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Table 1 Included studies of tolerability, adverse events, and endoscopically detected ulceration associated with celecoxib in arthritis

From: Tolerability and adverse events in clinical trials of celecoxib in osteoarthritis and rheumatoid arthritis: systematic review and meta-analysis of information from company clinical trial reports

    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
  1. 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.