Topical NSAIDs for strains and sprains

Clinical bottom line

Topical NSAID was significantly better than placebo in 19 of the 26 trials, with a pooled relative benefit of 1.6 (1.4 to 1.7), and NNT of 3.8 (3.4 to 4.4) compared with placebo for the outcome of half pain relief at seven days. Ketoprofen was significantly better than all other topical NSAIDs.

Local adverse events, systemic adverse events, or withdrawals due to an adverse event were rare, and no different between topical NSAID and placebo.

Background

The utility of topical NSAIDs has been questioned. This systematic review updated a previous review by accepting only higher quality trials (randomised, double blind), omitting salicylates, and adding newer trials.

Reference

L Mason et al. Topical NSAIDs for acute pain: a meta-analysis. BMC Family Practice 2004 5:10 (http://www.biomedcentral.com/1471-2296/5/10)

Systematic review

The review sought studies in four electronic databases, reviews, and by writing to all companies worldwide marketing topical NSAIDs.

Date review completed: April 2003
Number of trials included: 24 placebo controlled, eight active controlled, four with both active and placebo controls.
Number of patients: 2,853 patients in placebo controlled trials, 433 in active controlled trials had analysable data.
Control groups: Placebo gel or cream, or oral NSAID.
Main outcomes: Clinical success, representing approximately a 50% reduction in pain over seven days.

Results

Placebo controlled trials

Twenty-six trials with information from 2,853 patients were analysed for efficacy. In 19 of the 26 trials topical NSAID was significantly better than placebo. Topical NSAIDs as a class were significantly better than placebo (Table 1), with an NNT of 3.8 (3.4 to 4.4). There were 22/26 studies with higher quality and validity scores that minimised bias, and these also had an NNT of 3.8 (Table 1).

Table 1: Main results for topical NSAIDs in strains and sprains

	Number of		Success with
Trials	Trials	Patients	Treatment	Placebo	Relative benefit (95% CI)	NNT (95% CI)
All trials	26	2853	993/1531	512/1322	1.6 (1.4 to 1.7)	3.8 (3.4 to 4.4)
Quality score Ž3 and validity score Ž9	22	2511	876/1355	440/1156	1.6 (1.4 to 1.8)	3.8 (3.3 to 4.4)
Efficacy by topical NSAID
ketoprofen	6	517	203/261	101/256	2.1 (1.7 to 2.5)	2.6 (2.2 to 3.3)
ibuprofen	5	365	112/183	67/182	2.0 (1.5 to 2.6)	4.1 (2.9 to 6.9)
felbinac	3	413	112/210	57/203	1.6 (1.2 to 2.2)	4.0 (2.9 to 6.2)
piroxicam	3	563	179/283	118/280	1.4 (1.1 to 1.7)	4.7 (3.4 to 7.7)
indomethacin	3	394	95/197	76/197	1.3 (0.99 to 1.6)	10 (5.2 to infinity)
Adverse events						NNH 95% CI
Local adverse events	23	2741	65/1464	60/1277	1.6 (1.0 to 2.5)	Not calculated
Systemic adverse events	23	2685	40/1437	30/1248	1.4 (0.9 to 2.0)	Not calculated
Adverse events withdrawals	24	3011	13/1601	10/1410	1.6 (0.8 to 3.4)	Not calculated

Efficacy estimates were also made for five individual drugs studied in at least three trials (Table 1). All were significantly better than placebo, but in the case of indomethacin just so. Ketoprofen had the lowest (best) NNT of 2.6 (2.2 to 3.3). The result for ketoprofen was significantly better than for ibuprofen, felbinac, piroxicam and indomethacin (Figure 1).

Figure 1: NNTs for individual topical NSAIDs

Trials with oral NSAIDs

Three trials, with 433 patients, compared a topical NSAID with an oral NSAID (indomethacin 75 mg daily in one trial and ibuprofen 1,200 mg daily in two). Overall rates of treatment success were similar for topical NSAID (57%) and oral NSAID (62%), with no statistically significant difference (relative benefit 0.9; 0.8 to 1.1).

Adverse events

There was no statistically significant difference between the numbers of patients experiencing one or more local adverse events (4%), one or more systemic adverse events (2.5%), or the numbers of patients withdrawing due to an adverse event (0.8%), with topical NSAIDs than with placebo (Table 1). Systemic adverse events and adverse event withdrawals did not differ between topical and oral NSAID.

Comment

This systematic review confirms the results of a previous review. Topical NSAIDs are effective for pain relief in conditions like strains and sprains, using the outcome of at least half pain relief over seven days. These conditions are usually self-limiting, and with time get better by themselves, so over periods longer than a week less difference would be expected.

In limited studies topical NSAIDs were no different from standard doses of oral NSAID. Topical NSAIDs were not associated with any higher rate of adverse events, either local or systemic.

Of all the topical NSAIDs available, ketoprofen has the best (lowest) NNT, and was significantly better than others.