RE: Frakes EP, Risser RC, Ball TD et al. Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin 2011;27:2361-72
Dear Editor,
In 2011, we published a manuscript disclosing the primary results of a 10 week clinical trial of flexible-dose treatment with duloxetine 60/120 mg/day in adult outpatients, who had persistent pain of at least moderate severity due to osteoarthritis of the knee, despite having received optimized oral nonsteroidal anti-inflammatory drugs. As the patients were not re-randomized prior to dose escalation, the results of a post hoc efficacy comparison between the duloxetine groups or to placebo would be biased. Therefore, we wish to describe the post hoc efficacy results for the duloxetine escalation group that might be of interest to clinicians.
Three weeks after randomization, 153 of the 264 patients randomized to duloxetine treatment were escalated to 120 mg/day, because they still reported weekly average pain severity of at least 4 on a 0–10 scale. The diary-based baseline pain severity in the escalated group was a mean of 6.8 and a standard deviation (SD) of 1.3. The estimated mean change from baseline in pain severity at Week 8 was −2.0 (1.8), and the endpoint pain severity rating was 4.8 (1.9). In addition, 66 (43.1%) of the 153 escalated patients met response criteria at endpoint that was defined as at least a 30% reduction from baseline in pain severity. Of note, 24 (15.7%) of the escalated patients had actually met the relative difference response criteria at Week 3, but were nonetheless escalated since they still met the absolute escalation criteria.
Our flexible dose design for this study may reflect clinical practice, where a dose is increased when a patient has not achieved satisfactory pain relief, but the lack of re-randomization at 3 weeks to the escalated dose or to maintaining dose weakens our ability to make valid statistical comparisons involving the dose-escalated group.