ARCOXIAARCOXIA®®

For Optimal Pain managementFor Optimal Pain management

光田醫院光田醫院光田醫院光田醫院 神經外科神經外科神經外科神經外科 程久俊程久俊程久俊程久俊 主任主任主任主任

ContentContent• Burden of Disease

• Product Profiles Chemical structure/Mechanism/Pharmacokinetics

• GI Tolerability

• Efficacy

– OA, RA, AS, Acute Gout

• NSAIDs comparison

• CV Safety :

MEDAL Program

• Conclusion

• Prescription Information

Long-standing troubles with your muscles, bones and joints (rheumatism, arthritis)

Hypertension (high blood pressure)

Allergy

Migraine or frequent headaches

Chronic anxiety or depression

Asthma

22%

19%

17%

16%

9%

7%

Health in the European Union SurveyHealth in the European Union Survey

Asthma

Diabetes

Chronic bronchitis, emphysema

Osteoporosis

Cataract

Peptic ulcer (gastric or duodenal ulcer)

Cancer

Stroke, cerebral haemorrhage

7%

6%

5%

5%

4%

4%

2%

2%

N = 25,031

Health in the European Union Report, 2007. Available at: http://ec.europa.eu/public_opinion/archives/ebs/ebs_272e_en.pdfQuestion : Do you have, or have you ever had, any of the following health problems? 7

Pain in Europe Survey: OA Was a Leading Cause of Chronic Pain 1Pain in Europe Survey: OA Was a Leading Cause of Chronic Pain 1

Arthritis/OA

Herniated discs

The Pain in Europe survey, the largest survey of chronic pain sufferers in Europe(N>46,000), reported that arthritis/OA was the most common cause of chronic pain

15

34

1. Pain in Europe: a report. www.britishpainsociety.org/Pain%20in%20Europ%20survey%20report.pdf. Accessed 8-March-2011.

Rheumatoid arthritis

Traumatic injury

Migraine headaches

Prevalence, %

7

8

12

0 10 20 30 40

OA=osteoarthritis.

General Stress ResponseGeneral Stress Response

Endocrine/Metabolic• ↑ ACTH, cortisol,

catecholamines, interleukin-1

• ↓ insulin

AcutePain

• Physiology response • Psychology response

• ↓ insulin

Water/Electrolyte Flux• ↑ H2O, Na+ retention

ACTH = adrenocorticotropic hormoneKehlet H. Reg Anesth.1996;21(6S):35–37.Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.

Anxiety

Depression

Sleep deprivation

•4-times more likely

to have

anxiety/depression

(p<0.001)

•Twice as likely to

have difficulty in

work

OARSI Guidelines Recommended Medications* for OA Pain 1OARSI Guidelines Recommended Medications* for OA Pain 1

Acetaminophen

NSAIDs

COX-2 Inhibitors

Opioids (weak and strong)

*Recommended oral, non–disease modifying analgesics.OARSI=Osteoarthritis Research Society International; OA=osteoarthritis; NSAIDs=nonsteroidal anti-inflammatory drugs; COX-2=cyclooxygenase-2.1. Zhang W et al. Osteoarthritis Cartilage. 2008;16:137–162.

Product Profile Product Profile

9

The meaning of ARCOXIAThe meaning of ARCOXIA

ARCOXIAArthritis Analgesia

Etoricoxib

928’ Tab/ Box

Mechanism of Action of NSAIDsMechanism of Action of NSAIDs

NSAIDsCOXCOX--11 COXCOX--22

Arachidonic acid

CO2

X X

COXCOX--2 inhibitor2 inhibitor

NSAID = nonsteroidal anti-inflammatory drugAdapted from Wallace JL Am J Med 1999;107(suppl 6A):11S–17S; Vane JR et al Annu Rev Pharmacol Toxicol 1998;38:97–120; Fung HG et al Clin Ther 1999;21:1131–1157.

NSAIDs

Protection of gastric mucosa

Hemostasis

COXCOX--11“Constitutive”“Constitutive”

COXCOX--22“Inducible”“Inducible”

Pain andfever Inflammation

Kidney

X

ProstaglandinsProstaglandins

X

11

胃黏膜保護作用 發炎,疼痛 ,發燒

Etoricoxib Pharmacokinetics: Absorption and t1/2aEtoricoxib Pharmacokinetics: Absorption and t1/2a

24 minutes onset24 hours duration

非磺胺類藥物

aSingle oral doses to healthy subjects.t1/2=half-life.Adapted from Agrawal NGB, et al. J Clin Pharmacol.2003;43(3):268–276.

Adapted from Friesen RW, et al. Bioorg Med Chem Lett.1998;8(19):2777–2782; Penning TD, et al. J Med Chem. 1997;40(9):1347–1365; Riendeau D, et al. J Pharmacol Exp Ther. 2001;296(2):558–566.

1小時達最高血中濃度，半衰期22小時

Tmax and t1/2Tmax and t1/2

Tmax (hour) t 1/2 (hour)

ARCOXIA 1 22Celecoxib 2–3 8–12

Diclofenac 1–5.25 2

Ibuprofen 0.75–1.5 2 Once daily dosingMeloxicam 4–5 20

Naproxen 2–4 12–17

Indomethacin 2 4.5

Nimesulide 2–3 2–5

dosing

Tmax = time to maximum plasma concentration t1/2 = half-life*Single oral doses to healthy subjectsAdapted from Agrawal NGB et al J Clin Pharmacol 2003;43:268–276. 15

GI TolerabilityGI TolerabilityGI TolerabilityGI Tolerability

Cum

ulat

ive

inci

denc

e

0.04

0.06Etoricoxib ≥60 mg (n=3142)Nonselective NSAIDs combined** (n=1828)

p<0.001

~55%Riskreduction

GI Tolerability ProfileGI Tolerability ProfileEtoricoxib vs. Nonselective NSAIDs: GI PUBsEtoricoxib vs. Nonselective NSAIDs: GI PUBs

EtoricoxibEtoricoxib had lower incidence of confirmed PUBs in the clinical had lower incidence of confirmed PUBs in the clinic al development program*development program*

NSAIDs = nonsteroidal anti-inflammatory drugs; PUBs = perforations, ulcers, bleeds *Combined analysis of 10 clinical trials in OA, RA, and chronic low back pain; **Naproxen 1000 mg/day, ibuprofen 2400 mg/day, or diclofenac 150 mg/dayAdapted from Hunt RH et al Am J Gastroenterol 2003;98:1725–1733; Curtis S et al. Poster presented at EULAR, 2002.

Cum

ulat

ive

inci

denc

e

Days (active treatment period)0 90 180 270 360 540

0.02

0.00

p<0.001reduction

450

EfficacyEfficacyOsteoarthritisRheumatoid Arthritis Rheumatoid Arthritis Ankylosing Spondylitis

Acute Gouty ArthritisPostoperative pain

Osteoarthritis

Etoricoxib vs. Diclofenac :WOMAC Pain Subscale*

Osteoarthritis

Etoricoxib vs. Diclofenac :WOMAC Pain Subscale*

Mea

n ch

ange

from

bas

elin

e in

Morepain

Etoricoxib 60 mg once daily (n=253)Diclofenac 50 mg three times daily (n=258)–10

0

–5

–15

Etoricoxib provided effective and sustained pain re lief similar Etoricoxib provided effective and sustained pain re lief similar to diclofenacto diclofenac

Mea

n ch

ange

from

bas

elin

e in

pa

in le

vel (

mm

)

2 4 6S

Lesspain

R

NSAIDwashoutperiod

Weeks postrandomization

–40

–30

–20

–25

–35

*0- to 100-mm VAS (0 = no pain to 100 = extreme pain )Adapted from Zacher J et al Curr Med Res Opin 2003;19(8):725–736.

Osteoarthritis

Etoricoxib vs. Diclofenac : PGARTa at 4 Hours b (Day 1)

Osteoarthritis

Etoricoxib vs. Diclofenac : PGARTa at 4 Hours b (Day 1)

Etoricoxib 60 mg(n=187)

23 31 30 214

Etoricoxib therapy resulted in significantly more p atients with good Etoricoxib therapy resulted in significantly more p atients with good or excellent responses vs. initial dose of diclofen acor excellent responses vs. initial dose of diclofen ac

% Patients

Diclofenac 50 mgd

(n=199)

None Poor Fair Good Excellent

15 24 42 18 1

a0- to 4-point Likert scale ( 0 = excellent to 4 = no ne); bfour hours ±±±± 15 minutes after the first dose (morning); cp=0.007 for etoricoxib 60 mg vs. diclofenac 50 mg for good or excellent response s; dInitial dose

Adapted from Zacher J et al Curr Med Res Opin 2003;19(8):725–736.

32

19

27

Osteoarthritis

Etoricoxib 30 mg vs Celecoxib 200mg (Phase 3): WOMAC Pain Subscalea

Osteoarthritis

Etoricoxib 30 mg vs Celecoxib 200mg (Phase 3): WOMAC Pain Subscalea

SE

, mm

–10

0

–5

Study 1

Etoricoxib relieved pain in both clinical studiesEtoricoxib relieved pain in both clinical studies

0

–5

Study 2

Morepain

Etoricoxib 30 mg (n=228)

Celecoxib 200 mg (n=236)

Placebo (n=126)

Etoricoxib 30 mg (n=243)

Celecoxib 200 mg (n=246)

Placebo (n=112)

P<0.001 active treatment vs placebo P<0.001 active treatment vs placebo

aPain subscale change from flare visit (LS means) me asured on a 0 (none) to 100 (extreme) mm VAS.LS=least-squares; SE=standard error; NS=not signifi cant.Adapted from Bingham CO III, et al. Rheumatology (Oxford). 2007;46(3):496–507.

LS M

ean

Cha

nge

±S

E,

S

Weeks Postrandomization

–30

–20

–10

–15

–25

–35

R 2 4 8 12 16 26 Time-weighted average

over12 weeks

S

–30

–20

–10

–15

–25

–35

R 2 4 8 12 16 26

Lesspain

Weeks Postrandomization

Time-weighted average

over26 weeks

Time-weighted average

over12 weeks

Time-weighted average

over26 weeks

P=NS between active treatments P=NS between active treatments

Objective: To estimate the prevalence of inadequate pain relief (IPR) among patients with symptomatic knee OA prescribed analgesic therapy and to characterize patients with IPR.

Rheumatology (Oxford). 2014 Aug 23.

N =1187

54% of patients met the definition of IPR54% of patients met the definition of IPR

• IPR patients are at high dissatisfaction to treatment- Lack of Efficacy

• Over 1/3 of them are dissatisfied to tolerability of medication- Poor tolerance

• Satisfaction to Medication • SORT result

54%

IPR Non-IPR

Rheumatology (Oxford). 2014 Aug 23.

tolerability of medication- Poor tolerance

IPR predictorsIPR predictors• IPR is associated with

– Functional loss– Impaired QoL

• Practitioners should actively evaluate pain management and the effectiveness of treatment response

• IPR predictors include • IPR predictors include – Female– Higher BMI– Longer OA duration– Bilateral knee OA– Depression – Diabetes

Rheumatology (Oxford). 2014 Aug 23.

An open, single-arm, prospective, observational study in patients with OA

POWER study:Patient-Reported Outcomes With Etoricoxib in Real Life

POWER study:Patient-Reported Outcomes With Etoricoxib in Real Life

Multicenter500 OA patients from 16 sitesDec. 2007 ~ Nov. 2008

Primary Endpoint :the proportion of patients achieving ≥30% decrease from baseline in pain intensity as measured by WOMAC “pain walking on a flat surface”

Existing TreatmentNot satisfied

Etoricoxib 60 mg once daily

Screen 4

Weeks of treatment

- 4

Efficacy

QoL

Dec. 2007 ~ Nov. 2008

80

70

60

5052%

70 %

% of responderN=274

N=204

N=167

Primary endpoint Primary endpoint

Patient with pain VAS ≥ 40 mm rated by investigator

Treat with ARCOXIA for 4 weeks:- 70% of patients improved on pain score- 52% of patients achieved significant improvement (≥30% improvement)

Q1- During the last 48 hours, rate how much pain have you experienced when walking on flat surface on WOMAC pain VAS scale: 0=no pain ~ 100= extreme pain

50

40

30

20

10

0

≥0% ≥30% ≥40% ≥50%

52%43%

36%

N=167N=140

% of VAS reduction

Investigator’s Global Assessment of Response to Therapy (IGART)Investigator’s Global Assessment of Response to Therapy (IGART)

70.00%

60.00%

50.00%

Baseline (n=500)Week 4 (n=430)* P<0.0557.6%

P<0.05

Significant improvement through IGART assessment after switching to ARCOXIA treatment for 4 weeks

50.00%

40.00%

30.00%

20.00%

10.00%

0.00%

4.4%

None Poor Fair Good Excellent

5.8%

16.1%

36.4%

35.4%

1.6%

36.7%

6.1%

Trend test - Mantel-Maenszel Test

2% 43%

Endpoint Baseline Week 4n (%) n (%)

GI protective agent use 101 (20.2) 48 (9.6)Proton pump inhibitor 4 (0.8) 1 (0.2)

H2-antagonist 9 (1.8) 3 (0.6)

GI SafetyGI SafetyAfter switching to etoricoxib,• Substantial decreases in the use of GI-protective agent &

GI nuisance symptoms

H2-antagonist 9 (1.8) 3 (0.6)Antacids 88 (17.6) 44 (8.8)

GI nuisance symptoms 144 (27.6) 27 (5.4)Constipation 54 (10.8) 4 (0.8)

Diarrhea 31 (6.2) 1 (0.2)Heartburn/abdominal pain 19 (3.8) 8 (1.6)

Dyspepsia/distension 12 (2.4) 6 (1.2)Gastritis 9 (1.8) 0 (0.0)

Stomatitis 7 (1.4) 0 (0.0)Nausea 6 (1.2) 6 (1.2)

Vomiting 3 (0.6) 2 (0.4)Dysphasia 3 (0.6) 0 (0.0)

Rheumatoid Arthritis

Patient Preferences for Improved HealthRheumatoid Arthritis

Patient Preferences for Improved Health

Pain

Walking and Bending

Household Tasks

Mobility

Hand and Finger Function

33.3%33.3%

25.1%25.1%

23.9%23.9%

44.6%44.6%

68.6%68.6%

n = 1,024 n = 1,024 RARA patientspatients

00 2020 4040 6060 8080

Mood

Social Activity

Self-care

Work

Arm Function

Responders (%)

18.5%18.5%

13.2%13.2%

17.3%17.3%

9.0%9.0%

11.9%11.9%

n = 1,024 n = 1,024 RARA patientspatients

Heiberg et alHeiberg et al. Arthritis Rheum. . Arthritis Rheum. 2002;47:3912002;47:391--77..

Rheumatoid Arthritis

Etoricoxib vs. Naproxen : Tender-Joint Count

Rheumatoid Arthritis

Etoricoxib vs. Naproxen : Tender-Joint Count

Mea

n ch

ange

from

ba

selin

e (±

SE

)

–10

5

0

–5

–10

0

–5

5International (n=878)US (n=805)

b

SE = standard erroraInvestigator assessment, total 68 each; bp=0.005 for naproxen vs. placebo; cp<0.001 for etoricoxib vs. placebo; dp<0.001 for etoricoxib vs. naproxen; ep<0.001 for both etoricoxib and naproxen vs. placeb o; fp=0.779 for etoricoxib vs. naproxen; g500 mg twice daily

Adapted from Matsumoto AK et al J Rheumatol 2002;29:1623–1630; Collantes E et al BMC Fam Pract 2002;3(1):10.

Mea

n ch

ange

from

ba

selin

e (

Weeks in study

–20

–15

Placebo Etoricoxib 90 mg Naproxen 1000 mg g

(n=315 US, n=349 Int) (n=321 US, n=351 Int) (n=169 U S, n=178 Int)

S R 8 12

–20

–15

2 4

e,f

Improvedresponse

S R 8 12

Weeks in study2 4

b

c,d

US (n=805) International (n=878)5

0

–5

Mea

n ch

ange

from

ba

selin

e (±

SE

)

5

0

–5

Rheumatoid Arthritis

Etoricoxib vs. Naproxen : Swollen-Joint Count

Rheumatoid Arthritis

Etoricoxib vs. Naproxen : Swollen-Joint Count

aInvestigator assessment, total 66 each; bp=0.007 for naproxen vs. placebo; cp<0.001 for etoricoxib vs. placebo; dp=0.030 for etoricoxib vs. naproxen; ep=0.005 for etoricoxib vs. placebo; fp=0.024 for naproxen vs. placebo; gp=0.955 for etoricoxib vs. naproxen; h500 mg twice daily

Adapted from Matsumoto AK et al J Rheumatol 2002;29:1623–1630; Collantes E et al BMC Fam Pract 2002;3(1):10.

S R 8 12

–10

2 4

–15Mea

n ch

ange

from

ba

selin

e (

Weeks in study Weeks in study

S R 8 12

–10

2 4

–15

b

c,de–g

Placebo Etoricoxib 90 mg Naproxen 1000 mg h

(n=315 US, n=349 Int) (n=321 US, n=351 Int) (n=169 US, n=178 Int)

Improvedresponse

Ankylosing Spondylitis

Etoricoxib vs. Naproxen: Patient Assessment of Spine Pain (Parts I and II)

Ankylosing Spondylitis

Etoricoxib vs. Naproxen: Patient Assessment of Spine Pain (Parts I and II)

–20

–10

0

LS m

ean

chan

ge fr

omS

E)

Part I Part II

Placebo(n=93)

Etoricoxib 90 mg(n=126)

Etoricoxib 120 mg(n=123)

Naproxen 1000 mg d

(n=125)

–50

–40

–30

Weeks in studyS

LS m

ean

chan

ge fr

omba

selin

e (±± ±±

SE

)

2 8 34 52

b,c

a0- to 100-mm VAS (0 = none to 100 = severe); bp<0.050, etoricoxib 90 mg vs. naproxen; cp<0.010 etoricoxib, 120 mg vs. naproxen; d500 mg twice dailyAdapted from van der Heijde D et al Arthritis Rheum 2005;52:1205–1215.

R 16 432664

LS m

ean

chan

ge fr

om

±S

E)

Etoricoxib produced substantial improvement vs. bas eline at 4 hoursEtoricoxib produced substantial improvement vs. bas eline at 4 hours

–1.0

0.0

–0.5

–1.5

Acute Gouty Arthritis

Etoricoxib vs. Indomethacin : Patient Assessment of Pain

Acute Gouty Arthritis

Etoricoxib vs. Indomethacin : Patient Assessment of Pain

Study 1 b,c

–1.0

0.0

–0.5

–1.5

Study 2 d,e

LS = least squares; SE = standard error; R = random ization; CI = confidence intervala0- to 4-point Likert scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = extreme); bLS mean change from baseline four hours after initi al dose = –0.94; 95% CI, –1.11, –0.76; cLS mean difference from indomethacin = 0.09 (–0.14, 0.33) over days 2 to 8; dLS mean change from baseline four hours after initial dose = –1.04, 95% CI, –1.2 2, –0.86; eLS mean difference from indomethacin = –0.07 (–0.27 , 0.14); f50 mg three times dailyAdapted from Schumacher HR Jr et al BMJ 2002;324:1488–1492; Rubin BR et al Arthritis Rheum 2004;50:598–606.

LS m

ean

chan

ge fr

om

base

line

(±

R 5

–2.0

–3.02 64 hr 3 4 6 7 8

Day in study

–2.5

R 5

–2.0

–3.02 64 hr 3 4 6 7 8

–2.5

Day in study

Etoricoxib 120 mg (n=72 study 1, n=101 study 2)

Indomethacin 150 mg f

(n=71 study 1, n=83 study 2)

Clin Rheumatol (2016) 35:151–158

• A total of 165 records obtained from the initial search– 86 from EMBASE, – 5 from Cochrane Library, – 13 from PubMed MEDLINE, – 44 from Web of Science, – 16 from China Biology Medicine disc– 1 identified from other sources– 1 identified from other sources

• All studies were selected strictly according to the criteria de scribed.

• 25 studies remained for the full-text review. – 19 studies were ultimately excluded because they are not related to

acute gout or the control group did– After 41 duplicates, 73 reviews, 11 conference papers, 4 case reports,

4 short surveys, 4 notes, and 3 editorials were removed.

Patient-assessed pain for 2–5 days follow-upPatient-assessed pain for 2–5 days follow-up

Clin Rheumatol (2016) 35:151–158

Efficacy for 2–5 days follow-upEfficacy for 2–5 days follow-up

• Efficacy -meta-analysis

• No significant difference between the two interventions

Clin Rheumatol (2016) 35:151–158

GI side effects and dizzinessGI side effects and dizziness

Clin Rheumatol (2016) 35:151–158

DiscussionDiscussion

• Acute gouty arthritis is the most common form of inflammatory joint disease. The primary symptom of acute gout is pain.

• Optimal therapy is directed at controlling inflammation and analgesia . – NSAIDs are considered to be the most potent NSAID for the treatment of gout . – Etoricoxib, has anti- inflammatory,analgesic, and an tipyretic activities in models of acute

or chronic pain and inflammation in osteoarthritis, ankylosing spondylitis, and rheumatoid arthritis . arthritis .

• The first quantitative comparative meta-analysis of studies directly comparing etoricoxib and NSAIDs for the treatment of acute gout. – Ultimately, six RCTs were included, – A systematic review and meta-analysis were performed to replicate and confirm the results of

the studies. – In order to assess the efficacy and safety of etoricoxib, we extracted relative data as much as

possible, and we pooled the outcome whenever possible.

ConclusionConclusion

From this meta-analysis, we found that etoricoxib has similar anti-inflammatory and analgesic effects as indometacin in the treatment of acute gout. Furthermore ,etoricoxib has a significantly lower risk of AEs Furthermore ,etoricoxib has a significantly lower risk of AEs thanindometacin. Etoricoxib 120 mg administered orally once dailymay be effective for the treatment of acute gouty arthritis

Clin Rheumatol (2016) 35:151–158

NSAIDs ComparisonNSAIDs Comparison

Lancet 2017; 390: e21–33

• Estimates of the treatment effects on pain for different daily doses of NSAIDs and paracetamol compared with placebo

Lancet 2017; 390: e21–33

• Estimates of the treatment effects on physical function for different daily doses of NSAIDs and paracetamol compared with placebo

Lancet 2017; 390: e21–33

• Median rank , probability of reaching MID, and SUCRA values of competing interventions and daily doses

• MID=minumum clinically • MID=minumum clinically important difference. SUCRA=surface under the cumulative ranking curve. CrI=credibility interval. *Maximum daily dose.

Lancet 2017; 390: e21–33

Choosing the best NSAID for Central SensitizationChoosing the best NSAID for Central Sensitization

• Etoricoxib crosses the blood brain barrier

12 adult patients received 120 mg etoricoxib (n=8) or placebo (n=4) on day 1 postsurgery.Samples from plasma, CSF, and tissue exudates were collected over a period of 24 h post-dosing and analyzed for etoricoxib and prostaglandin E2 (PGE2) using liquid chromatography-tandem mass spectrometry andimmuno-assay techniques.

Renner B. Naunyn-Schmied Arch Pharmacol (2010) 381:127..

blood brain barrier when used in standard clinical doses

• It might thus prevent the development of central sensitization .

ARCOXIA可通過血腦屏障

CSF concentrations exceeding the median inhibitoryconcentration for COX-2 were achieved by rofecoxib a nd valdecoxibbut not celecoxib.

•Celebrex Does Not Pass•Celebrex Does Not PassBlood- Brain Barrier

Choosing the best NSAID for Central Sensitization

Ibuprofen

Diclofenac

COX2 is a potential target to prevent Central sensitization

Blood Brain Barrier

ARCOXIA

Celebrex

Choosing the best NSAID for IPRChoosing the best NSAID for IPR

Adherence Safety

Efficacy Prevent C sensitization

ARCOIXA

ARCOXIA:一天一次，速效,強效,長效止痛ARCOXIA:一天一次，速效,強效,長效止痛

Cardiovascular SafetyCardiovascular SafetyCardiovascular SafetyCardiovascular Safety

50

MEDAL Program: Cumulative Incidence of Confirmed Thrombotic CV Events (PP)MEDAL Program: Cumulative Incidence of Confirmed Thrombotic CV Events (PP)

Cum

ulat

ive

Inci

denc

e,

Etoricoxib 60 and 90 mg pooled (320 events)Diclofenac 150 mg (323 events)

7

6

5

4

Etoricoxib vs diclofenacHR=0.95 (95% CI: 0.81, 1.11)

Primary Endpoint血栓性心血管事件發生比例兩組相當

CV = cardiovascular; PP = per protocol; CI = confidence interval; HR = hazard ratio

Adapted from Cannon CP et al. Lancet. 2006; in press.

Cum

ulat

ive

Inci

denc

e,

% (

95%

CI)

Months

0 6 4224

0

Patients at riskEtoricoxib 16,819 13,359 10,733 8277 6427 4024 805Diclofenac 16,483 12,800 10,142 7901 6213 3832 815

12 18 30 36

3

2

1P=0.496

58

3.02.8

1.61.4

1.82.02.22.42.6

MEDAL Program: Confirmed Upper GI PUB (mITT)MEDAL Program: Confirmed Upper GI PUB (mITT)

Cum

ulat

ive

Inci

denc

e, Etoricoxib 60 and 90 mg pooled (176 events)Diclofenac 150 mg (246 events)

Etoricoxib vs diclofenacHR=0.69 (95% CI: 0.57, 0.83)

上腸胃道事件Arcoxia發生比例明顯較低

0

1.00.8

0.40.2

0.6

1.41.2

GI = gastrointestinal; PUB = perforation, symptomatic ulcer, bleeds; mITT = modified intention-to-treat; CI = confidence interval; HR = hazard ratioAdapted from Cannon CP et al. Lancet. 2006; in press.

Cum

ulat

ive

Inci

denc

e,

% (

95%

CI)

0

Patients at riskEtoricoxib 17,412 13,704 10,972 8400 6509 4063 821Diclofenac 17,289 13,190 10,396 8027 6306 3867 820

6 422412 18 30 36

Months

P<0.001

61

ConclusionConclusionConclusionConclusion• Among all COX-2 inhibitors ，，，，etoricoxib is

� Fast Onset : 24 mins

� Long duration : 24 hrs

� Once daily , Better compliance

• Etoricoxib’s structure doesn’t have sulfonamide , wi ll not cause sulfonamide

allergy.

• In Treatment Therapy , etoricoxib has equal or better efficacy in treating• In Treatment Therapy , etoricoxib has equal or better efficacy in treating

OA,RA,AS, Acute Gout comparing with standard dose of diclofenac, naproxen,

indomethacin .

• Etoricox can decrease 55% GI PUBs than tNSAIDS

• In MEDAL Program ，，，，Comparing with the most used tNSAIDs diclofenac,

etoricoxib has similar thrombotic CV event rate; but lower upper GI side

effects rate (perforation, bleeding, obstruction, ulcer)

64

適應症及用法用量適應症及用法用量ARCOXIA為口服用藥。ARCOXIA可與食物併服，亦可不與食物併服。ARCOXIA的治療療程應儘可能縮短並使用最低的有效日劑量。

• 骨關節炎– 建議劑量為每日一次30毫克或60毫克。

• 類風濕性關節炎– 建議劑量為每日一次60毫克或90毫克。最低有效每日劑量為60毫克。

• 僵直性脊椎炎– 建議劑量為每日一次60毫克或90毫克。最低有效每日劑量為60毫克。– 建議劑量為每日一次60毫克或90毫克。最低有效每日劑量為60毫克。

• 急性痛風性關節炎– 建議劑量為每日一次120毫克。– ARCOXIA 120毫克應僅用於急性症狀期，治療時間不可超過八天。

• 原發性經痛– 建議劑量為每日一次120毫克。– ARCOXIA 120毫克應僅用於急性症狀期，治療時間不可超過八天。

• 牙科手術後疼痛– 建議劑量為每日一次90毫克；最高劑量不得超過每日一次90毫克。最多可使用3天。

• 婦科手術後疼痛– 建議劑量為每日一次90毫克。起始劑量應於手術前先給藥。最高劑量不得超過每日一次120毫克。最多可使用5天。

健保給付規範健保給付規範1.1.5.非類固醇抗發炎劑（NSAIDs）藥品（如 celecoxib、nabumetone、meloxicam、etodolac、nimesulide）(90/7/1、97/9/1) etoricoxib (96/1/1、99/10/1)、含naproxen及esomeprazole複方製劑(101/10/1)

1.本類製劑之使用需符合下列條件之一者(99/10/1)：(1)年齡大於等於六十歲之骨關節炎病患。(2)類風濕性關節炎、僵直性脊髓炎、乾癬性關節炎等慢性病發炎性關節病變，需長期使用非類固醇抗發炎劑者。(3)合併有急性嚴重創傷、急性中風及急性心血管事件者 (97/2/1)。(3)合併有急性嚴重創傷、急性中風及急性心血管事件者 (97/2/1)。(4)同時併有腎上腺類固醇之患者。(5)曾有消化性潰瘍、上消化道出血或胃穿孔病史者。(6)同時併有抗擬血劑者。(7)肝硬化患者。

2.使用本類製劑之病患不得預防性併用乙型組織胺受體阻斷劑、氫離子幫浦阻斷劑及其他消化性潰瘍用藥，亦不得合併使用前列腺素劑（如misoprostol）3. Nimesulide限用於急性疼痛緩解，其連續處方不得超過15日(97/9/1)。4.含naproxen及esomeprazole複方製劑不得作為急性疼痛的初始治療。(101/10/1)

安全性資訊摘要安全性資訊摘要安全性資訊摘要安全性資訊摘要安全性資訊摘要安全性資訊摘要安全性資訊摘要安全性資訊摘要• 禁忌症

• ARCOXIA禁用的患者：• 對本品之任何成分過敏。

• 充血性心衰竭(NYHA II-IV) 。• 已知患有缺血性心臟疾病、週邊動脈疾病和/或腦血管疾病(包括最近做過冠狀動脈繞道手術或血管修復手術)。進行冠狀動脈繞道手術(Coronary artery

bypass graft, CABG) 之後14天內禁用本藥。• 血壓持續高於140/90 mmHg且無法有效控制之高血壓病人。•

• 注意事項

• 與安慰劑及某些NSAIDs(naproxen)比較，COX-2選擇性抑制劑類藥物可能與增加栓塞事件(尤其是心肌梗塞和中風)的危險性有關。因為COX-2選擇性抑制劑的使用劑量與時間可能會增加心血管的危險性，應儘可能以最短時間與最低有效每日劑量治療。

• 由於COX-2選擇性抑制劑對血小板並不具有作用，因此不可以此類藥物取代阿斯匹靈用於預防心血管疾病。由於etoricoxib(此類藥物的一種)並不會抑制血小板凝集作用，因此不可停止抗血小板療法。

• 有些使用ARCOXIA的病患曾出現體液滯留、水腫和高血壓的現象。特別是在高劑量時，服用etoricoxib可能比其他NSAIDs和COX-2選擇性抑制劑使用者，較常發生高血壓也較嚴重。

• 警語：

• 冠狀動脈繞道手術(CABG)後：• 兩項大型臨床試驗研究顯示，於冠狀動脈繞道手術後10-14天內使用COX-2選擇性抑制劑藥品，其發生心肌梗塞及中風的情形增加。因此，進行冠狀動脈繞道手術之後14天內禁用本藥。

•

• 副作用

• 下列藥物相關不良反應曾見於針對OA、RA或慢性下背痛病患治療達12週之臨床研究的報告中。在以ARCOXIA治療之病患所發生的不良反應中，發生率≥1%且高於安慰劑者包括：虛弱無力/疲倦、眩暈、下肢水腫、高血壓、消化不良、胃灼熱、噁心、頭痛、ALT升高、AST升高。

• 其他仿單內容，處方前，請詳閱藥品仿單及說明書。

Thanks for your AttentionThanks for your AttentionThanks for your AttentionThanks for your Attention

MUSC-1236936-0000

Q & AQ & AQ & AQ & A

肝功能不全肝功能不全肝功能不全肝功能不全肝功能不全肝功能不全肝功能不全肝功能不全

ARCOXIA Celecoxib

肝功能不全對輕度肝功能不全的患者(Child-Pugh分數為5-6)，不可使用超過每日一次60毫克的劑量。對中度肝功能不全的患者(Child-Pugh分數為7-9)，應降低劑量；不可使用超過每隔一日60毫克的劑量。對嚴重肝功

中度肝功能不全: 每日建議做大劑量需降低50%嚴重肝功能不全病人不建議使用

超過每隔一日60毫克的劑量。對嚴重肝功能不全的患者(Child-Pugh分數>9)，目前並無任何臨床或藥物動力學方面的相關資料(見注意事項)。

腎功能不全腎功能不全腎功能不全腎功能不全腎功能不全腎功能不全腎功能不全腎功能不全

ARCOXIA Celecoxib

腎功能不全對後期腎病患者(肌酸酐廓清率<30 mL/min)，並不建議使用ARCOXIA治療。對腎功能不全程度較輕的患者(肌酸酐廓清率>30 mL/min)，無須調整其劑量(見注意事項)。

與其他NSAID相似，不建議重度腎功能不全病人使用

意事項)。

高血壓高血壓高血壓高血壓高血壓高血壓高血壓高血壓

ARCOXIA Celecoxib

禁忌症血壓持續高於140/90 mmHg且無法有效控制之高血壓病人。有些使用ARCOXIA的病患曾出現體液滯留、水腫和高血壓的現象。對先前曾有水腫現象、高血壓、或心臟衰竭的病患，在使用

Celebrex和其他所有NSAID一樣，可能導致新的高血壓發病或使原有的高血壓惡化，進而促使心血管事件的發生率增加高血壓病人影謹慎使用NSAIDs，包括Ｃelebrex在內療程中應該密切監測血壓象、高血壓、或心臟衰竭的病患，在使用

ARCOXIA時，應考慮發生體液滯留、水腫或高血壓的可能性。

療程中應該密切監測血壓

水腫水腫水腫水腫/充血性心衰竭充血性心衰竭充血性心衰竭充血性心衰竭水腫水腫水腫水腫/充血性心衰竭充血性心衰竭充血性心衰竭充血性心衰竭

ARCOXIA Celecoxib

和其他已知會抑制前列腺素合成的藥物一樣，有些使用ARCOXIA的病患曾出現體液滯留、水腫和高血壓的現象。對先前曾有水腫現象、高血壓、或心臟衰竭的病患，在使用ARCOXIA時，應考慮發生體液滯留、水腫或高血壓的可能性。

有些病人接受NSAIDs(包括Celebrex在內)治療後曾有發生液體滯留與水腫的現象對於液體滯留或心衰竭的病人，應謹慎使用Celebrex

留、水腫或高血壓的可能性。所有NSAIDs，包括etoricoxib，被認為與新發生或再復發的充血性心衰竭有關聯(見副作用)。

MEDAL vs. PRECISIONMEDAL vs. PRECISIONStudy MEDAL PRECISION病人數 34,701patients, 23,504(OA),

9,786(RA) 24,081patients, 21,645(OA),2,436(RA)

平均追蹤 20 months 20 months藥物/劑量 Arcoxia 60-90mg q.d Celecoxib 100 mg b.i.d

Diclofenac 50mg tid or 75mg b.i.d Ibuprofen 600 mg t.i.dNaproxen 375 mg b.i.dNaproxen 375 mg b.i.d

主要結果 APTC : Thrombotic CV events (MI, Stroke, Vascular death)

APTC : Thrombotic CV events (MI, Stroke, Vascular death)

Arcoxia ≒ Diclofenac Celebrex ≒ IbuprofenCelebrex ≒ Naproxen

• 2 Limitations of PRECISION• Adherence and retention were lower

than most CV outcome : 68%discontinue rate

• The dose of celecoxib was moderate (100 mg twice daily)