Table 1

Included studies of tolerability, adverse events, and endoscopically detected ulceration associated with celecoxib in arthritis

Drug, dose, number randomised


Study

Details of participants

Relevant medical history

Celecoxib

Placebo

Other

Duration (weeks)

Efficacy outcomes

Safety outcomes

Total in trial (ITT)


Osteoarthritis


C-002

OA Hip/Knee (ACR) requiring daily NSAID therapy, FCC 1–3

Stable hypertension, type 2 diabetes

Age 62 (range 40–89) years 61% female ≥ 75% Caucasian

Data not provided

1 × 200 mg/day, n = 36

No placebo

Rofecoxib 1 × 25 mg/day, n = 132

Naproxen 2 × 500 mg/day, n = 128

12

WOMAC

Patient's assessment of arthritis pain

VAS

Patient's global assessment of arthritis

Patient's satisfaction Withdrawal due to lack of efficacy

Withdrawals Adverse events

Serious adverse events

Laboratory tests

396

C-003

OA Knee (ACR) with flare, requiring daily NSAID/analgesic, FCC 1–3, baseline pain 40 on 100 mm VAS.

Age 63 (range 39–90) years Duration of disease 8 (range 0.2–51) years 67% female ≥ 85% Caucasian

Cardioprotective ASA 20% NSAID intolerance 4% GI ulcer 6% GI bleed 1% Renal insufficiency 1%

1 × 200 mg/day, n = 189

n = 96

Rofecoxib 1 × 25 mg/day, n = 190

6

Patient's assessment of arthritis pain WOMAC (total)

Patient's global assessment of arthritis pain

VAS

OASI

Physician's global assessment of arthritis Patient's assessment of satisfaction

Withdrawals Adverse events

Serious adverse events

Laboratory tests

475

C-010

OA Hip/Knee (K-L 2–4), requiring chronic NSAID/analgesic, initial pain 40–90 on 100 mm VAS

Age 63 (range 38–91) years Duration of disease 9 (0.1–54) years 62% female

Cardioprotective ASA 20% GI-related NSAID intolerance 1% Gastroduodenal ulcer 8% GI bleed 0.6% Some type of GI history (unspecified) 48%

1 × 200 mg/day n = 181

n = 172

Paracetamol 4 × 1,000 mg/day, n = 171

6

WOMAC index MDHAQ

Patient's global rating of helpfulness Physician's global assessment of status SF-36 General clinical safety

Withdrawals Adverse events

Serious adverse events

Laboratory tests

524

C-013

OA Knee (ACR) with flare, FCC 1–3 Mean age 62 (range 29–92) years

Duration of disease 10 (0.2–50) years

69% female

90% Caucasian

Cardioprotective ASA permitted NSAID intolerance 13% Gastroduodenal ulcer 16% GI bleed 3% CVD 52%

2 × 40 mg/day, n = 73 2 × 100 mg/day, n = 75 2 × 200 mg/day, n = 73

n = 70

No active comparator

2

Physican's global assessment

Patient's global assessment

Patient's arthritis pain SF-36

Withdrawals Adverse events

Serious adverse events

Laboratory tests

291

C-020

OA knee/hip (ACR) with flare, FCC 1–3 Age 62 (range 21–89) years Duration of disease 9 (0.1–52) years

66% female

79% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 7% Gastroduodenal ulcer 9%

GI bleed 2%

CVD 53%

2 × 50 mg/day, n = 218

2 × 100 mg/day, n = 217

2 × 200 mg/day, n = 222

n = 219

Naproxen 2 × 500 mg/day, n = 216

12

Patient's global assessment

Physician's global assessment

WOMAC Patient's assessment of pain

Withdrawals Adverse events

Serious adverse events

Laboratory tests

1,092

C-021

OA Knee/Hip (ACR) with flare, FCC 1–3 No ulcer at baseline endoscopy Age 61 (range 22–89) years Duration of disease 9 (range 0.1–52)

years

54% female

83% Caucasian

Cardioprotective ASA permitted.

NSAID

intolerance 10% Gastroduodenal ulcer 17%

GI bleed 2%

CVD 60%

2 × 50 mg/day, n = 258

2 × 100 mg/day, n = 239

2 × 200 mg/day, n = 237

n = 247

Naproxen 2 × 500 mg/day, n = 233

12

Patient's global assessment

Patient's assessment of pain Physician's global assessment

WOMAC

Withdrawals Adverse events

Serious adverse events

Laboratory tests Endoscopic ulcers

1,214

C-042

Symptomatic OA Hip/Knee (ACR) ≥ 6 months, requiring NSAID, FCC 1–3

Age 63 (range 34–91) years Duration of disease 7 (0.5–48) years

72% female

94% Caucasian

NSAID

intolerance 2% Gastroduodenal ulcer 3%

GI bleed 0.5%

CVD 45%

2 × 100 mg/day, n = 346

No placebo

Diclofenac 2 × 50 mg/day, n = 341

6

Patient's global assessment

Patient's assessment of pain Physician's global assessment

SF-36

Withdrawals Adverse events

Serious adverse events

Laboratory tests

667

C-047

OA Knee (ACR) with flare, FCC 1–3

Age 63 (29–91) years Duration of disease 9 (0.5–60) years

72% female

84% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 10%

Gastroduodenal ulcer 10%

GI bleed 4%

CVD 62%

2 × 25 mg/day, n = 100

2 × 100 mg/day, n = 101

2 × 400 mg/day, n = 99

n = 101

No active comparator

4

Patient's global assessment

Patient's assessment of pain Physician's global assessment

SF-36 WOMAC

Withdrawals Adverse events

Serious adverse events

Laboratory tests

401

C-054

OA Hip (ACR) with flare, FCC 1–3

Age 62 (28–93) years

Duration of disease 7 (0.1–64) years

66% female

92% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 13% Gastroduodenal ulcer 12%

GI bleed 2%

CVD 60%

2 × 50 mg/day, n = 216

2 × 100 mg/day, n = 207

2 × 200 mg/day, n = 213

n = 217

Naproxen 2 × 500 mg/day, n = 207

12

Patient's global assessment

Patient's assessment of pain Physician's global assessment

SF-36 WOMAC

Withdrawals Adverse events

Serious adverse events

Laboratory tests

1,060

C-060

OA Knee (ACR) with flare, FCC 1–3

Age 63 (29–88) years

Duration of disease 9 (0.1–59) years

66% female

88% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 4%

Gastroduodenal ulcer 6%

GI bleed 2%

CVD 58%

2 × 100 mg/day, n = 231

1 × 200 mg/day, n = 222

n = 231

No active comparator

6

Patient's global assessment

Patient's assessment of pain Physician's global assessment

SF-36

WOMAC

Withdrawals Adverse events

Serious adverse events

Laboratory tests

684

C-087

OA Knee (ACR) with flare, FCC 1–3

Age 61 (18–89) years

Duration of disease 9 (0.1–60) years

70% female

86% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 7%

Gastroduodenal ulcer 16%

GI bleed 2%

CVD 64%

2 × 100 mg/day, n = 241

1 × 200 mg/day, n = 231

n = 243

No active comparator

6

Patient's global assessment

Patient's assessment of pain Physician's global assessmen

WOMAC

Withdrawals Adverse events

Serious adverse events Laboratory tests

715

C-096

OA

Knee/Hip/Hand ≥ 6 months (ACR) requiring daily

analgesic/ NSAID, FCC 1–3 Age 62 (range 21–96) years

76% female Duration of disease 7 (0.3–59) years

Cardioprotective ASA use 7%

CVD 41%

Renal insufficiency 0.2%

Respiratory disease 5%

Diabetes 8%

2 × 100 mg/day, n = 4,393

2 × 200 mg/day, n = 4,407

No placebo

Naproxen 2 × 500 mg/day, n = 905

Diclofenac 2 × 50 mg/day, n = 3,489

12

Patient's global rating of arthritis

Patient's assessment of pain (VAS)

WOMAC

Physician's global assessment of arthritis

Withdrawals Adverse events

Serious adverse events

Laboratory tests

13,194

C-118

OA Knee (ACR) with flare, FCC 1–3

Age 61 (29–88) years

Duration of disease 8 (0.1–62) years

65% female

82% Caucasian

Cardioprotective ASA permitted

NSAID intolerance 3% Gastroduodenal ulcer 8%

GI bleed 1%

CVD 66%

2 × 100 mg/day, n = 199

n = 200

Diclofenac 3 × 50 mg/day, n = 199

6

Patient's global assessment

Patient's assessment of pain Physician's global assessment

WOMAC

Withdrawals Adverse events

Serious adverse events

Laboratory tests

598

C-149

OA

Hip/Knee/Hand (ACR) requiring NSAID, FCC 1–3 Stable treated hypertension Age 74 (range 64–95) years Duration of disease range 0.3–61 years 67% female Majority Caucasian

Cardioprotective ASA 38%

NSAID

intolerance 3%

Gastroduodenal ulcer 10%

GI bleed 3%

Oedema 26%

CHF 5%

1 × 200 mg/day, n = 411

No placebo

Rofecoxib 25 mg/day, n = 399

6

Oedema Aggravated hypertension Renal events

Withdrawals Adverse events

Serious adverse events Laboratory tests

810

C-152

OA Knee (ACR) with flare, FCC 1–3, baseline pain 35 on 100 mm VAS

Age 62 (range 40–88) years Duration of disease 11 (range 0.5–s47) years

71% female

80% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 4%

Gastroduodenal ulcer 9%

GI bleed 0.5%

1 × 200 mg/day, n = 63

n = 60

Rofecoxib 1 × 25 mg/day, n = 59

6

Patient's assessment of arthritis pain

OA VAS

scale

Patient's global assessment of arthritis

WOMAC

Withdrawals Adverse events

Serious adverse events

Laboratory tests

182

C-181

OA

Hip/Knee/Hand (ACR) requiring daily NSAID, FCC 1–3

Stable treated hypertension Age 73 (range 65–96) years Duration of disease 12 (0–63) years

62% female

88% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 2%

Gastroduodenal ulcer 8%

GI bleed 2%

Oedema 27%

CHF 3%

1 × 200 mg/day, n = 549

No placebo

Rofecoxib 1 × 25 mg/day, n = 543

6

Blood pressure Oedema Weight Anti-hypertensive medication

Withdrawals Adverse events

Serious adverse events

Laboratory tests

1,092

C-209

OA Knee with flare (ACR), requiring chronic NSAID, FCC 1–3, initial pain 40–90 on 100 mm VAS

Age 58 (range 45–83) years Duration of disease 5 (range 0.1–36) years

80% female Afro-American population

Data not provided

1 × 200 mg/day, n = 125

n = 66

Naproxen 2 × 500 mg/day, n = 125

6

Patient's assessment of arthritis pain

Patient's global assessment Physician's global assessment

WOMAC

Withdrawals Adverse events

Serious adverse events

Laboratory tests

316

C-210

OA Knee (ACR) with flare, FCC 1–3, requiring daily therapy, baseline pain 40–90 on 100 mm

VAS

Age 65 (range 42–90) years 68% female Duration of disease 5 (0.3–38) years

Asian American population 100% Asian descent

Data not provided

1 × 200 mg/day, n = 145

n = 76

Naproxen 2 × 500 mg/day, n = 141

6

Patient's assessment of arthritis pain

Patient's global assessment

Physician's global assessment

Pain Satisfaction

WOMAC

Withdrawals Adverse events

Serious adverse events

Laboratory tests

362

C-211

OA Knee (ACR) with flare, requiring daily NSAID, FCC 1–3, baseline pain 40–90 on 100 mm VAS

Age 60 (range 40–88) years Duration of disease 6 (range 0.1–36 yrs) years

67% female Hispanic population

Data not provided

1 × 200 mg/day, n = 125

n = 61

Naproxen 2 × 500 mg/day, n = 129

6

Patient's assessment of arthritis pain

Patient's global assessment

Physician's global assessment

WOMAC

Patient's satisfaction

Withdrawals Adverse events

Serious adverse events

Laboratory tests

315

C-216

OA Knee, symptomatic, requiring NSAID, initial pain 40 on 100 mm VAS

Age 63 (range 20–92) years Duration of disease 4 (range 0.1–37) years

66% female Asian population

Cardioprotective ASA 3%

NSAID

intolerance 0.1%

GI bleed 0.2%

Gastroduodenal ulcer 6%

CVD 30%

2 × 100 mg/day, n = 382

n = 192

Loxoprofen 3 × 60 mg/day, n = 385

4

Final global improvement rating

Patient's assessment of arthritis pain Physician's and

patient's global assessment of arthritis

WOMAC

Withdrawals Adverse events

Serious adverse events

Laboratory tests Global safety rating

959

C-249

OA Hip/Knee (K-L confirmed), baseline pain 40–90 on 100 mm

VAS

Age 63 (range 45–89) years Duration of disease 9 (range 0.1–50) years

66% female

≥ 80% Caucasian

Cardioprotective ASA 21% GI-related

NSAID

intolerance 2%

Gastroduodenal ulcer 7%

GI bleed 0.7%

1 × 200 mg/day, n = 189

n = 182

Paracetamol 4 × 1,000 mg/day, n = 185

2 × 6 crossover

WOMAC

MDHAQ

Investigator global assessment

Patient's assessments of helpfulness and arthritis

SF-36

Withdrawals Adverse events

Serious adverse events

Laboratory tests

556


Rheumatoid arthritis


C-012

Adult RA with flare (ACR) ≥ 6 months, requiring NSAID, FCC 1–3 Age 56 (range 21–86) years Duration of disease 11 (range 0.5–50) years

78% female

84% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 9%

Gastroduodenal ulcer 3%

GI bleed 0.6%

CVD 43%

2 × 40 mg/day, n = 80

2 × 200 mg/day, n = 82

2 × 400 mg/day, n = 81

n = 84

No active comparator

4

Patient's global rating of arthritis

Arthritis pain, joint

tenderness, joint swelling

Withdrawals Adverse events

Serious adverse events

Laboratory tests

327

C-022

RA with flare (ACR) requiring NSAID, FCC 1–3 No ulcer at baseline endoscopy Age 54 (range 20–90) years Duration of disease 10 (0.3–58) years

73% female

86% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 10%

Gastroduodenal ulcer 15%

GI bleed 2%

CVD 44%

2 × 100 mg/day, n = 240

2 × 200 mg/day, n = 235

2 × 400 mg/day, n = 217

n = 231

Naproxen 2 × 500 mg/day, n = 225

12

Patient's global assessment of arthritis

Physician's global assessment of arthritic

condition No. of swollen joints

ACR-20

responder index No. of tender/painful joints

Withdrawals Adverse events

Serious adverse events

Laboratory tests Endoscopic ulcers

1,148

C-023

RA (ACR) with flare requiring NSAID, FCC 1–3 Age 55 (range 21–84) years Duration of disease 10 (range 0.3–60) years

73% female

86% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 10%

Gastroduodenal ulcer 8%

GI bleed 1%

CVD 44%

2 × 100 mg/day, n = 228

2 × 200 mg/day, n = 218

2 × 400 mg/day, n = 217

n = 221

Naproxen 2 × 500 mg/day, n = 218

12

Patient's global assessment of arthritis

Physician's global assessment of arthritic

condition No. of swollen joints

ACR -20 responder index No. of tender/painful joints

Withdrawals Adverse events

Serious adverse events

Laboratory tests

1,102

C-041

Adult onset RA (ACR) ≥ 6 months, requiring NSAID, FCC 1–3 No ulcer at baseline endoscopy Age 55 (range 20–85) years Duration of disease10 (0.6–53) years

73% female

98% Caucasian

Cardioprotective ASA not permitted

NSAID

intolerance 7%

Gastroduodenal ulcer 8%

GI bleed 0.7%

CVD 25%

2 × 200 mg/day, n = 326

No placebo

Diclofenac (slow release) 2 × 75 mg/day, n = 329

24

Patient's global assessment

Physician's global assessment

Swollen joints Patient's assessment of arthritis pain

SF-36

Withdrawals Adverse events

Serious adverse events

Laboratory tests

Endoscopic ulcers (not all patients had endoscopy)

655


Osteoarthritis and rheumatoid arthritis


C-062

OA/RA ≥ 3 months, requiring NSAID, FCC 1–3 No ulcer at baseline endoscopy Duration of OA 10 (0.3–50) years, RA 10 (0.4–43) years Age 57 (range 22–86) years

67% female

83% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 13%

Gastroduodenal ulcer 20%

GI bleed 4%

CVD 53%

2 × 200 mg/day, n = 269

No placebo

Naproxen 2 × 500 mg/day, n = 267

12

Patient's global assessment

Physcian's global assessment

SF-36

Withdrawals Adverse events

Serious adverse events

Laboratory tests

Endoscopic ulcers

536

C-071

OA/RA ≥ 3 months, requiring NSAID, FCC 1–3 No ulcer at baseline Age 57 (22–87) years Duration of disease 10 (0.3–48) years

68% female

82% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 7%

Gastroduodenal ulcer 12%

GI bleed 2%

CVD 42%

2 × 200 mg/day, n = 365

No placebo

Diclofenac 2 × 75 mg/day, n = 387

Ibuprofen 3 × 800 mg/day, n = 345

12

Patient's global assessment

Physcian's global assessment

SF-36

Withdrawals Adverse events

Serious adverse events

Laboratory tests

Endoscopic ulcers

1,097

C-102

OA/RA, requiring NSAID >3 months Age 60 (range 18–90) years

69% female

88% Caucasian

Cardioprotective ASA permitted

NSAID

intolerance 9%

Gastroduodenal ulcer 8%

GI bleed 2%

CVD 40%

2 × 400 mg/day, n = 3,987

No placebo

Ibuprofen 3 × 800 mg/day, n = 1,985

Diclofenac 2 × 75 mg/day, n = 1,996

52

Patient's global assessment

Patient's assessment of arthritis pain

SF-36

SODA

Withdrawals Adverse events

Serious adverse events

Laboratory tests

CSUGIEs

7,968

C-105

OA/RA

(documented clinical diagnosis for ≥ 3 months), requiring NSAID, FCC 1–3 Age 50 (range 17–78) years Duration of disease not given 84% female Asian population

Cardioprotective ASA permitted

Gastroduodenal ulcer 0.5%

GI bleed 0.02%

CVD 1%

2 × 100 mg/day, n = 327

No placebo

Diclofenac 2 × 50 mg/day, n = 330

12

Patient's global assessment

Physcian's global assessment

Patient's assessment of arthritis pain

Withdrawals Adverse events

Serious adverse events

Laboratory tests

Endoscopic ulcers

657

C-106

OA/RA

(documented clinical diagnosis), requiring NSAID, FCC 1–3 Age 55 (range 18–80) years Duration of disease not given 17% female ≥ 99% Asian

Cardioprotective ASA permitted Gastroduodenal ulcer 9% GI bleed 3% CVD 10%

2 × 100 mg/day, n = 63

No placebo

Diclofenac 2 × 50 mg/day, n = 61

12

Patient's global assessment Physcian's global assessment Patient's assessment of arthritis pain

Withdrawals Adverse events Serious adverse events Laboratory tests Endoscopic ulcers

124

C-107

OA/RA (documented clinical diagnosis ≥ 3 months) requiring NSAID, FCC 1–3 Age 53 (range 24–88) years Duration OA 4 (0.5–13) years, RA 6 (0.5–19) years 83% female ≥ 99% Asian

Cardioprotective ASA permitted Gastroduodenal ulcer 10% GI bleed 3% CVD 14%

2 × 100 mg/day, n = 44

No placebo

Diclofenac 2 × 50 mg/day, n = 44

12

Patient's global assessment Physcian's global assessment Patient's assessment of arthritis pain

Withdrawals Adverse events Serious adverse events Laboratory tests Endoscopic ulcers

88

C-849 (Pooled 105, 106, 107)

OA/RA

2 × 100 mg/day, n = 434

No placebo

Diclofenac 2 × 50 mg/day, n = 435

12

Endoscopic ulcers (pooled 105, 106, 107)

880


All trials had a quality score of 5/5, and a validity score of 16/16. ACR, American College of Rheumatology; ASA, acetylsalicylic acid; CHF, chronic heart failure; CSUGIE, clinically significant upper gastrointestinal event; CVD, cardiovascular disease; FCC, functional capacity class; GI, gastrointestinal; ITT, intention to treat; K-L, Kellgren-Lawrence; MDHAQ, Multidimensional Health Assessment Questionnaire; NSAID, nonsteroidal anti-inflammatory drug; OA, osteoarthritis; OASI, OA severity index; QS, quality score; RA, rheumatoid arthritis; SODA, sequential occupational dexterity index; VAS, visual analogue scale; VS, validity score; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

Moore et al. Arthritis Research & Therapy 2005 7:R644-R665   doi:10.1186/ar1704

Open Data