Published 1/1/2011
Jennie McKee

Longer use of COX-2 inhibitors may improve recovery after TKA

Award-winning study supports multimodal pain management after total knee arthroplasty

COX-2 inhibitors are known to decrease narcotic usage and improve range of motion when administered before total knee arthroplasty (TKA) and throughout hospitalization following surgery, noted William C. Schroer, MD, of the St. Louis Joint Replacement Institute. His study on multimodal pain management received the Lawrence D. Dorr Award at the 2010 annual meeting of the American Association of Hip and Knee Surgeons.

The study by Dr. Schroer and his colleagues, which was funded through an investigator-initiated research grant from Pfizer, was designed to determine whether additional benefits might result from continuing to use a COX-2 selective inhibitor for 6 weeks after surgery. The randomized, double-blind, placebo-controlled study, which used a strict “intent-to-treat” methodology and employed a large study population, determined that the additional administration of the COX-2 selective inhibitor resulted in a less painful and more rapid recovery in TKA patients. According to Dr. Schroer, most TKA patients would be candidates for this protocol.

Evaluating TKA patients
During an approximate 18-month period, 706 patients underwent primary TKA performed by Dr. Schroer. Of those, 178 patients were excluded (
Table 1), and 107 agreed to be enrolled in the study. Dr. Schroer performed all procedures—unilateral primary TKA—using the same implant type and same surgical technique.

“We had a standardized perioperative clinical pathway,” he explained. “All patients were given 400 mgs of celecoxib preoperatively and daily throughout hospitalization.”

Patients were randomized at the time of hospital discharge. The study group received 200 mgs of celecoxib twice daily for 6 weeks, while the control group received a placebo for the same duration. Baseline demographics showed no difference between the two groups.

The researchers collected follow-up data at 3, 6, 12, and 24 weeks and at 1 year postoperatively and compared those scores to preoperative scores.

“Our primary endpoint was narcotic use, based on used pill count,” he said. “Our secondary measures included visual analog scale (VAS) scores at rest, at activity, and at night; knee range-of-motion; Knee Society Scores; Oxford Knee Scores; and SF-12 scores, including physical composite and mental composite scores.”

An independent statistician analyzed the longitudinal data using mixed model repeated measures analysis of variance.

Impact of more COX-2
Dr. Schroer noted that the total narcotic use (measured by pill count) was significantly less in the celecoxib group compared with the placebo group (p = 0.003) (
Fig. 1). While taking nearly twice as much narcotic, the placebo group still had increased pain as measured by the VAS pain scores during activity, at rest, and at night.

Patients in the celecoxib group showed improved Oxford Knee Scores as well as improved Knee Society Scores, including activity and function scores, compared to those in the placebo group. The celecoxib group also had significant improvement in knee flexion (Fig. 2) that remained significantly improved throughout the one year of follow-up.

Although researchers found no difference in the mental composite score between the two groups, patients in the celecoxib group did have improved physical composite scores.

Drawing conclusions
Dr. Schroer said that multimodal pain management strategies incorporating COX-2 inhibitors have been demonstrated to improve knee pain and function throughout hospitalization.

“This study demonstrates that an additional 6 weeks of celecoxib administration can result in a significant improvement in TKA rehabilitation,” he said. “Study patients taking celecoxib required roughly half the narcotics of the control patients.”

Narcotics alone did not control pain as well as narcotics and celecoxib, which, he said, “suggests a benefit of multimodal pain management extending throughout knee rehabilitation.

“Although celecoxib was given for only 6 weeks, pain was significantly improved through 12 weeks of follow-up at rest and at night,” said Dr. Schroer. “Flexion was significantly improved for 12 months.Knee scores were improved just during the first 6 weeks.”

Although only 25 percent of eligible patients volunteered for this study, Dr. Schroer noted that this might be due to the demands of the study as well as patients’ concerns about COX-2 inhibitor safety.

“Celecoxib safety has been studied extensively,” he said. “Rates of cardiovascular events associated with celecoxib are similar to those with placebos and alternative nonsteroidal anti-inflammatory drugs (NSAIDs). The rates of renal dysfunction or hypertension are also similar to those associated with alternative NSAIDs, while the risk for gastrointestinal events is actually lower with celecoxib than with alternative NSAIDs.

“In this study,” he added, “no patient had a celecoxib-related adverse event.”

He noted that future studies may focus on alternative dosing strategies or length of dosing.

“In conclusion,” he said, “patients receiving a COX-2 inhibitor for 6 weeks after primary TKA had more rapid and less painful recovery, which suggests a benefit for continuing a multimodal pain management strategy throughout total knee recovery.”

Coauthors of “Benefits of Prolonged Postoperative COX-2 Inhibitor Administration on Total Knee Arthroplasty Recovery: A Double-Blind, Placebo-Controlled Study” included Paul Diesfeld, PA-C; Angela LeMarr, RN; and Mary Reedy, RN.

Disclosure information: Dr. Schroer—Biomet, Pfizer; the other authors have no conflicts.

Jennie McKee is a staff writer for AAOS Now. She can be reached at mckee@aaos.org

Bottom Line

  • Previous studies have shown that incorporating COX-2 inhibitors into multimodal pain management strategies after TKA reduces knee pain and improves function throughout hospitalization.
  • This randomized, placebo-controlled study shows that continuing to administer COX-2 selective inhibitors for 6 weeks after surgery may enable patients to have less painful and more rapid recoveries and may result in diminished need for narcotics.