NAMA : Dr. dr.

Rudy Hidayat, SpPD-KR, FINASIM

POSISI : Ketua Divisi Reumatologi
Departemen Ilmu Penyakit Dalam FKUI/
RSUPN Ciptomangunkusumo Jakarta
CURRICULUM VITAE

PENDIDIKAN :
Pendidikan Dokter Umum 1992-1999 FKUB
Pendidikan Spesialis Penyakit Dalam 2004-2008 FKUI
Pendidikan Subspesialis Reumatologi 2009-2012 FKUI
Pendidikan S3/Doktor 2014-2017 FKUI

ORGANISASI :
Ikatan Dokter Indonesia (IDI); Anggota
Perhimpunan Dokter Spesialis Penyakit Dalam Indonesia (PAPDI); Pengurus Besar
Kolegium Ilmu Penyakit Dalam (KIPD); Wasekjen
Perhimpunan Reumatologi Indonesia (IRA); Sekjen Pengurus Besar
Perhimpunan Osteoporosis Indonesia (PEROSI); Pengurus Besar
Perhimpunan SLE Indonesia (PESLI); Anggota
Asia Pacific League of Associations for Rheumatology (APLAR); SIG member
American College of Rheumatology (ACR); International Member
 CURRENT APPROACH IN
DIAGNOSIS AND MANAGEMENT OF
OSTEOARTHRITIS (OA)

Rudy Hidayat

Rheumatology Division, Departement of Internal Medicine

Ciptomangunkusumo Hospital/Faculty of Medicine , Universitas Indonesia
 ILUSTRASI KASUS : Perempuan 58 tahun
keluhan nyeri kedua  Mechanical joint
lutut sejak 6 bulan yl, pain of the knee
terutama saat naik  Age > 50 yo
turun tangga atau  Obesity
jongkok. Tidak ada  Crepitation of the
knee
kaku pagi hari. Tidak
 No sign of
ada kemerahan dan inflammation
bengkak

BB=72 kg; TB=152 cm.

Lutut krepitasi (+),
KNEE
tidak ada efusi OSTEOARTHRITIS ??
maupun deformitas.
VAS=25 mm.
 ACR Classification Criteria
for knee OA
03

01 02

Altman, R, et al. Arthritis Rheum 29:1039, 1986

 MATRIX Glucocorticoid

TGF-
SYNTHESIS IL-1,
IL-1 + PDGF (IL-
IGF-1 1 effect inhibited)
bFGF
promotion inhibition TNF
PDGF -IFN
Retinoids

chondrocyte

IL-1 + -IFN (IL-

1 effect inhibited)
IL-1, Glucocorticoid
TNF- IL-1+ TGF- or
IGF-1 or -IFN
IL-1 + bFGF or PDGF promotion inhibition (IL-1 effect
(IL-1 effect enhanced) inhibited)
MATRIX TGF- (TIMP
increased)
DEGRADATION
Cytokines and other molecules influencing
the synthesis and degradation of matrix by
 Constitutional
Degenerative Obesity
Environment
Genetics Trauma
Multiple factors
(cause – predisposition)

Focal loss of Meniscus

OSTEOARTHRITIS
articular
cartilage Ligament

Marginal and Synovium

central new bone Bursae Synovial fluid
formation
Kuettner KE, et al. Am Acad Orthop Surg 1999 Subcondral bone
 Constitutional
Degenerative Obesity
Environment
Genetics Trauma
Multiple factors
(cause – predisposition)

OSTEOARTHRITIS

Pain Reduced
Problem Quality of Life
Functional
Limitation
 Comprehensive
management
How to Best and latest
manage OA evidence

Individualized
treatment (patient centre care)
 NICE Clinical guideline 2014.
Available at www.nice.org.uk/guidance/CG177
 Comprehensive
management
How to Best and latest
manage OA evidence

Individualized
treatment (patient centre care)
 Recommended therapies for OA
management

Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline
for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol. 2020;72(2):220–33.
Bruyère O, Honvo G, Veronese N, Arden NK, Branco J, Curtis EM, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the
European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2019;49(3):337–50
 2019 ESCEO
2019 ACR/
algorithm
Arthritis VS recommendation
Foundation
for Management
Guideline
of OA
Non-pharmacologic management
Recommendation 2019 ACR 2019 ESCEO
Exercise • Strongly recommended for patients with • Strong recommendation to
knee, hip, and/or hand OA application of a core set
• Form of exercise: aerobic, strengthening, comprising: information
resistance, neuromuscular training, aquatic access/education, weight loss if
• Balance exercise conditionally overweight, and an exercise
recommended for patients with knee program
and/or hip OA • Form of exercise: aerobic,
Weight loss Strongly recommended for patients with knee strengthening, resistance exercise,
and/or hip OA who are overweight or obese hydrotherapy and aquatic exercise
• Apply to subjects aged 70-80 years
Self-efficacy and self- Strongly recommended for patients with knee, Not mention
management hip, and/or hand OA. Effect sizes are generally
programs small, but the benefits are consistent across
studies with minimal risk
Tai chi Tai chi is strongly recommended for patients If OA symptomatic, addition of tai chi
with knee and/or hip OA at any time recommended
Yoga Conditionally recommended for patients with Not mention
knee OA.
Cognitive behavioural Conditionally recommended for patients with Not mention
therapy (CBT) knee, hip, and/or hand OA.
Non-pharmacologic management
Recommendation 2019 ACR 2019 ESCEO
Cane usage Cane use is strongly recommended for patients with knee Not mention
and/or hip OA in whom disease in 1 or more joints is
causing a sufficiently large impact on ambulation, joint
stability, or pain to warrant use of an assistive device.
Knee braces • Tibiofemoral knee braces is strongly recommended for Correction to control
patients with knee OA in whom disease in 1 or both malalignment with knee
knees is causing a sufficiently large impact on braces seems to be
ambulation, joint stability, or pain to warrant use of an preferred to wedged
assistive device, and who are able to tolerate the insoles
associated inconvenience and burden associated with
bracing.
• Patellofemoral braces is conditionally recommended for
patients with patellofemoral knee OA in whom disease
in 1 or both knees is causing a sufficiently large impact
on ambulation, joint stability, or pain to warrant use of
an assistive device.
Kinesiotaping Conditionally recommended for patients with knee and/or If OA symptomatic,
first CMC joint OA. addition of bandage tape
at any time recommended
Non-pharmacologic management
Recommendation 2019 ACR 2019 ESCEO
Hand orthoses or • Strongly recommended for patients If OA symptomatic, addition of walking
walking aids with first CMC joint OA aids (stick, walker, crutches) at any time
• Conditionally recommended for recommended
patients with OA in other joints of the
hand
Acupuncture Conditionally recommended for patients Not mention
with knee, hip, and/or hand OA.
Thermal interventions • Thermal interventions is conditionally If OA symptomatic, addition of thermal
(locally applied heat or recommended for patients with knee, agents (heat and cold) at any time
cold) AND paraffin hip, and/ or hand OA recommended
usage • Paraffin, an additional method of heat
therapy for the hands, is conditionally
recommended for patients with hand
OA.
Radiofrequency Conditionally recommended for patients Not mention
ablation with knee OA.
Modified shoes, lateral Modified shoes as well as lateral and medial If needed to control malalignment, insoles
and medial wedged wedged insoles are conditionally can be used but the correction with knee
insoles recommended against in patients with knee braces seems to be prefered to wedged
and/or hip OA insoles
Non-pharmacologic management
Recommendation 2019 ACR 2019 ESCEO
Massage therapy Conditionally recommended Not mention
against in patients with knee
and/or hip OA.
Acupuncture Conditionally recommended for Not mention
patients with knee, hip, and/or
hand OA.
Manual therapy Conditionally recommended If OA symptomatic, addition of
against over exercise alone in mechanotherapy or manual therapy (flexibility,
patients with knee and/or hip OA. mobilization, stretching) at any time
recommended
Iontophoresis Conditionally recommended Not mention
against in patients with first CMC
joint OA.
Pulsed vibration Conditionally recommended Not mention
against in patients with knee OA
Transcutaneous electrical Strongly recommended against in Not mention
stimulation (TENS) patients with knee and/or hip OA.
Pharmacologic management
Recommendation 2019 ACR 2019 ESCEO
Topical NSAIDs Strongly recommended for Strong recommendation to the use of prescription
patients with knee OA and crystalline glucosamine topical NSAIDs as cyclic add-on
conditionally recommended for analgesia in Step 1, for patients who are still
patients with hand OA. symptomatic after the use of Step 1 background
therapy, and prior to use of oral NSAIDs.
Topical Capsaicin Conditionally recommended for Not mention
patients with knee OA and
conditionally recommended
against in patients with hand OA.
Oral NSAIDs • Strongly recommended for • Strong recommendation to the use of oral NSAIDs
patients with knee, hip, and/or (selective or non-selective) as Step 2 therapy, if
hand OA used only intermittently or for longer cycles; the
• Oral NSAIDs are the initial oral use of oral NSAIDs should be based on the patient
medication of choice in risk profile.
treatment OA regardless • Celecoxib (200 mg/day) may be the preferred oral
anatomic location. NSAID
• Doses should be as low as • All NSAIDs are used at the lowest effective dose for
possible, and treatment should the shortest period of time necessary to control
be continued for as short a pain
time as possible
Pharmacologic management
Recommendation 2019 ACR
Intraarticular • Strongly recommended for patients
glucocorticoid with knee and/or hip OA and
injections conditionally recommended for
patients with hand OA.
• Ultrasound guidance for intraarticular
glucocorticoid injections is strongly
recommended for hip joints (not
required for knee and hand joint)
Acetaminophen • Conditionally recommended for •
patients with knee, hip, and/or hand
OA
• For those with limited pharmacologic
options due to intolerance of or
contraindications to the use of NSAIDs,
acetaminophen may be appropriate for
short-term and episodic use
• Regular monitoring for hepatotoxicity
required for patients receive regular
basis (max dosage of 3 g daily in
divided dose)
2019 ESCEO
Weak recommendation to the use of IA
corticosteroids, which are more effective than
IAHA in the first few weeks of treatment in the
same patient population; more severe pain
may be a better predictor of this short-term
efficacy than inflammatory signs.
Weak recommendation that paracetamol
(acetaminophen) should not be used on a
regular basis as Step 1 long-term
background pharmacological therapy for
the management of knee OA, based on
questionable efficacy and confirmed safety
issues.
• Weak recommendation that paracetamol
(acetaminophen) at doses no greater than
3 g/day may be used as short-term rescue
analgesia only, given on top of a
background of Step 1 chronic therapy with
symptomatic slow-acting drugs for OA
(SYSADOAs)
Pharmacologic management
Recommendation 2019 ACR 2019 ESCEO
Duloxetin • Conditionally recommended for Weak recommendation to the use duloxetine
patients with knee, hip, and/or hand as an alternative to weak opioids in Step 3 of
OA. the algorithm, especially in patients with pain
• While a variety of centrally acting from central sensitization.
agents have been used to management
of chronic pain, only duloxetine has
adequate evidence for use in OA
Opioid • Tramadol conditionally recommended • Weak recommendation to the use of short-
for patients with knee, hip, and/or OA term weak opioids in Step 3 of the
• When patients may have treatment algorithm as the last
contraindications to NSAIDs, find other pharmacological attempt before surgery
therapies ineffective, or have no • The sustained release (SR) formulation of
available surgical options tramadol may be preferred to reduce AEs
• If an opioid is being considered, • Slow upwards titration of tramadol SR
tramadol is conditionally from 50 mg up to 100 mg is recommended
recommended over non-tramadol to improve tolerability and minimize
opioids. treatment discontinuations due to AEs
• Non-tramadol opioid conditionally
recommended against in patients with
knee, hand, and/or hip OA
Colchicine, fish oil, Colchicine, fish oil, and vitamin D Not mention
and vitamin D Conditionally recommended against in
patients with knee, hip, and/or hand OA
Pharmacologic management
Recommendation 2019 ACR 2019 ESCEO
Bisphosphonates Strongly recommended against in patients Not mention
with knee, hip, and/or hand OA.
Glucosamine Strongly recommended against in patients Strong recommendation to the use of
with knee, hip, and/or hand OA prescription crystalline glucosamine sulfate
(pCGS) as Step 1 long-term background therapy
for the management of knee OA, and
discourages the use of other glucosamine
formulations.
Chondroitin Strongly recommended against in patients • Strong recommendation to the use of of
with knee and/or hip OA as are prescription chondroitin sulfate as Step 1
combination products that include long-term background therapy, as an
glucosamine and chondroitin sulfate, but is alternative to pCGS, and the prescription
conditionally recommended for patients drug should be distinguished from low
with hand OA quality over-the-counter products.
• Weak recommendation of combination of
glucosamine and chondroitin sulfate
should not be used in Step 1 of background
therapy, as there is no preparation
containing both prescription products and
no convincing evidence for existing
nonprescription formulations.
Pharmacologic management
Recommendation 2019 ACR 2019 ESCEO
Hydroxychloroquine and Strongly recommended against in patients Not mention
methotrexate with knee, hip, and/or hand OA
Intraarticular hyaluronic Conditionally recommended against in Weak recommendation to the use of
acid injections patients with knee and/or first CMC joint IAHA in patients who have
OA and strongly recommended against in contraindications to NSAIDs, or if the
patients with hip OA. patient is still symptomatic despite the
use of NSAIDs.
Intraarticular botulinum Conditionally recommended against in Not mention
toxin injections patients with knee and/or hip OA
Prolotherapy Conditionally recommended against in Not mention
patients with knee and/or hip OA
Platelet-rich plasma Strongly recommended against in patients Not mention
treatment with knee and/or hip OA.
Stem cell injections Strongly recommended against in patients Not mention
with knee and/or hip OA.
Tumor necrosis factor Strongly recommended against in patients Not mention
inhibitors and with knee, hip, and/or hand OA
interleukin-1 receptor
antagonists
Pharmacologic management
Recommendation 2019 ACR 2019 ESCEO
Other SYSADOAs Not mention Weak recommendation to the use of SYSADOAs other
than CS and pCGS (i.e. ASU and diacerein) as
alternative Step 1 background therapy.
Total knee replacement Not mention Strong recommendation to total knee replacement
surgery for end- stage knee OA patients, which is a
highly selective and cost-effective procedure
although not devoid of adverse outcomes; the role of
other surgical procedures, especially
unicompartemental knee replacement, should be
further investigated.
Transdermal opioid Not mention Weak recommendation to the use of classical oral or
transdermal opioids in end-stage knee OA patients
for whom surgery is contraindicated
 NSAIDs :
focus on etoricoxib
 Mechanism of Action of NSAIDs
Arachidonic acid
Normal condition COX-1 COX-2
Inflammation
(constitutive) X X (inducible)

Non selective
PGH2 NSAIDs PGH2

PGE2 PGI2 TXA2 PGE2 PGI2 TXA2

Stomach Stomach Platelets Synovial membrane,

Kidney Kidney endothelium, vascular smooth
Brain Endothelium muscle, WBCs, brain

• GI protection
• vasodilation • inflammation
• renal perfusion • pain
• fever
• inhibit platelet aggregation

NSAID=nonsteroidal anti-inflammatory drug; COX=cyclooxygenase. Adapted from Wallace JL. Am J Med.IS 1999;107(6A):11S–17S; Hinz B, et al. J Pharmacol Exp Ther. 2002;300(2):367–375; Vanegas H, et32
al.; Prog
Neurobiol. 2001;64(4):327–363; Furst DE. Am J Med. 1999;107(6A):18S–26S; Vane JR, et al. Annu Rev Pharmacol Toxicol. 1998;38:97–120; Fung HB, et al. Clin Ther. 1999;21(7):1131–1157.
 Mechanism of Action of NSAIDs
Arachidonic acid
Normal condition COX-1 COX-2
Inflammation
(constitutive) X X (inducible)

Selective Cox-2
PGH2 NSAIDs PGH2

PGE2 PGI2 TXA2 PGE2 PGI2 TXA2

Stomach Stomach Platelets Synovial membrane,

Kidney Kidney endothelium, vascular smooth
Brain Endothelium muscle, WBCs, brain

• GI protection
• vasodilation • inflammation
• renal perfusion • pain
• fever
• inhibit platelet aggregation

NSAID=nonsteroidal anti-inflammatory drug; COX=cyclooxygenase. Adapted from Wallace JL. Am J Med.IS 1999;107(6A):11S–17S; Hinz B, et al. J Pharmacol Exp Ther. 2002;300(2):367–375; Vanegas H, et al.; Prog
Neurobiol. 2001;64(4):327–363; Furst DE. Am J Med. 1999;107(6A):18S–26S; Vane JR, et al. Annu Rev Pharmacol Toxicol. 1998;38:97–120; Fung HB, et al. Clin Ther. 1999;21(7):1131–1157.
 Classification and
Basic Differences of COXIBs
( Selective COX-2 inhibitors )
Classification Drug Selectivity Chemical
structure

First Celecoxib 30 Sulfonamide

generation Rofecoxib 272 Sulfone

Second Valdecoxib 61 Sulfonamide

generation Etoricoxib 344 Sulfone
Lumiracoxib 433 Phenylacetic acid
derivative
 Less GI side effects
More GI side effects
Diclofenac Celecoxib
Acetosal Indomethacin Ibuprofen
Ketorolac Piroxicam Ketoprofen
Meloxicam COXIB
Rofecoxib
Nimesulide Valdecoxib

preferentially non- preferentially

COX-1 COX-1 COX-2 COX-2
selective
selective selective selective selective
COX
inhibitor inhibitor inhibitor inhibitor
inhibitor

anti-inflammatory
analgesic
 Profil mean or median time to remedication

Etoricoxib has the longest duration of analgesic action

Moore RA, Cochrane 2015; Lierz P Acta Orthopaedica 2012

 Etoricoxib showed 24 minutes Fast Onset of action
& 24 hours Long Last
Pain Relief Score* Over 24 Hours
Etoricoxib 120 mg had a 24-Minute onset of action**
(Dose ranging study)
3.5
3.0
Mean PR score (±SE)*

Etoricoxib 180 mg (n=74)

2.5 Etoricoxib 120 mg (n=76)
Etoricoxib 240 mg (n=76)
2.0 Etoricoxib 60 mg (n=75)
1.5
Ibuprofen 400 mg (n=47)
1.0
Placebo (n=49)
0.5
0.0
0 1 2 3 4 5 6 7 8 12 24
Time (hour) postdose
• Etoricoxib 120 mg had a 24-minute or less onset of action in 50% of patients
• Etoricoxib 120 mg sustained a longer duration of action than ibuprofen
SE = standard error
p<0.001 for etoricoxib 60 and 120 mg and ibuprofen 400 mg vs. placebo over eight hours; p≤0.025 for etoricoxib 120 mg vs. ibuprofen 400 mg
over eight hours
Study included 60, 120, 180, and 240 mg dose for etoricoxib.
*Pain relief (PR) rated on a 0- to 4-point scale (0 = none, 1 = a little, 2 = some, 3 = a lot, 4 = complete); **Median time to onset in 50% of patients
Adapted from Malmstrom K et al. Clin Ther 2004;26:667-79
CLINICAL STUDY
ETORICOXIB
Two multi-centre, 26-week, double-
blind, placebo-controlled, non-
inferiority studies were conducted;
etoricoxib 30 mg qd, celecoxib 200 mg
qd or one of two placebo groups

n in study 1 = 599 patients

n in study 2 = 608 patients

Etoricoxib 30 mg ( very small dose ) qd was at least as

effective as celecoxib 200 mg qd (high dose) in the treatment
of knee and hip OA; both were superior WOMAC
to placebo
Pain Subscale
Bingham, et al. Rheumatology 2007;46:496–507
 Etoricoxib 30 mg demonstrated
comparable efficacy to high-dose ibuprofen (800 mg 3 times daily)
• In a 12-week clinical study of patients with OA
– Patients experienced relief across multiple efficacy end points including WOMAC pain subscale, WOMAC
physical function subscale, and PGADS

Combined primary end points (WOMAC subscales and PGADS) over 12-week period

Ibuprofen Etoricoxib
800 mg 30 mg
Placeboc 3 times dailyc once dailyc
(n=104) (n=210) (n=214)
More
pain
LS mean change

-16.53 to -13.55

-26.53 to -22.97 Less

-27.89 to -23.68
d pain
d

Adapted from Wiesenhutter et al.

OA=osteoarthritis; WOMAC=Western Ontario and McMaster Universities Osteoarthritis Index; PGAD =patient global assessment of disease status.
aTrademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA.
b Etoricoxib 60 mg is the maximum recommended daily dose for the treatment of OA.
cRanges in LS mean changes in the primary end points.
dP<0.001 vs placebo.

1. Wiesenhutter CW et al. Mayo Clin Proc. 2005;80:470–479.

 Efikasi acetaminofen, nsNSAIDs (diklofenak, naproxen), dan COX-2
selective NSAIDs (lumiracoxib, celecoxib) pada OA menunjukkan bahwa
etoricoxib 30 mg menghasilkan perbaikan terbesar (most likely) pada
rasa nyeri dan fungsi fisik.

Stam W.B, et al. The Open Rheumatology Journal 2012;6:6-20

 Etoricoxib dosis 30-90 mg menunjukkan efikasi klinis yang signifikan
pada pasien dengan Osteoartritis selama 52 minggu terapi. Etoricoxib
memiliki efikasi yang setara dengan diclofenac 150 mg dengan efek
samping gastrointestinal yang lebih minimal dibandingkan diclofenac

Curis SP, et al. BMC Musculoskelet Disord 2005 1;6:58

SAFETY ISSUE
of
NSAID
 Etoricoxib was
comparable to
placebo, celecoxib,
and ibuprofen for
effects on the CV
risk markers
measured

12 weeks
• 34,701 patients (24,913 with OA and 9,787 with RA)
• (Included ~ 50% hypertensive pts; ~40% pts with > 2 CV risks)
• Average treatment duration was 18 months (SD 11.8), max 40 months
 MEDAL Program: Confirmed
Upper GI Events
3.0
Etoricoxib 60 and 90 mg pooled (176 events)
Diclofenac 150 mg (246 events) All confirmed
2.5
eventsa
Cumulative Incidence,

Etoricoxib vs diclofenac
HR=0.69 (95% CI: 0.57, 0.83) P=0.0001
2.0
% (95% CI)

1.5

1.0 Complicated
events
P=0.561
0.5
Etoricoxib vs diclofenac
HR=0.91 (95% CI: 0.67, 1.24)
0
0 6 12 18 24 30 36 42
Months
Patients at risk for upper GI events, no.
Etoricoxib 17,412 13,704 10,972 8400 6509 4063 821
Diclofenac 17,289 13,190 10,396 8027 6306 3867 820

GI=gastrointestinal; ITT=intention-to-treat; CI=confidence interval; HR=hazard ratio.

aThese included uncomplicated (perforation, ulcer, and bleeds) and complicated (perforation, obstruction, and bleeds) events.
Adapted from Laine L, et al. Lancet. 2007;369:465–473; Cannon CP, et al. Lancet. 2006;368:1771–1781.
 MEDAL Study: Discontinuations Due
to Clinical or Laboratory GI AEsa

P<0.001b Etoricoxib
20 Diclofenac 150 mg
17.13

15
Rate/100 PY

P<0.001b P<0.001b

10 8.61 8.69 9.13

3.96 4.41
5

0
60 mg/d vs 90 mg/d vs 90 mg/d vs
Diclofenac Diclofenac Diclofenac
Patients With OA Patients With RA

GI=gastrointestinal; AEs=adverse events; mITT=modified intention-to-treat; PY=patient-years; OA=osteoarthritis; RA=rheumatoid arthritis;

COX=cyclooxygenase.
aEvents within 1 year of treatment; bFor both COX proportion hazard and stratified log-rank test.
 MEDAL Program: Cumulative Incidence
of Confirmed Thrombotic CV Events (PP)
7
Etoricoxib 60 and 90 mg pooled (320 events)
6 Diclofenac 150 mg (323 events)
Cumulative Incidence,

5 Etoricoxib vs diclofenac
HR=0.95 (95% CI: 0.81, 1.11)
% (95% CI)

1
P=0.496
0
0 6 12 18 24 30 36 42
Months
Patients at risk
Etoricoxib 16,819 13,359 10,733 8277 6427 4024 805
Diclofenac 16,483 12,800 10,142 7901 6213 3832 815

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

Adapted from Cannon CP, et al. Lancet. 2006;368:1771–1781.
 BIOEQUIVALENCE OF ORINOX

BIOEKUIVALENCE = THERAPEUTIC EQUIVALENCE

ORINOX bioekuivalen dengan originator: EFIKASI,
KEAMANAN, dan KUALITAS setara dengan originator

Aaroon S Kesselheim, JAMA 2008;300(21) 2514-2526

 ORINOX BIOEKUIVALEN VS ORIGINATOR

Mean plasma concentration-time profiles of etoricoxib in human subjects (n = 27) after a

single dose oral administration etoricoxib (Test drug) - ORINOX and the reference (Reference
drug = Originator) : COMPARABLE / SIMILAR  ORINOX BIOEKUIVALEN vs ORIGINATOR

Putri, RSI et al. 2016. Summary Report of Bioequivalence Study. Data on file
 TAKE HOME MESSAGE
• Osteoarthritis is a heterogenous group of common
condition with similar pathologic and radiographic
features
• Diagnosis of OA should be confirmed as a source of
pain and other problems
• Holistic assessment will guide the treatment
• Comprehensive treatment must be part of the OA
management
• Etoricoxib has superior GI safety and proven CV safety
data for chronic use