The Journal of Informed Pharmacotherapy 2000;203-205.
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Reviewer: Carlo Marra, Pharm.D.
Reviewer's email address: firstname.lastname@example.org
Reviewer's profession/specialty: Pharmacy/Research/Rheumatology; funded by CIHR/Arthritis Society Fellowship Award
Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A et al. Gastrointestinal toxicity with celecoxib vs. nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000;284:1247-55. PubMed Cit
The primary objective of this trial was to compare the annualized incidence of upper GI ulcer complications (gastric or duodenal perforation, gastric outlet obstruction or upper GI bleeding) in osteoarthritis (OA) or rheumatoid arthritis (RA) adult patients treated with celecoxib (at dosages 2-4-fold higher than recommended by the FDA) or an NSAID (diclofenac or ibuprofen).
1. Was assignment of patients randomized?
Yes. Patients were randomly assigned to receive celecoxib 400mg twice daily; ibuprofen 800 mg 3 times daily; or diclofenac 75 mg twice daily.
Yes. Baseline characteristics between the celecoxib and NSAID groups (combined) did not differ significantly. All measured potential confounding variables were equally balanced across groups.
Yes. All patients were treated equally from both diagnostic and therapeutic perspectives. Outcomes were adjudicated by a blinded GI events committee not involved in the care of the patient.
1. How large was the treatment effect?
The annualized incidence of upper GI ulcer complications was 0.76% in the celecoxib group as compared to 1.45% in the NSAID groups (p=0.09). This translates into an ARR of 0.69% and a NNT of 145 patients (CI 60 to -1098) treated for one year to avoid one upper GI ulcer complication.
Secondary analyses revealed that the annualized incidence of upper GI ulcer complications plus symptomatic ulcers was 2.08% in the celecoxib arm as compared to 3.54% in the NSAID arms (ARR 1.46%, NNT 69 patients treated for one year to avoid one event, p=0.02). In patients on concurrent low dose ASA, the potential reduction in GI toxicity of celecoxib as compared to the NSAID was not evident. However, in non-ASA users, the annualized incidence of upper GI ulcer complications was significantly lower with celecoxib as compared to the NSAID groups (ARR 0.83%, NNT to avoid one upper GI ulcer complication for one year was 121, p=0.04).
2. How precise was the estimate of the treatment effect?For the primary outcome (upper GI ulcer complications) the 95% CI for the RR crossed one indicating the possibility of a null result and thus, an imprecise estimate of the effect. The 95% CI for the RR for the secondary outcome variables were fairly wide, but none crossed one.
2. Were all clinically important outcomes considered?
It would appear that the incidence of upper GI ulcer complications plus symptomatic ulcer is lower in patients treated with celecoxib than those on regular non-specific COX inhibitors. In addition, it would appear that the annualized incidence of upper GI complications is reduced through the use of celecoxib in patients not receiving low dose ASA. However, both of these outcomes were secondary in the CLASS trial. The primary outcome, the annualized incidence of upper GI complications in all study entrants, was not significantly different between the study arms although there was a trend for a modest reduction in events in the celecoxib arm. Since the use of concomitant anti-ulcer drugs was prohibited, it is unclear how the differences would manifest in real world use of these agents. In addition, the cost-effectiveness of celecoxib as compared to traditional non-specific COX inhibitors has not been established. Considering the widespread use of these agents, further research is warranted to determine both their economic impact and the outcomes achieved when used outside of a clinical trial.
1. Marra CA, Esdaile JM, Sun H, Anis AH. The cost of COX inhibitors: How selective should we be? J Rheumatol 2000 (in press)).
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