Table 1 |
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Included studies of tolerability, adverse events, and endoscopically detected ulceration associated with celecoxib in arthritis |
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Drug, dose, number randomised |
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|
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|
Study |
Details of participants |
Relevant medical history |
Celecoxib |
Placebo |
Other |
Duration (weeks) |
Efficacy outcomes |
Safety outcomes |
Total in trial (ITT) |
|
|
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Osteoarthritis |
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|
|
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|
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 |
|
|
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Rheumatoid arthritis |
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|
|
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|
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 |
|
|
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Osteoarthritis and rheumatoid arthritis |
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|
|
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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 |
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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. |
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Moore et al. Arthritis Research & Therapy 2005 7:R644 doi:10.1186/ar1704 |
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