Table 1 Included studies of tolerability, adverse events, and endoscopically detected ulceration associated with celecoxib in arthritis
| Â | Â | Â | Drug, dose, number randomised | Â | Â | Â | Â | ||
|---|---|---|---|---|---|---|---|---|---|
Study | Details of participants | Relevant medical history | Celecoxib | Placebo | Other | Duration (weeks) | Efficacy outcomes | Safety outcomes | Total in trial (ITT) |
Osteoarthritis | Â | Â | Â | Â | Â | Â | Â | ||
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 | Â | Â | Â | Â | Â | Â | Â | ||
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 | Â | Â | Â | Â | Â | Â | Â | ||
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 |