Acute Gouty Arthritis

Slide V.1

 Acute gouty arthritis is characterized by the sudden onset

of excruciating pain.
Gout is a metabolic disease characterized by recurrent
acute attacks of excruciating pain, resulting from
inflammation due to formation, deposition, and release of
monosodium urate crystals in one or more joints of the
extremities.1,2
Epidemiologic studies confirm a worldwide distribution.3
Prevalence in the United States approaches 8.4 cases
per 1000 persons, corresponding to an estimated 2.1
million persons with gout.1
The arthritis of gout is often treated with NSAIDs;
indomethacin is recognized as standard treatment.

Slide V.2

Slide V.3

Management
Gout is managed in the following 3 stages:
1. Treating the acute attack
2. Providing prophylaxis to prevent acute flares
3. Lowering excess stores of urate to prevent
flares of gouty arthritis and to prevent tissue
deposition of urate crystals

Slide V.4

Acute treatment of proven crystal-induced arthritis is

directed at relief of the pain and inflammation. Agents
used in this setting include the following:
1. Nonsteroidal anti-inflammatory drugs (NSAIDs),
such as indomethacin
2. Corticosteroids
3. Colchicine (now less commonly used for acute gout
than it once was)
4. Adrenocorticotropic hormone (ACTH)
5. Combinations of drugs (colchicine plus NSAIDs,
oral corticosteroids plus colchicine, intra-articular
steroids plus colchicine or NSAIDs)
Slide V.5

Non-steroidal anti-inflammatory drugs (NSAIDs) are

a group of drugs that share in common the capacity
to induce:
1. Analgesic effect.
2. Antipyretic effect.
3. Anti-inflammatory effect.

Slide V.6

Classification of NSAIDs:
I. Non-selective COX inhibitors:inhibit the constitutive COX1 and the inducible COX-2 so are liable to be associated
with GIT upset and renal impairment on long term use. This
group is further classified according to chemical structure
into:
1) Salicylates e.g. acetyl salicylic acid.
2) Other NSAIDs:
a) Propionic acid derivatives e.g. Ibuprofen and
naproxen.
b) Oxicams
c) Aryl acetic acid derivatives e.g. Diclofenac.
d) Indole derivatives e.g. Indomethacin and
sulindac.
II. Selective COX-2 inhibitors: selectively inhibit COX2 and
are less liable to be associated with side effects, eg:
etoricoxib, celecoxib, rofecoxib, valdecoxib
Slide V.7

Blinded Clinical Studies in Acute Gouty Arthritis*

Drug
Indomethacin vs. phenylbutazone
Proquazone vs. indomethacin
Sulindac vs. phenylbutazone
Fenoprofen vs. phenylbutazone
Feprazone vs. phenylbutazone
Meclofenamate vs. indomethacin
Flurbiprofen vs. phenylbutazone
Flurbiprofen vs. indomethacin
Indomethacin + allopurinol vs. azapropazone
Tenoxicam
Colchicine vs. placebo
Ketoprofen vs. indomethacin
Etodolac vs. naproxen
Etodolac vs. naproxen
Etoricoxib vs. indomethacin

No. of patients

Year

28
18
47
30
24
20
33
29
93
10
43
59
60
61
150

1973
1978
1979
1979
1980
1983
1985
1986
1987
1987
1987
1988
1990
1991
2001

*List includes only double-blind clinical studies of oral agents based on extensive English-language Med Line literature search
(drug names and gout as search terms; no limit on year of publication; August 2002). All published double-blind clinical studies
may not be included.
Slide V.8

Acute Gouty Arthritis Etoricoxib vs.

Indomethacin Study: Design
Double-blind, randomized, active-comparator
controlled trial

Acute attack of clinically diagnosed gout with moderate,

severe, or extreme pain

Etoricoxib 120 mg once daily or indomethacin 50 mg

three times daily for 7 days

Primary efficacy endpoint

Patient Assessment of Study-Joint Pain*

Key secondary endpoints (evaluated at days 2, 5, and 8)

Investigator assessment of study-joint tenderness
Investigator assessment of study-joint swelling

*Evaluated 4 hours after the initial dose and 4 hours after the morning dose on days 2 to 8.
Adapted from Schumacher HR Jr et al BMJ 2002;324:1488-1492.
Slide V.9

Etoricoxib: Pain Relief Was Similar to That

of Indomethacin in Acute Gouty Arthritis
Patient assessment of pain*
0.0

Etoricoxib 120 mg
(n=72)
Indomethacin 150 mg
(n=71)

LS mean ( SE)

0.5
1.0
1.5
2.0

2.5
3.0
R 4 hr

Day in study

Substantial improvement vs. baseline in patient assessment of

pain at 4 hours**

*04-point Likert scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = extreme)

**LS mean change from baseline 4 hours after initial dose = 0.94; 95% CI, 1.11, 0.76
LS = least squares; R = randomization; SE = standard error; CI = confidence interval
Adapted from Schumacher HR Jr et al BMJ 2002;324:1488-1492; Data on file, MSD.
Slide V.10

Etoricoxib Was Similar to Indomethacin

in Relieving Joint Tenderness and Swelling
of Acute Gouty Arthritis
Tenderness*

Swelling**
0.0

LS mean change from

baseline ( SE)

LS mean change from

baseline ( SE)

0.0
0.5
1.0
1.5
2.0
2.5

0.5
1.0
1.5
2.0
2.5

Day in study
Etoricoxib 120 mg (n=74)

Day in study
Indomethacin 150 mg (n=73)

*03-point Likert scale (0 = no pain; 1 = patient states that there is pain; 2 = patient states that there is pain and winces;
3 = patient states that there is pain, winces, and withdraws)
**03-point Likert scale (0 = none, 1 = palpable, 2 = visible, 3 = bulging beyond joint margins)
LS = least squares; SE = standard error; R = randomization (baseline) visit
Adapted from Boice JA et al. Poster presented at the 3rd Annual European Congress of Rheumatology, 2002;
Data on file, MSD.
Slide V.11

Etoricoxib: Early Pain Relief Was Similar to

Indomethacin in Acute Gouty Arthritis
Patients with mild or no pain
100
90

89
83
78

Percent of patients

80

60

60

55

40
32
23
20

0
R

4 hr

Day in study
Etoricoxib 120 mg (n=74)

Indomethacin 150 mg (n=75)

Adapted from Schumacher HR Jr et al BMJ 2002;321:1488-1492; Data on file, MSD.

Slide V.12

Etoricoxib Was Better Tolerated Than

Indomethacin in Acute Gouty Arthritis
Clinical Trial
Etoricoxib
(n=75)
%

Indomethacin
(n=75)
%

22.7

46.7

With serious drug-related AEs

0.0

1.3

Discontinued due to drug-related AEs

2.7

9.3

Discontinued due to serious

drug-related AEs

0.0

1.3

% of Patients
With drug-related AEs*,**

AE = adverse events
*Prespecified for statistical testing
**p=0.003
Adapted from Schumacher HR Jr et al BMJ 2002;321:1488-1492; Data on file.
Slide V.13

Etoricoxib Was Better Tolerated vs. Indomethacin

for Drug-Related Adverse Events in Acute Gouty
Arthritis Clinical Trial

Adverse Experiences*
Patients with one or more AE

Etoricoxib
(n=75)
%

Indomethacin
(n=75)
%

22.7

46.7

Body site as a whole/site unspecified

Dizziness

9.3
5.3

24.0
20.0

Cardiovascular
Hypertension

8.0
8.0

13.3
10.7

Digestive system
Nausea

8.0
0.0

22.7
6.7

Nervous system
Headache
Somnolence

2.7
1.3
1.3

12.0
6.7
5.3

*% of patients with specific drug-related clinical AEs by body system

Adapted from Boice JA et al. Poster presented at the 3rd Annual European Congress of Rheumatology, 2002.
Slide V.14

Etoricoxib Was Similar to Indomethacin

in Acute Gouty Arthritis
In a study of acute gouty arthritis,

Etoricoxib provided rapid and powerful relief

of the excruciating pain of acute gout

Etoricoxib 120 mg once daily was similar to

the gold standard indomethacin 150 mg
(50 mg three times daily)

Etoricoxib 120 mg was generally well tolerated

Adapted from Schumacher HR Jr et al BMJ 2002;321:1488-1492; Boice JA et al. Poster presented at the 3rd Annual
European Congress of Rheumatology, 2002.
Slide V.15