Salicylate‐containing rubefacients for acute and chronic musculoskeletal pain in adults

Sheena Derry; Paul R L Matthews; Philip J Wiffen; R Andrew Moore

doi:10.1002/14651858.CD007403.pub3

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Figure 1

Study flow diagram.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 4

Forest plot of comparison: 1 Rubefacient versus placebo, outcome: 1.1 Clinical success (eg 50% reduction in pain).

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Figure 5

Forest plot of comparison: 1 Rubefacient versus placebo, outcome: 1.4 Adverse events.

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Analysis 1.1

Comparison 1 Rubefacient versus placebo, Outcome 1 Clinical success (eg 50% reduction in pain).

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Analysis 1.2

Comparison 1 Rubefacient versus placebo, Outcome 2 Adverse events.

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Analysis 1.3

Comparison 1 Rubefacient versus placebo, Outcome 3 Withdrawals.

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Analysis 2.1

Comparison 2 Rubefacient versus active control, Outcome 1 Clinical success (eg 50% reduction in pain).

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Analysis 2.2

Comparison 2 Rubefacient versus active control, Outcome 2 Adverse events.

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Analysis 2.3

Comparison 2 Rubefacient versus active control, Outcome 3 Withdrawals.

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Salicylate‐containing topical rubefacients compared with topical placebo for acute and chronic painful conditions
Patient or population: adults with strains or sprains (acute) or osteoarthritis or low back pain (chronic) Settings: community Intervention: salicylate‐containing topical rubefacient Comparison: topical placebo
Outcomes	Probable outcome with intervention	Probable outcome with comparator	RR NNT, NNTp, or NNH (95% CI)	No of studies, participants	Quality of the evidence (GRADE)	Comments
Clinical success (eg 50% reduction in pain) Acute conditions	640 in 1000	335 in 1000	RR 1.9 (1.5 to 2.5) NNT 3.2 (2.4 to 4.9)	4 studies 324 participants	⊕⊝⊝⊝ very low	Most recent, largest study showed no effect Note NNT cannot be trusted because of low numbers and poor quality studies
Clinical success (eg 50% reduction in pain) Chronic conditions	447 in 1000	284 in 1000	RR 1.6 (1.2 to 2.0) NNT 6.2 (4.0 to 13)	6 studies 455 participants	⊕⊝⊝⊝ very low	Most recent, largest studies showed no effect Note NNT cannot be trusted because of low numbers and poor quality studies
Adverse events ‐ any adverse events Acute and chronic conditions combined	152 in 1000	94 in 1000	RR 1.6 (1.2 to 2.0) NNH 17 (9.9 to 58)	11 studies 984 participants	⊕⊕⊝⊝ low	Inadequate reporting of adverse events is common Acute and chronic conditions combined
Adverse events ‐ local adverse events Acute and chronic conditions combined	56 in 1000	24 in 1000	RR 2.2 (1.1 to 4.1) NNH 31 (16 to 300)	10 studies 869 participants	⊕⊝⊝⊝ very low	Small numbers of events Acute and chronic conditions combined
Withdrawals ‐ lack of efficacy Acute and chronic conditions combined	24 in 1000	72 in 1000	RR 0.4 (0.2 to 0.9) NNTp 21 (12 to 120)	5 studies 501 participants	⊕⊝⊝⊝ very low	Small numbers of events Acute and chronic conditions combined
Withdrawals ‐ adverse events Acute and chronic conditions combined	49 in 1000	11 in 1000	RR 4.2 (1.5 to 12) NNH 26 (15 to 85)	7 studies 737 participants	⊕⊝⊝⊝ very low	Small numbers of events Acute and chronic conditions combined
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
CI: confidence interval; RR: risk ratio; NNT: number needed to treat; NNTp: number needed to prevent an event happening; NNH: number needed to harm

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Comparison 1. Rubefacient versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical success (eg 50% reduction in pain) Show forest plot	10		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Acute conditions	4	324	Risk Ratio (M‐H, Fixed, 95% CI)	1.93 [1.51, 2.46]
1.2 Chronic conditions	6	455	Risk Ratio (M‐H, Fixed, 95% CI)	1.58 [1.22, 2.04]
2 Adverse events Show forest plot	11		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Any adverse event	11	984	Risk Ratio (M‐H, Fixed, 95% CI)	1.56 [1.19, 2.04]
2.2 Local adverse events	10	869	Risk Ratio (M‐H, Fixed, 95% CI)	2.15 [1.12, 4.12]
3 Withdrawals Show forest plot	7		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Lack of efficacy	5	501	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.15, 0.87]
3.2 Adverse events	7	737	Risk Ratio (M‐H, Fixed, 95% CI)	4.19 [1.52, 11.56]

Comparison 1. Rubefacient versus placebo

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Comparison 2. Rubefacient versus active control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical success (eg 50% reduction in pain) Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Acute	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Chronic	2		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Adverse events Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.1 Any adverse events	3		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Local adverse events	3		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Withdrawals Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.1 Lack of efficacy	2		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Adverse events	3		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 2. Rubefacient versus active control

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