LEUVEN, Belgium—New findings point to a possible role for intermittent celecoxib (Celebrex®, Pfizer Inc) for  knee or hip osteoarthritis (OA) and support more extensive comparisons of continuous versus intermittent administration. The 6-month pilot study, published in the January issue of the Annals of Rheumatic Diseases,1 showed that intermittent therapy was not significantly less effective than continuous administration. 

"The increased risk of CV events associated with both NSAID and COX-2 selective agents is in part related to high dosage and prolonged use; intermittent therapy might prove to be safer as well as comparably effective." —Arthur Weaver, MD.
"We believe that intermittent treatment could be tried first, failing which, continuous treatment could be initiated," conclude researchers led by Frank P. Luyten, MD, of University Hospitals KULeuven in Leuven, Belgium. "For many patients, intermittent treatment with a rescue drug may be more feasible than continuous treatment."

No significant differences in primary study endpoints

Patients were randomized to receive continuous (n = 62) or intermittent (n = 61)  treatment with celecoxib 200 mg taken once daily for 24 weeks. Patients in the intermittent treatment arm received daily placebo tablets plus a vial of celecoxib 200 mg/day to be used only during OA flares. Patients in both arms could use acetaminophen (to maximum 3 g/day) as a rescue drug.

The primary efficacy endpoint was the area under the curve (AUC) of the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores between baseline and week 24, divided by the time interval. Secondary endpoints included the percentage of days with intake of the flare drug, the AUC of the change in the WOMAC total scores, the mean change from baseline in the WOMAC scores, and the patients' and physicians' global assessments of OA.
 
There were no significant differences between patients in either group in regard to AUC of the change in WOMAC total scores between baseline and week 24 divided by the time interval. In addition, there were no differences in most of the secondary endpoints, the study showed. There was a trend toward fewer days of intake of the flare drug with continuous celecoxib. 

Adverse events were not significantly different between the two arms, but the researchers suspect that intermittent administration might reduce cardiovascular risks that have been of concern with celecoxib and other NSAIDs.

"As continuous treatment with nonselective NSAIDs or COX-2–selective inhibitors could increase the risk for cardiovascular (CV) events in the long term, the potential for harm must be carefully weighed against the benefits," Dr. Luyten writes.

Study adds weight to rheumatologists' suggestions about dosing

"Rheumatologists have suggested this approach in the past because of the poor compliance and frequent switching data with NSAID usage," said Arthur Weaver, MD, a clinical professor of medicine at the University of Nebraska Medical Center, in Omaha. "The increased risk of CV events associated with both NSAID and COX-2 selective agents is in part related to high dosage and prolonged use; intermittent therapy might prove to be safer as well as comparably effective," he told CIAOMed.

"This is the first study to address this issue, but it is a small pilot study and we need a larger double-blind crossover trial of longer duration to address not only efficacy but also safety and cost-effectiveness," Dr. Weaver said.

Reference

1. Luyten FP, Geusens P, Malaise M, et al. A prospective randomized multicentre study comparing continuous and intermittent treatment with celecoxib in patients with osteoarthritis of the knee or hip. Ann Rheum Dis. 2007;66:99–106.