant (P=0.07).1

Prolia® ensures a robust and consistently low incidence of hip fractures in patients aged ≥75 years over the course of 6 years1

1. Papapoulos S et al. Long-term Denosumab Treatment Maintains Low Incidence of Fracture in Postmenopausal Women ≥75 Years With Osteoporosis. ASBMR 2012 (abstract).

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n: number of subjects randomised in FREEDOM or enrolled in the FREEDOM Extension study. Percentages for hip fractures are Kaplan-Meier estimates.1

Prolia® ensures a robust and consistently low incidence of new vertebral fractures in patients aged ≥75 years over the course of 6 years1

45 1. Papapoulos S et al. Long-term Denosumab Treatment Maintains Low Incidence of Fracture in Postmenopausal Women ≥75 Years With Osteoporosis. ASBMR 2012 (abstract).

n: number of subjects randomised in FREEDOM or enrolled in the FREEDOM Extension study. Fracture incidence is based on crude incidence rate.1

Prolia® ensures a robust and consistently low incidence of non-vertebral fractures in patients aged ≥75 years over the course of 6 years1,2

1. Papapoulos S et al. Long-term Denosumab Treatment Maintains Low Incidence of Fracture in Postmenopausal Women ≥75 Years With Osteoporosis. ASBMR 2012 (abstract);

2. Cummings SR et al. N Engl J Med 2009; 361: 756–765.46

n: number of subjects randomised in FREEDOM or enrolled in the FREEDOM Extension study. Percentages for non-vertebral fractures are Kaplan-Meier estimates.1*All non-vertebral fractures. Fractures of the skull, face, mandible, metacarpals, fingers or toes were excluded because they are not associated with decreased bone mineral density. Pathological fractures and those associated with severe trauma were also excluded.2

Prolia® reduced incidence of fractures in patients with chronic kidney disease1

• The interaction terms were not statistically significant, indicating no difference in the effect of Prolia® by level of renal function

47 CrCl: creatinine clearance.1. Jamal SA et al. J Bone Miner Res 2011; 26: 1829–1835.

N: number of randomised subjects with an evaluation during the time period of interest.There were no subjects with a CrCl < 15 mL/min; *P<0.05.

Stage of chronic kidney disease does not affect the frequency of adverse events with Prolia® 1

STAGE 4 CKD STAGE 3 CKD STAGE 2 CKD STAGE 1 CKD

PlaceboN=37

Prolia®

N=36PlaceboN=1,392

Prolia®

N=1,410PlaceboN=2,034

Prolia®

N=2,015PlaceboN=410

Prolia®

N=423

Adverse events, n (%)

35 (94.6)

35 (97.2)

1,307 (93.9)

1,308 (92.8)

1,875 (92.2)

1,869 (92.8)

387 (94.4)

391 (92.4)

Serious adverse events, n (%)

13 (35.1)

15 (41.7)

351 (25.2)

392 (27.8)

509(25.0)

502 (25.0)

99 (24.1)

95 (22.5)

Serious adverse events of infection, n (%)

1 (2.7)

4 (11.1)

49 (3.5)

60 (4.3)

66 (3.2)

79 (3.9)

17 (4.1)

16(3.8)

Cardiovascular serious adverse events, n (%)

3 (8.1)

4 (11.1)

88 (6.3)

88 (6.3)

71 (3.5)

78 (3.9)

16 (3.9)

16 (3.8)

48 CKD:chronic kidney disease.1. Jamal SA et al. J Bone Miner Res 2011; 26: 1829–1835.

PROLIA® Administration

Prolia保骼麗

●全新機轉，100%全人類單株抗體●6個月一針皮下注射，使用方便●不經肝腎代謝，不傷肝腎●十年臨床試驗證實效果及安全性●搭配骨鬆照護計劃，全方位照顧病人

Prolia®: One 60 mg subcutaneous injection every 6 months1..\..\Denosumab (Prolia) - YouTube (360p).mp4

52 1. Prolia® (denosumab), Summary of Product Characteristics, July 2015.2. Prolia® Patient Information Leaflet (PIL), 2013.

• Prolia® can be administered at any time of the day, regardless of meals, every 6 months1

Denosumab (Prolia) -

YouTube (360p).mp4

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• Prolia® can be administered at any time of the day, regardless of meals, every 6 months1

1. Prolia® (denosumab), Summary of Product Characteristics, July 2015.2. Prolia® Patient Information Leaflet (PIL), 2013.

Prolia®: One 60 mg subcutaneous injection every 6 months1

Considerations for patients who are elderly or have comorbid conditions1,2

• No dose adjustment is required in elderly patients1老人不用調劑量

• No dose adjustment is required in patients with renal impairment1– Patients with severe renal impairment (creatinine clearance <30 ml/min)

are at greater risk of developing hypocalcaemia. Clinical monitoring of calcium levels is recommended for patients predisposed to hypocalcaemia1腎功能不好不用調整

• Prolia® pharmacokinetics are not expected to be affected by hepatic impairment1肝功能不好不用調整

• Prolia® may be administered at any time of the day, regardless of meals, every 6 months1隨時可打

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Refer to Prolia® Summary of Product Characteristics for the full safety precautions for use.11. Prolia® (denosumab), Summary of Product Characteristics, July 2015.

健保給付標準＄＄

•健保價: 6,122/每六個月皮下注射一次•Fosamax Plus (202*26= 5,252 ); Aclasta 5,458, Evista38.3*365/2=6,990

•限用於停經後婦女、骨質疏鬆症男性患者。•一次限用一項藥物，不得併用其他骨鬆治療藥物

• Prolia 無需監測病患腎功能

骨質疏鬆症（DEXA檢測 T score＜ -2.5）引起脊椎或髖部骨折

骨質疏少症（DEXA檢測-2.5＜T ＜ -1.0）引起脊椎或髖部2處或2次(含)以上骨折

Prolia® prescribing information保骼麗™注射液Prolia® (denosumab) 衛署菌疫輸字第000918號

適應症 : 治療有骨折高風險之停經後婦女骨質疏鬆症。治療有高度骨折風險之骨質疏鬆症男性患者，以增加骨量(bone mass)。治療因為非轉移性攝護腺癌而進行雄性賀爾蒙抑制治療且具高度骨折風險之男性患者的骨質流失現象。

建議劑量 : Prolia的建議劑量為每6個月一次皮下注射單劑60毫克。請以皮下注射的方式將Prolia施打於上臂、大腿或腹部。所有的患者都應每天補充1000毫克的鈣質與至少400 IU的維生素D。如果漏打一劑Prolia，應於患者方便時儘快施打，之後再從最後一次注射的日期算起，排定每6個月一次的注射時間。

禁忌 : 低血鈣症：在開始使用Prolia治療之前，必須先矯治既有的低血鈣症。懷孕：對孕婦投與Prolia可能會造成胎兒傷害。Prolia禁用於已懷孕的婦女。如果患者在懷孕期間使用本藥，或在使用本藥期間懷孕，應告知患者胎兒可能面臨的風險。過敏：Prolia禁用於曾對本品之任何成份發生全身性過敏反應的患者。這些反應包括全身性過敏反應(anaphylaxis)、臉部腫脹與蕁麻疹。

警語和注意事項: 1. 含有相同活性成份的藥品：接受Prolia治療的患者不可使用Xgeva。2. 過敏：使用Prolia曾有發生臨床上明顯過敏反應的報告，包括全身性過敏反應(anaphylaxis)。3. 嚴重感染：併用免疫抑制劑或免疫系統受損的患者發生嚴重感染的風險可能會升高。4. 低血鈣症與礦物質代謝：低血鈣症可能會因使用Prolia而惡化。治療之前，必須先矯治既有的低血鈣症。對嚴重腎功能受損或正在接受透析治療的患者，施打後發生低血鈣症是一個相當重大的風險。請告知嚴重腎功能受損的患者(包括正在接受透析治療的患者）低血鈣症的症狀，以及適量補充鈣質與維生素D以維持血鈣濃度的重要性。5. 皮膚不良反應：大型臨床試驗中，表皮與皮膚方面的不良事件，如皮膚炎、濕疹與皮疹，在Prolia組中的發生率明顯高於安慰劑組。如果出現嚴重的症狀，應考慮停用Prolia。6. 顎骨壞死：顎骨壞死(ONJ)會自然發生，且通常和拔牙及(或)局部感染後癒合延遲有關。對併有發生ONJ之危險因子的患者，在開始使用Prolia治療之前，應考慮進行牙科檢查並採取適當的口腔預防措施。使用Prolia治療期間應維持良好的口腔衛生習慣。7. 非典型股骨粗隆下骨折與骨幹骨折。8. 對骨代謝的抑制作用。9. 腎功能損害：對腎功能受損的患者，並不須調整劑量。對嚴重腎功能受損或正在接受透析治療的患者投予Prolia時，應權衡其效益風險概況。10. 肝功能損害：目前尚無任何臨床研究評估過肝功能損害對Prolia之藥物動力學的影響。

不良反應 : 使用Prolia時最常通報的不良反應為背痛、四肢疼痛、肌肉骨骼疼痛、高膽固醇血症、以及膀胱炎。使用Prolia治療骨質疏鬆症男性患者時，最常通報的不良反應為背痛、關節痛以及鼻咽炎。使用Prolia治療因攝護腺癌而進行雄性荷爾蒙抑制治療之男性患者，或因乳癌而進行芳香酶抑制劑輔助治療之女性患者所引起的骨質流失現象時，最常通報的不良反應為關節痛和背痛。

產品相關資訊可諮詢 MedInfo.JAPAc@amgen.com 或 0080 1611 483；產品相關不良反應，請通報 Safety-Taiwan@amgen.com 或 0080 1611 483。

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