- Design
- Open-label randomised controlled trial, 1:1, single tertiary academic hospital, 14 days
- Population
- 89 patients completing follow-up with chronic symptomatic knee osteoarthritis (45 celecoxib, 44 combination)
- Primary outcome
- Pain on visual analogue scale and function on WOMAC at days 3, 7 and 14
- Effect
- Visual analogue reduction day 3 3.4 vs 2.0 (P < 0.01) and day 7 3.9 vs 3.3 (P = 0.02), no difference at day 14; WOMAC better with combination at all three time points (all P < 0.01)
Ninety patients with symptomatic knee osteoarthritis at a tertiary hospital were randomised 1:1, open-label, to oral celecoxib 200 mg once daily or the same plus a topical flurbiprofen patch twice daily, and assessed at days 3, 7 and 14. Eighty-nine completed.
The combination worked faster. Visual analogue pain reduction was larger at day 3 (3.4 against 2.0, P < 0.01) and still larger at day 7 (3.9 against 3.3, P = 0.02), but by day 14 the two groups had converged and the difference was gone. WOMAC improvement was greater with the combination at all three time points (all P < 0.01), and at day 14 the combination group also had better SF-36 health domain scores and patient global assessment.
The pattern is worth reading precisely, because it is easy to summarise wrongly. This is not evidence that combining oral and topical NSAIDs gives better pain control in knee osteoarthritis; it is evidence that it gives faster pain control, with the pain advantage spent by two weeks. That still has a use - the patient who cannot mobilise, the one waiting for physiotherapy to start, the flare that needs to settle before anything else can happen - and speed is a legitimate goal in its own right when immobility is the thing doing the damage.
It is also a short, open-label trial in 89 patients with no placebo patch, which matters more than usual because a visible patch applied twice daily is a strong expectation cue and pain is the outcome. Combining oral and topical NSAIDs also adds systemic exposure, which the gastrointestinal and renal risk calculation has to absorb.
- Consider adding a topical NSAID to an oral one for rapid symptom control, for days rather than weeks
- Stop the patch once the flare settles; the pain advantage had gone by day 14
- Count the topical NSAID in the total systemic exposure when assessing gastrointestinal and renal risk
- Avoid in anyone where the oral NSAID itself is already borderline - this adds, it does not substitute
- Open-label with no placebo patch, so some of the day 3 difference is expectation
Why it matters
It reframes combined oral and topical NSAIDs as a short-term flare strategy rather than a better maintenance regimen.
Don't overread it
Open-label with no placebo patch - the earliest and largest differences are the ones expectation would most affect.
The statistics, in plain English
The day 3 difference - 3.4 against 2.0 points on a visual analogue scale - is large and comfortably beyond what patients can detect. The day 7 difference of 3.9 against 3.3 is statistically significant at P = 0.02 but around half a point, which is at or below the threshold most patients would notice. And by day 14 there is nothing. That trajectory is the finding: an effect on speed, not on destination. The absence of a placebo patch in an open-label trial matters most at the early time points, where expectation effects on a self-reported pain score are strongest - which is precisely where the difference was largest.
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