Rheumatoid arthritis: rofecoxib led to fewer GI complications than naproxen

Clinical bottom line (level 1b)

  1. Patients with rheumatoid arthritis who received rofecoxib compared with naproxen had fewer GI complications (NNT = 62 at 9 months) , and had similar reductions in symptoms.
Bombardier et al: N Engl J Med 2000; 343 : 1520-1528
Expires January 2004

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 301 centres, in 22 countries

8076 patients (aged mean 58, 80% male) with rheumatoid arthritis

Excluded if
  • on aspirin, ticlopidine, anticoagulatns, cyclosporine, misoprostol, sucralfate, proton-pump inhibitors or H2-receptor antagonists
  • history of cerebrovascular events within previous 2 years
  • history of myocardial infarction or bypass surgery within previous year
  • morbid obesity
  • estimated creatinine clearance < 30 ml/min
  • positive test for faecal occult blood
  • unstable medical condition
  • history of cancer, or alcohol or drug abuse within previous 5 years
  • aged < 50, or < 40 if on long-term steroid therapy
  • history of other type of inflammatory arthritis, upper GI surgery or inflammatory bowel disease

Control Group: (n = 4029, 4029 analysed): naproxen 500 mg twice daily
Experimental Group: (n = 4047, 4047 analysed): rofecoxib 50 mg once daily
Patients took acetaminphen, non-NSAID analgesia, steroids and disease-modifying drugs to control their rheumatoid arthritis
100% followed for 9 months
Outcome notes:
  • clinical upper GI event : gastroduodenal perforation or obstruction, upper GI bleeding, or symptomatic gastroduodenal ulcers

The evidence

Outcome Time to outcome CER EER RRR
(95% CI)		 ARR
(95% CI)		 NNT
(95% CI)
clinical upper GI event 9 months 121
(3.00%)		 56
(1.38%)		 54%
(37% to 66%)		 1.62%
(0.98% to 2.26%)		 62
(44 to 100)

Outcome Control Group
(SD)		 Experimental Group
(SD)		 Mean Difference
(95% CI)
change in Global Disease Activity score -0.53
(0.94) 		-0.51
(0.93) 		0.0
(-0.03 to 0.03)

Comments

  1. Patients were stratified for a history of gastroduodenal ulcer, upper GI bleeding and and gastric perforation
  2. No significant difference in myocardial infarction rates were noted between the two groups (naproxen: 0.1% v. rofecoxib: 0.4%)

Citation

  1. Bombardier C, Laine L, Reicin A, et al: comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000; 343 : 1520-1528
Contributor: Chris Ball, January 2002
Reviewer:

Clinical Question.
Patient rheumatoid arthritis
Intervention or Exposure rofecoxib
Comparison naproxen
Outcome symptom control, gastrointestinal ulcer, perforation, haemorrhage