In older patients with knee osteoarthritis, treatment with either oral or topical ibuprofen had an equal effect on knee pain after 1 year, according to the results of a randomized controlled trial reported in the December 4 Online First issue of the BMJ.
"If topical ibuprofen is as effective as oral ibuprofen for reducing knee pain but produce fewer adverse effects, then topical treatment might be preferred," write Dr. Martin Underwood, from the Queen Mary University of London, London, United Kingdom, and colleagues. "The popularity of comparatively expensive topical ibuprofen and the importance of adverse effects related to ibuprofen meant that the NHS [National Health Service] Health Technology Assessment programme identified a comparison of oral and topical ibuprofen for osteoarthritis as a priority for research. Here we compare the effect of advice to use oral or topical ibuprofen on knee pain and disability, minor adverse effects related to use of ibupforen, overall pain, and health related quality of life."
At 26 general practices, participants aged 50 years or older with knee pain were enrolled in a randomized trial (n = 282) and a patient preference study (n = 303). The investigators evaluated the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index and major and minor adverse effects associated with advice to use topical or oral ibuprofen.
At 12 months, changes in global WOMAC scores were equivalent with both interventions. The difference between topical and oral ibuprofen was 2 points in the randomized trial (95% confidence interval [CI], –2 to 6) and 1 point in the preference study (95% CI, –4 to 6). There were no differences in major adverse effects between interventions in either the randomized trial or in the preference study.
For secondary outcomes, the only significant differences were observed in the randomized trial. In the group advised to use oral ibuprofen, there were more adverse effects involving the respiratory tract (17% vs 7%; 95% CI for difference, –17% to –2%), the change in serum creatinine levels was 3.7 mmol/L less favorable (0.9 - 6.5 µmol/L), and more participants changed treatments because of adverse effects (16% vs 1%; 95% CI, –16% to –5%).
In the topical group, more participants had chronic pain of grade 2 or 3 at 3 months, and more changed treatment because of lack of effectiveness.
Limitations of the study include lack of generalizability to typical patients presenting in general practice; selection procedure may have produced a study population with a comparatively low risk for adverse effects related to use of ibuprofen; small numbers available for 24-month follow-up; lack of blinding; amount of ibuprofen consumed lower vs many controlled trials; and inability to measure the use of topical or oral ibuprofen purchased over the counter, or to estimate the proportion of prescribed medication the participants actually used.
"Advice to use oral or topical preparations has an equivalent effect on knee pain over one year, and there are more minor side effects with oral ibuprofen," the study authors write. "Topical ibuprofen may be a useful alternative to oral ibuprofen. . . . Participants who wanted a choice predominantly selected topical rather than oral treatment, although those with more severe or widespread pain chose oral rather than topical treatment."
An accompanying article by the same group, but with Dawn Carnes, PhD, from the Queen Mary University of London, London, United Kingdom, as first author, describes a qualitative study of influences on older individuals' decisions concerning choice of topical or oral ibuprofen for knee pain.
"Participants had clear ideas about the appropriate use of oral and topical NSAIDs," these study authors write. "Taking such views into account when prescribing may improve adherence, judgment of efficacy, and the doctor-patient relationship. Tolerance and normalisation of adverse effects in these patients indicate that closer monitoring of older people who use NSAIDs might be needed."
The NHS Health Technology Assessment Programme commissioned both studies. Goldshield Pharmaceuticals supplied the starter packs of topical ibuprofen. Dr. Underwood has received speaker fees from Pfizer, the maker of celecoxib.