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Non-steroidal anti-inflammatory drugs (NSAIDs) for treating lateral elbow pain in adults

  1. Porjai Pattanittum1,
  2. Tari Turner2,
  3. Sally Green2,
  4. Rachelle Buchbinder3,*

Editorial Group: Cochrane Musculoskeletal Group

Published Online: 31 MAY 2013

Assessed as up-to-date: 11 OCT 2012

DOI: 10.1002/14651858.CD003686.pub2

How to Cite

Pattanittum P, Turner T, Green S, Buchbinder R. Non-steroidal anti-inflammatory drugs (NSAIDs) for treating lateral elbow pain in adults. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD003686. DOI: 10.1002/14651858.CD003686.pub2.

Author Information

  1. 1

    Faculty of Public Health, Khon Kaen University, Department of Biostatistics and Demography, Khon Kaen, Khon Kaen, Thailand

  2. 2

    Monash University, School of Public Health & Preventive Medicine, Melbourne, Victoria, Australia

  3. 3

    Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Monash Department of Clinical Epidemiology at Cabrini Hospital, Malvern, Victoria, Australia

*Rachelle Buchbinder, Monash Department of Clinical Epidemiology at Cabrini Hospital, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Suite 41, Cabrini Medical Centre, 183 Wattletree Road, Malvern, Victoria, 3144, Australia. rachelle.buchbinder@monash.edu.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 31 MAY 2013

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Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

 
Summary of findings for the main comparison. Topical NSAIDs compared to placebo for treating lateral elbow pain in adults

Topical NSAIDs compared with placebo for treating lateral elbow pain in adults

Patient or population: Adults with lateral elbow pain
Settings: Outpatient settings in high-income countries
Intervention: Topical NSAIDs
Comparison: Placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

PlaceboTopical NSAIDs

Pain

0 to 10 visual analogue scale (0 = no pain)
The median pain in the placebo groups was
3.78 points1
The mean pain in the intervention groups was
1.64 lower
(2.42 to 0.86 lower)
153
(3 studies)
⊕⊝⊝⊝
very low2,3,4
Absolute reduction in pain 16% (8% to 24%); relative percent reduction 32% (17% to 47%).

NNTB 7 (3 to 21).

Treatment success

Fair, good or excellent effectiveness
488 per 10005727 per 1000 (507 to 1000)6RR 1.49 (1.04 to 2.14)85

(1 study)
⊕⊕⊝⊝
low2,7
Absolute risk difference 24% more success with NSAIDs (4% to 44%); relative change 49% improvement (4% to 114%).

NNTB 4 (2 to 25).

Function/disabilitySee commentSee commentNot estimable-See commentNo studies reported this outcome.

Quality of lifeSee commentSee commentNot estimable-See commentNo studies reported this outcome.

Withdrawal due to adverse eventsSee commentSee commentNot estimable185

(4 studies)
⊕⊕⊝⊝
low2,3,4
No participants withdrew because of adverse effects with topical NSAIDs or placebo. Some studies reported infrequent and mild adverse effects such as rash.

Adverse events12 per 100020 per 1000 (3 to 158)RR 1.55 (0.20, 12.14)153 (3 studies)⊕⊕⊝⊝
low2,3,4
Absolute risk difference 0% (5% fewer to 6% more); relative change 55% more events with NSAIDs (80% fewer to 114% more).

NNTH not applicable.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval.

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.

 1 Median of reported mean pain in placebo group for three studies included in the meta-analysis.
2 Included studies were of low quality and small sample size.
3 Only one study used adequate concealment of allocation.
4 One crossover study did not present within-participant data; one RCT did not report baseline data by group and one RCT reported an imbalance of baseline data in terms of pain between treatment and control groups.
5 Risk of treatment success in the placebo group of the single study reporting this outcome.
6 Upper limit of the CI was rounded down to 1000 as the highest possible value for an absolute effect.
7 Imbalance of baseline data between treatment and control groups.

 Summary of findings 2 Oral NSAIDs compared to placebo for treating lateral elbow pain in adults

 Summary of findings 3 Oral NSAIDs compared to glucocorticoid injection for treating lateral elbow pain in adults

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

This Cochrane review is one of a series of Cochrane reviews of interventions for lateral elbow pain in adults and is an update of a Cochrane review first published in 2002 (Green 2002).

 

Description of the condition

Lateral elbow pain is described by many analogous terms in the literature, including tennis elbow, lateral epicondylitis, lateral epicondylalgia, rowing elbow, tendonitis of the common extensor origin, and peritendonitis of the elbow. For the purposes of this review, the term lateral elbow pain will be used as it best describes the site of the pain, and will allow for greater clarity of inclusion.

Lateral elbow pain is a common disorder with a prevalence of 1% to 3% in adults of working age (Allander 1974; Roquelaure 2006; Shiri 2006; Walker-Bone 2004). It affects up to 15% of workers in at-risk industries and is a common sports injury ( Hume 2006; Ranney 1995; Walker-Bone 2004). It has a reported incidence of between 4.8% and 5.3% in Dutch general practice, with an incidence of 11 per 1000 person-years in the 40 to 60-year age group-the age group most affected (Bot 2005). Shiri 2006 reported no gender difference in the prevalence of lateral elbow pain, although a slight excess of men (Walker-Bone 2004) or women (Roquelaure 2006) has been reported.

The acute pain of lateral elbow pain usually lasts 6 to 12 weeks and often results in work absence (Mallen 2009). For most it is a self-limiting condition, but for some episodes may persist for up to 2 years. One study found that 80% of participants with elbow pain already greater than 4 weeks' duration recovered after one year without any specific treatment (Bisset 2005). Prognostic factors at least moderately associated with a poorer outcome at one year include previous occurrence, high physical strain at work, manual jobs, high baseline levels of pain and/or distress, and inadequate social support. Depression and ineffective coping skills have also been found to strongly predict disability from lateral elbow pain (Alizadehkhaiyat 2007). A recent ultrasound study determined that a lateral collateral ligament tear or large (≥ 6 mm) intrasubstance tears were associated with a poorer outcome, but no relationship between tendon thickness or neovascularity and outcome was seen (Clarke 2010). Fewer than 10% of patients with lateral elbow pain need to undergo surgery (Nirschl 1979).

 

Description of the intervention

Non-steroidal anti-inflammatory drugs (NSAIDs) have long been the first line of treatment, along with simple analgesics, for all sites of tendonitis, including that of the lateral elbow. Several types of oral and topical NSAIDs are available over-the-counter or on prescription. These drugs are among the most frequently prescribed in the developed world. They are also well known to be associated with significant morbidity, particularly in terms of gastrointestinal and cardiovascular adverse effects (Biskupiak 2006; Garcia 2001; Kearney 2006).

 

How the intervention might work

NSAIDs work by preventing an enzyme called cyclooxygenase (COX) from making prostaglandins. Prostaglandins are hormone-like chemicals in the body that contribute to inflammation, pain and fever. By reducing production of prostaglandins, NSAIDs help relieve symptoms related to fever, inflammation and mild to moderate pain.

Two COX enzymes-COX-1 and COX-2-produce prostaglandins. However, only COX-1 produces prostaglandins that support platelets and protect the stomach lining. It also helps to maintain kidney function. COX-2 is produced when joints are injured or inflamed.

Most NSAIDs are nonselective inhibitors. This means that they inhibit both COX-1 and COX-2. Because nonselective NSAIDs also act on COX-1, they may decrease protective stomach prostaglandin levels, leading to stomach ulcers. A newer class of NSAIDs-the coxibs-selectively inhibit COX-2 and therefore have less adverse effect on the stomach.

 

Why it is important to do this review

NSAIDs are often used to treat lateral elbow pain. In our previous review, we concluded that there was some support for the use of topical NSAIDs to relieve lateral elbow pain in the short term but insufficient evidence to recommend or discourage the use of oral NSAIDs (Green 2002). No data have directly compared topical with oral NSAIDs, and some data suggest that glucocorticoid injection may be more effective than oral NSAIDs in the short term. It is important to perform an update of this review to determine whether new data are available that may alter our conclusions.

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

To determine the benefits and harms of NSAIDs for patients with lateral elbow pain.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Criteria for considering studies for this review

 

Types of studies

All published randomised or quasi-randomised controlled trials (RCTs or CCTs) that compare NSAID therapy with another therapy (placebo or active, including non-pharmacological therapies) for lateral elbow pain were considered for inclusion.

Only trials published as a full article or available as a full trial report were considered for inclusion.

 

Types of participants

Inclusion in this review was restricted to trials with participants meeting the following criteria:

  • Adults >16 years of age.
  • No history of significant trauma or systemic inflammatory conditions such as rheumatoid arthritis.
  • Studies of various soft tissue diseases and pain due to tendonitis at all sites were included provided that the lateral elbow pain results were presented separately, or > 90% of participants in the trial had lateral elbow pain.

 

Types of interventions

All randomised controlled comparisons of NSAIDs versus placebo, or another intervention, or of varying types and dosages of topical or oral NSAIDs compared with each other were included, and comparisons were established according to intervention.

 

Types of outcome measures

Considerable variation has been noted in the outcome measures reported in clinical trials of interventions for pain. However, there is general agreement that outcome measures of greatest importance to patients should be considered.

The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) has published consensus recommendations for determining clinically important changes in outcome measures in clinical trials of interventions for chronic pain (Dworkin 2008). Reductions in pain intensity of ≥ 30% and ≥ 50% reflect moderate and substantial clinically important differences, respectively, and it is recommended that the proportion of patients who respond with these degrees of pain relief should be reported.

Continuous outcome measures in pain trials (such as mean change on a 100-mm visual analogue scale (VAS)) may not follow a Gaussian distribution. Often, a bimodal distribution is seen instead, where patients tend to report either very good or very poor pain relief (Moore 2010a). This creates difficulty in interpreting the meaning of average changes in continuous pain measures. For this reason, a dichotomous outcome measure (the proportion of participants reporting ≥ 30% pain relief) is likely to be more clinically relevant and was the primary efficacy measure in this review.

The original review determined that no trials had included a dichotomous outcome for pain, in keeping with the recognition that it has been the practice in most trials of interventions for chronic pain to report continuous measures only. We therefore also included the mean change in pain score as a secondary efficacy measure.

The pain state at the end of a clinical trial of an analgesic intervention, in contrast to measures of pain improvement, has also been recommended as a clinically relevant dichotomous outcome measure and was included as a secondary efficacy measure in this review (Moore 2010a). A global rating of treatment satisfaction, such as the Patient Global Impression of Change scale (PGIC), which provides an outcome measure that integrates pain relief, changes in function and side effects into a single, interpretable measure, is also recommended by IMMPACT, and was included as a secondary outcome measure (Dworkin 2008).

 

Primary outcomes

  • Primary endpoint to assess benefit: patient-reported pain relief of 30% or greater.
  • Primary endpoint to assess harm: number of withdrawals due to adverse events.

 

Secondary outcomes

  • Pain:

    • Patient-reported pain relief of 50% or greater.
    • Patient-reported global impression of clinical change (PGIC) in pain much or very much improved.
    • Proportion of patients achieving pain score below 30/100 mm on a visual analogue scale (VAS).
    • Mean change in pain score on a VAS or a numerical rating scale.

  • Function/disability as measured by disease-specific disability measures such as the Patient-Rated Tennis Elbow Evaluation questionnaire (PRTEE) (Rompe 2007).
  • Quality of life as measured by generic measures (such as components of the Short Form-36 (SF-36)) or disease-specific tools.
  • Grip strength (preferably pain-free maximum grip strength).
  • Patient's perception of overall effect as measured by a global rating of treatment satisfaction such as the Patient Global Impression of Change scale (PGIC).
  • Numbers and types of adverse events (AEs) and serious adverse events (SAEs, defined as AEs that are fatal, are life-threatening, or require hospitalisation).
  • Return to work.

The duration of trials of interventions for pain varies considerably. The efficacy of interventions, and the relative balance of benefits and harms, may vary according to the duration of the trial; therefore the combination of results from trials of different duration may represent a source of bias in systematic reviews (Moore 2010a).

For the purpose of this review, and if data were available, we planned to group endpoints into < 1 week, 1 to 6 weeks and > 6 weeks.

 

Search methods for identification of studies

 

Electronic searches

We searched the following databases for RCTs or CCTs using the search strategies detailed in the appendices on October 11, 2012:

  • Ovid MEDLINE 1946 to October 11, 2012 (Appendix 1).
  • Ovid EMBASE 1947 to October 1, 2012 (Appendix 2).
  • The Cochrane Central Register of Controlled Trials (CENTRAL) via The Cochrane Library, Issue 9 of 12, Sept 2012 (Appendix 3).
  • EbscoHost CINAHL 1982 to October 2012 (Appendix 4).
  • ISI Web of Science Science Citation Index Expanded (SCI-EXPANDED) 1899 to present (Appendix 5).

No language restrictions were applied.

 

Data collection and analysis

 

Selection of studies

Following identification of potential trials for inclusion by the previously outlined search strategy (TT), the methods sections of all identified trials were reviewed independently according to the predetermined criteria by two investigators (PP, TT). The investigator compiling the references (TT) decided on potentially relevant trials (based on whether the article was an RCT of an NSAID for lateral elbow pain), excluding those for which it was clear that the intervention and the population did not meet the inclusion criteria. Any disagreement in study selection was resolved by consensus or by discussion with a third and a fourth review author (RB and SG) as needed. Studies were translated into English where necessary.

 

Data extraction and management

Two review authors (PP and TT) independently extracted data using a standardised data extraction form for the newly included trials. Both authors also checked extracted data for the original studies in the review. RB checked all data extraction and helped to resolve any disagreements.

Raw data for outcomes of interest (means and standard deviations for continuous outcomes and number of events for dichotomous outcomes) were extracted where available from the published reports.

 

Assessment of risk of bias in included studies

All studies, including those previously included, were reviewed independently by two review authors (PP, TT) for assessment of risk of bias according to the guidelines put forth in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Assessment criteria included appropriateness of sequence generation, allocation concealment, blinding of participants, personnel and outcome assessments, management of incomplete outcome data, selective outcome reporting, and other sources of bias.

To determine the risk of bias of a study, for each criterion the presence of sufficient information and the likelihood of potential bias were evaluated. Each criterion was rated as low, high, or unclear (either lack of information or uncertainty over the potential for) risk of bias. In a consensus meeting, disagreements among the review authors were discussed and resolved. A third and a fourth review author (RB and SG) were available for assistance if no consensus had been reached.

 

Measures of treatment effect

The data were summarized in a meta-analysis only if clinical and statistical homogeneity was sufficient.

For continuous data, results were analysed as mean differences between the intervention and the comparator group (MD), with corresponding 95% confidence intervals (CIs). When outcomes were reported on non-standard scales, using differing units and methods of assessment (e.g. disability scales), a standardised mean difference was selected. The mean difference between the treated group and the control group is weighted by the inverse of the variance in the pooled treatment estimate.

When trial results were not normally distributed and so reported as median and range, the trial was not included in the meta-analysis, but results were presented in Additional Tables.

For dichotomous data, we calculated risk ratios (RRs) with corresponding 95% CIs.

Meta-analysis was facilitated by RevMan5 (RevMan2011). The statistics and the 95% CIs were presented for all outcomes.

For studies that included more than two intervention groups, making multiple pairwise comparisons between all possible pairs of intervention groups possible, we planned to include the same group of participants only once in the meta-analysis.

 

Dealing with missing data

For included trials where required data were not reported or could not be calculated, further details were requested of first authors. If no further details were provided, the trial was included in the review and was fully described, but was not included in the meta-analysis. An entry to that effect was made in the notes section of the Characteristics of included studies table.

 

Assessment of heterogeneity

Before a meta-analysis was performed, we assessed studies for clinical homogeneity with respect to type of therapy, control group, and outcomes. For any studies judged as clinically homogeneous, statistical heterogeneity was assessed using the I2 statistic (Deeks 2009) and the following as a rough guide for interpretation: 0% to 40% might not be important, 30% to 60% might represent moderate heterogeneity, 50% to 90% might represent substantial heterogeneity, and 75% to 100% might signify considerable heterogeneity.

In cases of considerable heterogeneity (defined as I2 ≥ 75%), we planned to explore the data further, including subgroup analyses, in an attempt to explain the heterogeneity.

 

Assessment of reporting biases

We planned to assess the potential for reporting bias using funnel plots if ≥10 studies were available. However, the lack of trials and the heterogeneity of outcomes in the included studies precluded this analysis.

 

Data synthesis

Where studies were sufficiently homogeneous that it remained clinically meaningful for data to be pooled, meta-analysis was performed using a random-effects model, regardless of the I2 results. Analysis was performed using Review Manager 5, and forest plots were produced for all analyses.

 

Sensitivity analysis

Two sensitivity analyses were planned and performed in the original review:

  • Trials published in languages other than English were excluded to assess the effect of possible publication bias. This sensitivity analysis was not performed in this update because of reduced concerns about publication and outcome assessment bias in non-English studies.
  • Trials in which the outcome assessor was not blinded were excluded to assess the possible effect of detection bias. This was not done in this update because it is recognised that all trials included in this review were at generally high risk of bias.

A third sensitivity analysis, not prespecified, was conducted to assess the effect of including skewed data in a single meta-analysis ( Analysis 1.1).

 

Presentation of key results

Key results for the main comparisons (topical NSAIDs vs placebo, oral NSAIDs vs placebo and oral NSAIDs vs glucocorticoid injection) are presented in the summary of findings tables. These tables provide key information concerning the quality of evidence, the magnitude of effect of the interventions examined, and the sum of available data on outcomes (patient-reported pain relief ≥ 30%, number of withdrawals due to adverse events, mean change in pain score on a VAS or a numerical rating scale, function, quality of life, participant's perception of overall effect and the total number of adverse events), as recommended by The Cochrane Collaboration (Schünemann 2011a); and an overall grading of the evidence related to each of the main outcomes using the GRADE approach (Schünemann 2011b).

In addition to the absolute and relative magnitude of effect for dichotomous outcomes provided in the summary of findings table, the number needed to treat to benefit (NNTB) or the number needed to treat to harm (NNTH) was calculated where appropriate from the control group event rate and the risk ratio (RR) using the Visual Rx number needed to treat (NNT) calculator (Cates 2008). For continuous outcomes, the NNT was calculated using the Wells calculator software available at the Cochrane Musculoskeletal Group (CMSG) editorial office (http://musculoskeletal.cochrane.org/). We assumed a minimal clinically important difference (MCID) of 1.5 points on a 10-point scale for pain, and 10 points on a 100-point scale for function or disability for input into the calculator.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Description of studies

 

Results of the search

The initial database search identified 49 potentially relevant records, of which 14 studies were included in the original review (Figure 1). The updated search identified 3002 records, of which 20 possibly eligible studies were assessed in full text. Fifteen trials (11/14 studies from the original review and 4 new studies identified from the updated search), reporting 17 comparisons, met the inclusion criteria.

 FigureFigure 1. Results of screening for studies that met inclusion criteria.

 

Included studies

A full description of each included study is given in the Characteristics of included studies table.

We identified four new trials that were not included in the previous review (Bäcker 2011; Polat 2011; Spacca 2005; Tsuyama 1979). Tsuyama 1979 was not identified in the previous search; and Bäcker 2011, Polat 2011 and Spacca 2005 were published after publication of the previous review.

Eight trials investigated topical NSAIDs. Five trials compared topical NSAIDs with placebo (Burnham 1998; Jenoure 1997; Schapira 1991; Spacca 2005; Tsuyama 1979). Four of these assessed the effect of topical diclofenac (Burnham 1998; Jenoure 1997; Schapira 1991; Spacca 2005), and one assessed the effect of topical indomethacin (Tsuyama 1979).

One trial compared topical NSAIDs with no treatment (both groups also received manipulative therapy) (Burton 1988), another trial compared topical diclofenac with locally applied leeches (Bäcker 2011) and another trial compared two different topical NSAIDs (iontophoresis of topical sodium diclofenac or sodium salicylate) (Demirtas 1998).

Six trials investigated oral NSAIDs: two trials compared oral NSAIDs with placebo (Hay 1999; Labelle 1997); one trial compared oral NSAIDs and bandaging with bandaging alone (Erturk 1997); three trials compared oral NSAIDs with glucocorticoid injection (Erturk 1997; Hay 1999; Saartok 1986); one trial compared oral NSAIDs with betahistine dihydrochloride (Polat 2011) and two trials compared two different oral NSAIDs (Adelaar 1987; Stull 1986).

No trials were identified that directly compared topical NSAIDs with oral NSAIDs.

Of the included trials, 13 were published in English, one in Italian (Jenoure 1997) and one in Japanese (Tsuyama 1979).

Only three trials followed participants for longer than 1 month: Bäcker 2011 for 45 days, Polat 2011 for six months and Hay 1999 for 12 months.

 

Excluded studies

We excluded three trials that were included in the original review (Primbs 1983; Percy 1981; Förster 1997). Primbs 1983 was excluded because the translated report clearly indicated that it was not an RCT; Percy 1981 was excluded because it was not clear what proportion of participants labelled as having tennis elbow had lateral versus medial epicondylitis; and Förster 1997 was excluded because the published paper was a subgroup analysis of an unpublished RCT. Only data for 48/116 participants who had acute epicondylitis (< 48 hours) due to squash, tennis, golf or other sporting activities were presented, and data were not presented separately for lateral elbow pain.

Reasons for exclusion of the other 51 excluded trials are outlined in the Characteristics of excluded studies table.

 

Risk of bias in included studies

The risk of bias of included studies is presented in the Characteristics of included studies table and is shown graphically across all trials and for individual trials in Figure 2 and Figure 3, respectively.

 FigureFigure 2. Risk of bias across all trials: review authors' judgements for each risk of bias item presented as percentages across all included trials.
 FigureFigure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included trial.

Most included trials were small, and risk of bias was generally high. Only three trials adequately described the method of sequence generation used (Bäcker 2011; Hay 1999; Labelle 1997), and only four trials adequately described allocation concealment (Bäcker 2011; Burnham 1998; Hay 1999; Labelle 1997). Blinding was not undertaken or was not clearly described in nine trials (Adelaar 1987; Bäcker 2011; Burton 1988; Demirtas 1998; Erturk 1997; Saartok 1986; Schapira 1991; Stull 1986; Tsuyama 1979); one trial blinded the single outcome assessor but most of the outcomes were patient-reported and participants were only partially blinded (NSAID or placebo or injection) (Hay 1999). Seven trials did not adequately address or did not adequately describe how incomplete data were managed (Adelaar 1987; Erturk 1997; Hay 1999; Labelle 1997; Saartok 1986; Schapira 1991; Stull 1986). No study demonstrated that it was free of selective outcome reporting, and all studies had other potential sources of bias.

 

Effects of interventions

See:  Summary of findings for the main comparison Topical NSAIDs compared to placebo for treating lateral elbow pain in adults;  Summary of findings 2 Oral NSAIDs compared to placebo for treating lateral elbow pain in adults;  Summary of findings 3 Oral NSAIDs compared to glucocorticoid injection for treating lateral elbow pain in adults

 

Topical NSAIDs versus placebo

Among five trials (204 participants) that assessed the effects of topical NSAIDs compared with placebo (Burnham 1998; Jenoure 1997; Schapira 1991, Spacca 2005; Tsuyama 1979), only three studies, with a total population of 153 participants, could be included in the meta-analysis (Jenoure 1997, Burnham 1998, Spacca 2005).

All three trials assessed the effects of topical diclofenac. No trial included a dichotomous measure of pain, and all included one or more continuous measures of pain. We pooled the final endpoint data, although timing varied (10 days (Spacca 2005); 3 weeks (Burnham 1998) and 4 weeks (Jenoure 1997)). No significant heterogeneity was noted, and the pooled MD favoured topical NSAIDs (RR -1.64, 95% CI -2.42 to -0.86;  Analysis 1.1). In other words, those in the topical NSAIDs group reported just over 1½ points (out of 10) less pain at the end of the trial compared with those who had received placebo, with an NNTB of 7 (95% CI 3 to 21) (see  Summary of findings for the main comparison). However when skewed data from two of the studies were excluded, the between-group difference was no longer statistically significant (-0.79, 95% CI -2.17 to 0.59; data not shown).

One trial (85 participants) found that significantly more participants reported fair, good or excellent effectiveness with topical NSAIDs versus placebo at 28 days (14 days of therapy) (RR 1.49, 95% CI 1.04 to 2.14;  Analysis 1.2) (Jenoure 1997).

One of the trials that could not be included in the meta-analysis because of inability to extract data also reported statistically significant benefits of diclofenac gel over placebo in terms of pain (Schapira 1991); the other reported statistically significant benefits of indomethacin gel for final degree of general improvement (Tsuyama 1979).

Very few adverse effects were reported in the topical NSAIDs or placebo group in any of the trials, and no between-group differences were apparent ( Analysis 1.3). No participants withdrew because of adverse effects. Burnham 1998 reported that one participant developed a rash at the site of application of diclofenac gel. Jenoure 1997 reported that tolerability of treatment was excellent in both treatment groups. One participant in each group developed a mild and transient skin rash, but in neither case was it necessary to discontinue treatment. Schapira 1991 reported no adverse effects, except for one participant in the diclofenac gel group who developed a transient mild and localised skin rash that did not necessitate discontinuation of the drug. Spacca 2005 reported no adverse events and no signs of cutaneous irritation and/or sensitisation in either group. Tsuyama 1979 did not report adverse effects separately for the lateral elbow pain group.

 

Topical NSAIDs and manipulative therapy versus manipulative therapy alone

Burton 1988 compared topical NSAIDs with no topical therapy in 17 participants, all of whom also received manipulative therapy. Improvements over time were seen in both groups, but no between-group differences were noted for degree of improvement in grip strength or pain on performing chosen function measured at three days, one week or three weeks (data not shown). The article did not report the presence or absence of adverse events.

 

Topical NSAID versus leech therapy

Bäcker 2011 compared a single treatment with two to four leeches (until they detached themselves; mean about 45 minutes) with topical diclofenac applied at least twice daily for 30 days. The authors reported a significant difference between groups favouring leeches in total pain score (derived as the sum of three single 100-mm VAS pain scores for pain at rest, in motion and during grip; scale 0 to 300 where higher score indicates increased pain) at 7 days (mean difference -49.0, 95% CI -82.9 to -15.1) but no between-group difference at 45 days (reported only graphically in the paper). Our analysis comparing pain scores at 7 and 45 days (with no adjustment for a higher pain score in the leech group at baseline) confirmed these findings ( Analysis 2.1). A statistically significant difference between groups favoured leech therapy at 45 days but not at 7 days for function ( Analysis 2.2), but no between-group differences were reported at either time point for quality of life ( Analysis 2.3) or grip strength ( Analysis 2.4). Of note, expectation of benefit was significantly greater in the leech group, but adjustment for this did not alter the results of analysis. Significantly fewer skin reactions were seen in the topical NSAID group (5% vs 50%, RR 0.10, 95% CI 0.01 to 0.71) ( Analysis 2.5).

 

One topical NSAID compared with another

Demirtas 1998 compared iontophoresis of topical sodium diclofenac or sodium salicylate in 40 participants and reported that diclofenac was more effective in reducing pain on pressure (RR 0.22, 95% CI 0.05 to 0.90); however, no between-group differences were noted for pain with wrist extension (RR 0.07, 95% CI 0.00 to 1.09), pain on using the wrist (RR 0.43, 95% CI 0.13 to 1.43) or pain at rest (RR 0.20, 95% CI 0.01 to 3.92) (data not shown).

 

Oral NSAIDs versus placebo

The data for two trials that compared oral NSAIDs with placebo could not be pooled because one of the trials presented median and interquartile ranges (Hay 1999) and neither reported pain as a dichotomous measure.

Labelle 1997 (128 participants) found that oral NSAIDs (75 mg diclofenac sodium twice daily for 28 days) were significantly better than placebo in improving pain (MD -13.9, 95% CI -23.2 to -4.6, 100 mm VAS) ( Analysis 3.1), but no significant between-group differences were noted in improvement in function (MD -3.30, 95% CI -13.13 to 6.53 ( Analysis 3.2), 100 mm VAS) or improvement in maximum pain-free grip strength (MD 2.60, 95% CI -0.85 to 6.05) ( Analysis 3.3) (see  Summary of findings 2).

The second trial, Hay 1999, reported no significant difference between NSAIDs and placebo with respect to their primary outcome of treatment success at 4 weeks (defined as complete recovery or some improvement) ( Analysis 3.4). Results for pain and function were reported as medians (interquartile ranges) at 4 weeks, 6 months and 12 months (see Additional  Table 1). Results appeared similar between groups at each time point, and a post hoc analysis performed by the trial authors, which dichotomised pain as 'better' (pain ≤ 3) or 'not better' (pain ≥ 4), also failed to demonstrate any significant between-group differences at 4 weeks, 6 months or 12 months (numbers (%) better at 4 weeks, 6 months and 12 months in the NSAIDs and placebo groups, respectively, were 25 (48) and 28 (50), 42 (81) and 47 (83) and 45 (85) and 44 (82)).

In this trial, the number of participants with pain on extension of the wrist or middle finger or grip strength > 300 mm Hg or the number of people disabled for eight items related to daily living did not differ between groups at any time point except for disability for opening doors, which favoured the NSAIDs group at 12 months (NSAIDs 1 (2%), placebo 9 (17%), P < 0.05) and was most likely a chance finding (Hay 1999). The number of participants taking time off paid employment was also not reported to differ between groups at 4 weeks or 12 months (NSAIDs 4 (10%) and 4 (10%), placebo 8 (17%) and 10 (21%), P > 0.05)).

Labelle 1997 reported a wide variety of adverse outcomes, but we could not extract numbers of participants with adverse events as these were not reported by participants. Investigators reported that oral NSAIDs significantly increased the risk of developing abdominal pain (RR 3.17, 95% CI 1.35 to 7.41) and diarrhoea (RR 1.92, 95% CI 1.08 to 3.41). One participant in the NSAIDs group withdrew from the study because of diarrhoea. Hay 1999 reported that oral NSAIDs were discontinued in four participants because of gastrointestinal side effects, and another participant who received NSAIDs had an allergic reaction characterised by oedema. No side effects were reported for those in the placebo group other than skin atrophy at the lateral epicondyle, which was reported to have occurred in three participants in the NSAIDs and placebo groups (number in each not specified), not all of whom had received a glucocorticoid injection (see later).

 

Oral NSAIDs and bandaging versus bandaging alone

Erturk 1997 incompletely reported their results. Mean improvements in pain, pain during resisted wrist extension and grip strength for each treatment group are reported in  Table 2. From the data presented, mean improvements favoured NSAID + bandaging for pain at rest and grip strength but not for pain with resisted wrist extension, but it was not possible to determine whether any of the differences were significant as the authors did not report standard deviations or any other measures of variance. Adverse event findings were not reported.

 

Oral NSAIDs versus glucocorticoid injection

Only two of the three trials that compared oral NSAIDs with glucocorticoid injection provided data for meta-analysis (Saartok 1986, Hay 1999). At 2 to 4 weeks, treatment success was not significantly different between groups (RR 0.74, 95% CI 0.43 to 1.26) ( Analysis 4.1).

However, Saartok 1986, the only trial that blinded participants to treatment allocation, did not find any between-group differences across a range of outcomes at 2 weeks, including pain and grip strength ( Analysis 4.2). Small sample size means that this study was most likely to have been underpowered.

On the other hand, Hay 1999 reported significant between-group differences favouring glucocorticoid for their primary outcome of treatment success at 4 weeks, and mean pain and function scores at 4 weeks (reported as medians and interquartile ranges; see Additional  Table 1) also appeared to favour glucocorticoid injection. Pain on extension of wrist or middle finger, grip strength > 300 mm Hg and number of people disabled for eight items related to daily living also favoured the glucocorticoid group at 4 weeks (data not shown). In a post hoc analysis that dichotomised pain as 'better' (pain ≤ 3) or 'not better' (pain ≥ 4), significantly more participants receiving glucocorticoid injection were better at 4 weeks compared with those given oral NSAIDs (41 (82%) vs 25 (48%), respectively, P < 0.05). However differences between groups could have been exaggerated because participants were unblinded with respect to whether or not they were receiving a glucocorticoid injection, but those who received tablets were blinded as to whether they were receiving NSAIDs or placebo tablets.

In the only trial that included longer-term outcomes, Hay 1999 found that some participants who received glucocorticoid injection seemed to have worsened at 6 months, with outcomes generally appearing to favour oral NSAIDs; by 12 months outcomes appeared generally similar between groups. The number of participants taking time off paid employment did not differ between groups at 4 weeks or 12 months (NSAIDs 4 (10%) and 4 (10%); glucocorticoid injection 5 (14%) and 5 (14%), P > 0.05).

Erturk 1997, which was also unblinded, found no significant differences between NSAIDs and glucocorticoid injection in mean improvement in pain at rest at 3 weeks, but results for pain with resisted wrist extension and grip strength appeared to favour the injection group ( Table 2). However, without standard deviations (SDs) it is not possible to determine whether these results were statistically significant.

Adverse event findings were not reported in two trials (Erturk 1997; Saartok 1986). In addition to the side effects that occurred in those exposed to oral NSAIDs, as described previously, Hay 1999 reported that local skin atrophy at the lateral epicondyle was observed in three trial participants (two at 6 months and one at 12 months), although only one had received a local injection of glucocorticoid (exact group not specified). As well, they reported that a minor increase in severity of pain lasted one day after injection, although the number of participants affected was not provided.

 

Oral NSAID versus a vasodilator

One trial compared naproxen with a central vasodilator, betahistine dihydrochloride (Polat 2011). Significantly less pain was reported at all follow-up time points (7 days, 3 months and 6 months) in the vasodilator group compared with the topical NSAIDs group ( Analysis 5.1) (data only at 7 days and 6 months shown). At 7 days, people in the vasodilator group had a pain score of 2.39 (SD 1.68) versus 6 (SD 1.38) in the topical NSAID group (MD 3.61, 95% CI 2.80 to 4.42) with a similar between-group difference reported at 3 and 6 months.

 

One oral NSAID compared with another

Diflunisal was compared with naproxen in two trials (Adelaar 1987; Stull 1986); the treatment regimens were similar and outcome data were pooled. No between-group differences were noted with respect to treatment success defined as either no remaining or improved symptoms (RR 1.19, 95% CI 0.88 to 1.62) ( Analysis 6.1) or as excellent, very good or good overall pain relief (RR 1.40, 95% CI 0.96 to 2.05) ( Analysis 6.2).

 Table 3 provides additional incomplete results from Adelaar 1987 for pain and functional capacity before and after treatment.

No differences were reported between groups with respect to numbers of participants experiencing any adverse effects (RR 3.65, 95% CI 0.65 to 20.66) ( Analysis 6.3), although more adverse events occurred in the diflunisal group overall. Four participants who received diflunisal in Stull 1986 reported adverse effects: two had nausea and one each reported vomiting and burning during urination, whereas one participant who received naproxen complained of feeling drowsy. Adelaar 1987 reported that one participant in the diflunisal group developed transient nausea and stomach cramps.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Summary of main results

Based upon data from fifteen trials, involving 759 trial participants, limited evidence was obtained from which firm conclusions could be drawn about the benefits or harms of topical or oral NSAIDs, and the following summary of results needs to be interpreted cautiously. Only two studies included in this review followed participants for longer than one month; consequently conclusions refer to short-term outcomes only. In addition none of the included studies reported the primary efficacy outcome of this review-patient-reported pain relief ≥ 30%-and the secondary efficacy outcomes were variably reported.

Eight of the included trials studied the effects of topical NSAIDs (301 participants). We found very low-quality evidence (from three trials with 153 participants) that topical NSAIDs may provide a small but significant benefit with respect to pain in the short term. In a pooled analysis of data from three of five placebo-controlled trials, topical NSAIDs provided an additional 1½ points out of 10 improvement in pain at the end of the trial period (10 days to 4 weeks) compared with placebo, with an NNTB of 7 (95% CI 3 to 21), although this finding was not robust to the potential impact introduced by the inclusion of skewed data from two of the three trials. Nevertheless one of these trials also found that topical NSAIDs were 1½ times more likely to result in treatment success in comparison with placebo (NNTB 4, 95% CI 2 to 25) ( Summary of findings for the main comparison), and both trials that could not be included in the meta-analysis also reported positive results.

Although the tolerability of topical NSAIDs was generally excellent, with no withdrawals due to adverse effects and no differences in numbers of adverse events compared with placebo, mild transient skin rash occurred in 3/204 (1.5%) participants who received topical NSAIDs and in one participant (0.5%) who received topical placebo.

One trial that compared topical NSAIDs and manipulative therapy with manipulative therapy alone failed to demonstrate any between-group differences in benefit, and an additional trial that compared iontophoresis of topical sodium diclofenac or salicylate reported that the diclofenac preparation provided better reduction of pain on pressure but no other between-group differences in outcome. One trial that compared topical NSAIDs with application of leeches reported better overall pain scores at 7 days but not at 45 days in the leech group and better function at 45 days but not at 7 days. Local skin reactions occurred less frequently with topical NSAIDs (5% of cases vs 50% in the leech group).

Six of the included trials studied the effects of oral NSAIDs (382 participants). Very low- to low-quality evidence from two trials was conflicting with respect to the benefit of oral NSAIDs ( Summary of findings 2). Only one of the two trials demonstrated that oral NSAIDs provided a small but statistically significantly greater improvement in pain compared with placebo, and the other trial reported no between-group differences in terms of pain, treatment success or time off paid employment. Neither trial demonstrated benefit in terms of function or maximum pain-free grip strength.

Very low-quality evidence from three trials that compared oral NSAIDs with glucocorticoid injection revealed conflicting results ( Summary of findings 3). Based upon two trials (126 participants) for which data could be pooled, no difference between treatments was noted with respect to treatment success in the short term (2 to 4 weeks). However one of these trials-the only one that blinded participants to treatment allocation but was underpowered-reported no between-group differences across a range of outcomes at 2 weeks, and the other trial, which did not blind participants and therefore could have overestimated any treatment benefit, reported significant differences favouring glucocorticoid injection over a range of outcomes at 4 weeks, favouring oral NSAIDs at 6 months and showing generally similar results by 12 months. A third trial that incompletely reported results described mixed results, with between-group differences favouring glucocorticoid injection for pain with resisted wrist extension and grip strength, but no mean improvement in pain at rest at 3 weeks; however, it is unclear whether these findings were significant because no variance measures were reported.

Use of oral NSAIDs was associated with increased risk of gastrointestinal side effects compared with placebo in one trial in the review. Another trial reported discontinuation of treatment in four participants taking NSAIDs due to gastrointestinal side effects and in another participant who developed an allergic reaction in response to oral NSAIDs.

Two trials that compared two different NSAIDs (naproxen and diflunisal) (62 participants) demonstrated no significant between-group differences with respect to benefit or numbers of adverse effects. Adverse effects in those who received diflunisal included nausea (n = 2), vomiting (n = 1), nausea and stomach cramps (n = 1) and burning during urination (n = 1); one participant who received naproxen developed drowsiness.

 

Overall completeness and applicability of evidence

Lateral elbow pain is a self-limiting but painful condition, and adequate pain relief is a high priority for people with the condition. Topical and oral NSAIDs continue to be commonly used to treat this condition, but the overall balance of benefits and harms associated with topical and oral NSAIDs remains a key issue.

Although most of the studies included in this review were performed between 1979 and 1999, and additional trials were published in 2005 and 2011, it is likely that results remain applicable to people with lateral elbow pain in the current era. Trial participants appeared typical of patients seen in routine care. Of note, we were unable to identify any published trials directly comparing topical with oral NSAIDs.

Outcomes reported in the trials varied widely, as did their method of measurement, and many trials inadequately reported important outcomes. For example, although seven trials have compared topical NSAIDs with placebo, we were able to draw conclusions about reduced pain and increased risk of adverse events based upon only three trials and treatment success based upon only one trial. In addition, none of the trials included a dichotomous measure of pain, as recommended by IMMPACT (Dworkin 2008). It is therefore likely that further trials will change these treatment effect estimates. None of the trials included a measure of quality of life, and less than half included a measure of function; therefore we were unable to draw any conclusions regarding these outcomes.

 

Quality of the evidence

Most of the thirteen trials included in this review were small (ten trials included 40 or fewer participants) and risk of bias was generally high, with only two trials adequately blinding trial participants. Methodological and reporting issues limited our ability to combine data.

At best, very low-quality evidence indicates benefit (in terms of pain relief and treatment success) of topical NSAIDs, and some patients may expect a transient mild rash with therapy. Evidence of the benefits of oral NSAIDs compared with both placebo and glucocorticoid injection was conflicting, and some patients may expect gastrointestinal and other side effects with oral NSAIDs.

Because of concerns about the potential risk of bias of all included trials and the risk of Type II error in many trials, further high-quality randomised controlled trials are needed to establish the true effects of both topical and oral NSAIDs for lateral elbow pain and their comparative effectiveness.

 

Potential biases in the review process

Upon completion of a thorough search of all major databases with no language restrictions, we believe that all relevant studies were identified. Two review authors assessed the trials for inclusion in the review and the risk of bias, and a third review author adjudicated whether there was any discrepancy. The biggest limitation of the review process was that many trials did not provide enough published data, or did not provide data in a form that could be extracted for meta-analysis.

 

Agreements and disagreements with other studies or reviews

Results of this updated review are in general agreement with those of our original review (Green 2002), although we excluded three trials erroneously included in the previous review and included an additional two trials. Our results are also in keeping with those of Boisaubert 2004-a review that found no additional trials on this topic.

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

 

Implications for practice

Limited evidence is available from which to draw firm conclusions about the benefits or harms of topical or oral NSAIDs in treating lateral elbow pain. Although data from five placebo-controlled trials suggest that topical NSAIDs may be beneficial in improving pain (for up to 4 weeks), non-normal distribution of data and other methodological issues preclude drawing of firm conclusions. Some people may expect a mild transient skin rash. Evidence of the benefits of oral NSAIDs is conflicting, although use of oral NSAIDs may result in gastrointestinal adverse effects in some people. No direct comparisons between oral and topical NSAIDs were available. Some trials demonstrated greater benefit from glucocorticoid injection than has been seen with NSAIDs in the short term, but this was not apparent in all studies and was not apparent by 6 months in the only study that included longer-term outcomes.

 
Implications for research

Further high-quality randomised controlled trials are needed to establish the true benefits and risks of both oral and topical NSAIDs for lateral elbow pain. Future trials should have adequate power for the research question posed, and should include strategies designed to minimise the potential for bias, including adequate randomisation methods, treatment allocation concealment and blinding of participants and outcome assessment. Development of a core set of outcomes for trials of lateral elbow pain would enhance this endeavour and improve our ability to synthesise the evidence. If the benefits of topical and/or oral NSAIDs become established, trials directly comparing topical with oral NSAIDs to determine which therapy has a better risk-benefit profile may be worthwhile.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

This update was partially supported by a fellowship granted to the first author by the SEA-ORCHID Project (www.seaorchid.org), funded by the Wellcome Trust (UK) and the Australian National Health and Medical Research Council (NHMRC). RB is partially supported by an Australian NHMRC Practitioner Fellowship.

Drs Les Barnsley, Stephen Hall, Nynke Smidt, and Willem Assendelft as well as Millicent White, were authors of the original review.

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
Download statistical data

 
Comparison 1. Topical NSAIDs versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pain at endpoint of study (10 days to 4 weeks) on 10cm VAS (10=maximum pain)3153Mean Difference (IV, Random, 95% CI)-1.64 [-2.42, -0.86]

 2 Treatment success (proportion reporting fair, good or excellent overall effectiveness of treatment) at 28 days (14 days of therapy)1Risk Ratio (M-H, Random, 95% CI)Totals not selected

 3 Adverse events3153Risk Ratio (M-H, Random, 95% CI)1.55 [0.20, 12.14]

 
Comparison 2. Topical NSAID versus leech therapy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Overall pain (0 to 300mm VAS)1Mean Difference (IV, Random, 95% CI)Totals not selected

    1.1 7 days
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    1.2 45 days
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 2 DASH1Mean Difference (IV, Random, 95% CI)Totals not selected

    2.1 7 days
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    2.2 45 days
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 3 Quality of life- physical1Mean Difference (IV, Random, 95% CI)Totals not selected

    3.1 7 days
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    3.2 45 days
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 4 Maximum peak grip strength1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 7 days
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 45 days
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Adverse events- local skin reaction1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 3. Oral NSAIDs versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Improvement in pain (100mm vertical VAS) at endpoint of study (28 days)1Mean Difference (IV, Random, 95% CI)Totals not selected

 2 Improvement in function (100mm vertical VAS at endpoint of study (28 days)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 3 Improvement in pain-free maximum grip strength (kg) at endpoint of study (28 days)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 4 Treatment success (complete recovery or improved) at 4 weeks1Risk Ratio (M-H, Random, 95% CI)Totals not selected

 
Comparison 4. Oral NSAIDs versus glucocorticoid injection

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Treatment success (complete recovery or improved) at 2 or 4 weeks2126Risk Ratio (M-H, Random, 95% CI)0.74 [0.43, 1.26]

 2 Change in grip strength (kPa)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 
Comparison 5. Oral NSAIDs versus vasodilator

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pain (0 to 10 VAS)1Mean Difference (IV, Random, 95% CI)Totals not selected

    1.1 10 days
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    1.2 6 months
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 
Comparison 6. Oral Diflusinal versus oral Naproxen

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Treatment success defined as no remaining symptoms or improved at 2 weeks256Risk Ratio (M-H, Random, 95% CI)1.19 [0.88, 1.62]

 2 Treatment success defined as excellent, very good or good overall pain relief at 2 weeks256Risk Ratio (M-H, Random, 95% CI)1.40 [0.96, 2.05]

 3 Number of participants experiencing any adverse effects256Risk Ratio (M-H, Random, 95% CI)3.65 [0.65, 20.66]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Appendix 1. MEDLINE search strategy

1. exp Tendinopathy/

2. exp Tendon Injuries/

3. (Tendinitis or Tendinosis or Tendonitis).tw.

4. or/1-3

5. Elbow Joint/

6. elbow$.tw.

7. 5 or 6

8. exp Pain/

9. pain$.tw.

10. 8 or 9

11. 7 and (4 or 10)

12. Tennis Elbow/

13. tennis elbow.tw.

14. common extensor origin.tw.

15. (epicondylalgia or epicondylitis).tw.

16. or/11-15

17. randomized controlled trial.pt.

18. controlled clinical trial.pt.

19. randomized.ab.

20. placebo.ab.

21. drug therapy.fs.

22. randomly.ab.

23. trial.ab.

24. groups.ab.

25. or/17-24

26. (animals not (humans and animals)).sh.

27. 25 not 26

28. 16 and 27

 

Appendix 2. EMBASE search strategy

1. exp Tendinitis/

2. exp Tendon Injury/

3. (Tendinitis or Tendinosis or Tendonitis).tw.

4. or/1-3

5. Elbow/

6. elbow$.tw.

7. 5 or 6

8. exp pain/

9. pain$.tw.

10. 8 or 9

11. 7 and (4 or 10)

12. tennis elbow/

13. tennis elbow.tw.

14. common extensor origin.tw.

15. (epicondylalgia or epicondylitis).tw.

16. or/11-15

17. (random$ or placebo$).ti,ab.

18. ((single$ or double$ or triple$ or treble$) and (blind$ or mask$)).ti,ab.

19. controlled clinical trial$.ti,ab.

20. RETRACTED ARTICLE/

21. or/17-20

22. (animal$ not human$).sh,hw.

23. 21 not 22

24. 16 and 23

 

Appendix 3. CENTRAL search strategy

#1             MeSH descriptor Tendinopathy explode all trees

#2             MeSH descriptor Tendon Injuries explode all trees

#3             (Tendinitis or Tendinosis or Tendonitis):ti,ab

#4             (#1 OR #2 OR #3)

#5             MeSH descriptor Elbow Joint, this term only

#6             elbow*:ti,ab

#7             (#5 OR #6)

#8             MeSH descriptor Pain explode all trees

#9             pain*:ti,ab

#10          (#8 OR #9)

#11          (#7 AND ( #4 OR #10 ))

#12          MeSH descriptor Tennis Elbow, this term only

#13          "tennis elbow":ti,ab

#14          epicondylitis:ti,ab

#15          "common extensor origin":ti,ab

#16          epicondylalgia:ti,ab

#17          (#11 OR #12 OR #13 OR #14 OR #15 OR #16)

 

Appendix 4. CINAHL search strategy

S1 (MH "Tendinopathy+")
S2 (MH "Tendon Injuries+")

S3 TI Tendinitis OR AB Tendinitis

S4 TI Tendinosis OR AB Tendinosis

S5 TI Tendonitis OR AB Tendonitis

S6 S1 or S2 or S3 or S4 or S5

S7 (MH "Elbow Joint")
S8 TI elbow* OR AB elbow*

S9 S7 or S8
S10 (MH "Pain+")
S11 TI Pain* OR AB Pain*

S12 S10 or S11
S13 S9 and (S6 OR S12)

S14 (MH "Tennis Elbow")

S15 TI tennis elbow OR AB tennis elbow

S16 TI epicondylitis OR AB epicondylitis 

S17 TI common extensor origin OR AB common extensor origin

S18 TI epicondylalgia OR AB epicondylalgia

S19 S13 or S14 or S15 or S16 or S17 or S18

S20 (MH "Clinical Trials+")

S21 PT clinical trial
S22 TI clinical* trial* or AB clinical* trial* Search modes - Boolean/Phrase

S23 TI singl* blind* or TI singl* mask* or TI doub* blind* or TI doubl* mask* or TI trebl* blind* or TI trebl* mask* or TI tripl* blind* or TI tripl* mask* Search modes - Boolean/Phrase S24 AB singl* blind* or AB singl* mask* or AB doub* blind* or AB doubl* mask* or AB trebl* blind* or AB trebl* mask* or AB tripl* blind* or AB tripl* mask*  

S25 TI Randomi?ed control* trial* or AB Randomi?ed control* trial*

S26 (MH "Random Assignment")

S27 TI Placebo* or AB Placebo*

S28 (MH "Placebos")
S29 (MH "Quantitative Studies")

S30 TI Allocat* random* or AB Allocat* random*
S31 S20 or S21 or S22 or S23 or S24 or S25 or S26 or S27 or S28 or S29 or S30

S32 S19 and S31

 

Appendix 5. ISI Web of Science search strategy

#1 TS=(tennis elbow or tendinitis or tendonitis tendinosis or (elbow* and pain*) or epicondylitis or common extensor origin or epicondylalgia)

#2 TS=(trial* or random* or placebo* or control* or double or treble or triple or blind* or mask* or allocat* or prospective* or volunteer*or comparative or evaluation or follow-up or followup)

#3 #1 AND #2

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Last assessed as up-to-date: 11 October 2012.


DateEventDescription

13 February 2013New citation required but conclusions have not changedNew authors; substantial changes to methodology including outcomes as recommended by IMMPACT, risk of bias tables, and summary of findings tables.

11 October 2012New search has been performedNew search conducted 11 October 2012, and four new trials were added to the review. Fifteen trials are included in this review update; 11/14 trials from the first review, plus four trials identified from the updated search. Tsuyama 1979 was not identified in the previous search; Spacca 2005, Bäcker 2011, and Polat 2011 were published after publication of the previous review.

The three trials that were included in the original review but excluded in the update were Primbs 1983 (excluded because it was clearly not an RCT in the translated report); Percy 1981 (excluded because it was not clear what proportion of participants labelled as having tennis elbow had lateral versus medial epicondylitis); and Förster 1997 (excluded because the published paper was a subgroup analysis of an unpublished RCT).

28 October 2009AmendedL Barnsley and S Hall contributed content expertise for the original review.



 

History

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Protocol first published: Issue 3, 1999
Review first published: Issue 2, 2002


DateEventDescription

11 June 2009New citation required but conclusions have not changedSubstantive amendment

11 June 2009AmendedConverted to new review format.



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

All authors were responsible for all components of the review, including selection of trials for the update of the review, appraisal of the risk of bias of included trials, extraction and analysis of data, interpretation of the results and writing of the manuscript.

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Internal sources

  • Thai Cochrane Network, Thailand.
  • Australasian Cochrane Centre, Australia.

 

External sources

  • The Wellcome Trust, UK and the Australian National Health and Medical Research Council, through funding of the SEA-ORCHID Project, Australia.

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

In the original review we limited inclusion of trials to those with study participants who had lateral elbow pain of greater than 3 weeks' duration but removed this criterion in the updated review, as NSAIDs are most commonly used for acute symptoms.

We updated the outcomes that were considered in this review according to the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), which has published consensus recommendations for determining clinically important changes in outcome measures in clinical trials of interventions for chronic pain (Dworkin 2008).

We excluded three trials that were included in the original review (Förster 1997; Percy 1981; Primbs 1983). Förster 1997 was excluded because the published paper was a subgroup analysis of an unpublished RCT. Only data for 48/116 participants who had acute epicondylitis (< 48 hours) due to squash, tennis, golf or other sporting activities were presented, and data were not presented separately for lateral elbow pain. Percy 1981 was excluded because it was not clear what proportion of participants labelled as having tennis elbow had lateral versus medial epicondylitis. Primbs 1983 was excluded because it clearly was not an RCT, as described in the translated report.

Changes to the risk of bias table and sensitivity analysis sections in this updated review reflect advances in systematic review methodology.

In the original review we performed a sensitivity analysis excluding trials published in languages other than English. We did not perform this sensitivity analysis in this update because of reduced concerns about publication and outcome assessment bias in non-English studies.

We corrected some errors in the previous analyses. For example, in the original review, Burton 1988 was listed under topical NSAIDs versus placebo, but review of the article clearly revealed that the trial compared topical NSAIDs with no topical treatment, although both groups also received manipulative therapy.

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. Additional references
  23. References to other published versions of this review
Adelaar 1987 {published data only}
  • Adelaar R, Maddy L, Emroch L. Diflunisal versus naproxen in the management of mild to moderate pain associated with epicondylitis. Advances in Therapy 1987;4(6):317-27.
Bäcker 2011 {published data only}
  • Bäcker M, Ludtke R, Afra D, Cesur O, Langhorst J, Fink M, et al. Effectiveness of leech therapy in chronic lateral epicondylitis: a randomized controlled trial. Clinical Journal of Pain 2011;27(5):442-7.
Burnham 1998 {published data only}
Burton 1988 {published data only}
  • Burton A. A comparative trial of forearm strap and topical anti-inflammatory as adjuncts to manual therapy in tennis elbow. Manual Medicine 1988;3:141-3.
Demirtas 1998 {published data only}
Erturk 1997 {published data only}
  • Erturk H, Celiker R, Sivri A, Cetin A, Cindas A. The efficacy of different treatment regiments that are commonly used in tennis elbow. Journal of Rheumatology and Medical Rehabilitation 1997;8:298-301.
Hay 1999 {published data only}
  • Hay E, Paterson S, Lewis M, Hosie G, Croft P. Pragmatic randomised controlled trial of local corticosteroid injection and naproxen for treatment of lateral epicondylitis of elbow in primary care. BMJ 1999;319:964-8.
Jenoure 1997 {published data only}
  • Jenoure P, Rostan A, Gremion G, Meier J, Grossen R, Bielinki R, et al. Multi-centre, double-blind, controlled clinical study on the efficacy of diclofenac epolamine tissugel plaster in patients with epicondylitis. Medicina Dello Sport 1997;50:285-92.
Labelle 1997 {published data only}
Polat 2011 {published data only}
  • Polat A, Ekinci O, Terzioglu B, Canbora M, Muftuoglu T, Gorgec M. Treatment of lateral epicondylitis using betahistine dihydrochloride. Journal of Musculoskeletal Pain 2011;19(4):201-6.
Saartok 1986 {published data only}
  • Saartok T, Eriksson E. Randomized trial of oral naproxen or local injection of betamethasone in lateral epicondylitis of the humerus. Orthopaedics 1986;2:191-4.
Schapira 1991 {published data only}
  • Schapira D, Linn S, Scharf Y. A placebo-controlled evaluation of diclofenac diethylamine salt in the treatment of lateral epicondylitis of the elbow. Current Therapeutic Research 1991;49(2):162-8.
Spacca 2005 {published and unpublished data}
  • Spacca G, Cacchio A, Forgacs A, Monteforte P, Rovetta G. Analgesic efficacy of a lecithin-vehiculated diclofenac epolamine gel in shoulder periarthritis and lateral epicondylitis: a placebo-controlled, multicenter, randomized, double-blind clinical trial. Drugs Under Experimental & Clinical Research 2005;31(4):147-54.
Stull 1986 {published data only}
  • Stull P, Jokl P. Comparison of diflunisal and naproxen in the treatment of tennis elbow. Clinical Therapeutics 1986;9(Suppl C):62-6.
Tsuyama 1979 {published data only}
  • Tsuyama N, Nichikawa K, Tsujimoto M, Miyanaga Y, Mizushima H, Nakajima A. Clinical evaluation of non-steroidal anti-inflammation/analgesics for external use - Indomethacin ointment - in the orthopaedic field. Clinical Evaluation 1979;7:285-309.

References to studies excluded from this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. Additional references
  23. References to other published versions of this review
Abbott 1980 {published data only}
  • Abbott C, Bouchier-Hayes T, Hunt H. A comparison of the efficacy of naproxen sodium and a paracetamol/dextropropoxyphene combination in the treatment of soft-tissue disorders. British Journal of Sports Medicine 1980;14:213-8.
Auvinet 1995 {published data only}
  • Auvinet B, Crielaard J, Manteuffel GE, Müller P, Multicenter Piroxicam FDDF European Study Group . A double-blind comparison of fast dissolving dosage form and diclofenac enteric-coated tablets in the treatment of patients with acute musculoskeletal disorders. Current Therapeutic Research 1995;56:1142-53.
Baskurt 2003 {published data only}
  • Baskurt F, Ozcan A, Algun C. Comparison of effects of phonophoresis and iontophoresis of naproxen in the treatment of lateral epicondylitis. Clinical Rehabilitation 2003;17(1):96-100.
Bolten 1991 {published data only}
  • Bolten W. Felbinac gel for treatment of localized extra-articular rheumatic diseases - a multicenter, placebo controlled, randomized study [Felbinac-Gel zur Behandlung lokalisierter extraartikularer rheumatischer Beschwerden - eine multizentrische, placebokontrollierte, randomisierte studie]. Zeitschrift für Rheumatologie 1991;50:109-13.
Bono 1983 {published data only}
  • Bono RF, Finkel S, Goodman H, Hanna C. A multicenter, double-blind comparison of oxaprozin, phenylbutazone, and placebo therapy in patients with tendinitis and bursitis. Clinical Therapeutics 1983;6(1):79-85.
Boussina 1983 {published data only}
  • Boussina I, Gunthner W, Marti Masso R. Double-blind multicenter study comparing meclofenamate sodium with indomethacin and placebo in the treatment of extra-articular rheumatic disease. Arzneimittel-Forschung 1983;33(4A):649-52.
Buckwalter 1995 {published data only}
  • Buckwalter JA. Pharmacological treatment of soft-tissue injuries. The Journal of Bone and Joint Surgery 1995;77A(12):1902-14.
Burgos 2001 {published data only}
  • Burgos A, Busquier MP, Reino JG, Ferreiro JL, Navarro F, Valverde J, et al. Double-blind, double-dummy comparative study of local action transcutaneous flurbiprofen (flurbiprofen LAT) versus piketoprofen cream in the treatment of extra-articular rheumatism. Clinical Drug Investigation 2001;21(2):95-102.
Castro DeTolosa 1994 {published data only}
  • Castro De Tolosa E, Bueno Pereira P, Barreto Reis J, Hideo Hori A. Comparative evaluation of two non-steroidal anti-inflammatory drugs in patients with acute tendinitis or bursitis. Arquivos Brasileiros de Medicina 1994;68:203-7.
Commandre 1983 {published data only}
  • Commandre F. Double-blind comparative study of piroxicam and indomethacin in acute locomotor affections linked with sports activity. European Journal of Rheumatology and Inflammation 1983;6:113-8.
Commandre 1993 {published data only}
  • Commandre F, Zakarian H, Corriol-Rohou S. Comparison of the analgesic effects of topical niflumic acid gel versus piroxicam gel in the treatment of musculoskeletal disorders. Current Therapeutic Research, Clinical and Experimental 1993;53:113-21.
Dreiser 1988 {published data only}
  • Dreiser RL. Clinical trial of efficacy and tolerability of topical ibuprofen in the treatment of tendinitis. Le Journal International de Medicine 1988;119:70-3.
Dreiser 1991 {published data only}
  • Dreiser R, Ditisheim A, Charlot J, Lopez A. A double-blind, placebo controlled study of niflumic acid gel in the treatment of acute tendinitis. European Journal of Rheumatology and Inflammation 1991;11:38-45.
Fauchald 1978 {published data only}
  • Fauchald N, Ronning F, Saxegaard E, Sjolyst R. Naproxen and phenylbutazone in acute tendinitis: a multi-center double-blind comparison. Tidsskrift for Den Norske Laegeforening 1978;98:1004-6.
Fiszman 1985 {published data only}
  • Fiszman P, Perpetuo J, Sidi A. Ro 12-0068 (Tenoxicam) in the treatment of extra-articular inflammatory processes. European Journal of Rheumatology and Inflammation 1985;8:15-20.
Förster 1997 {published data only}
  • Förster KK, Schmid K, Reichelt A. Sports-induced acute epicondylitis of the elbow and conservative therapy [Sportbedingte akute epikondylitis des ellenbogens und ihre konservative therapie]. Sportverletz Sportschaden 1997;11:16-20.
Furberg 1985 {published data only}
  • Furberg B, Lerner A, Nystrom B, Rosen M, Willig P. Antiphlogistics in acute inflammatory conditions in the soft tissues of the musculo-skeletal system - a double blind comparison of diclofenac and indomethacin. Current Therapeutic Research, Clinical & Experimental 1985;38(3):523-7.
Gallacchi 1990 {published data only}
  • Gallacchi G, Mautone G, Lualdi P. Painful inflammatory conditions: topical treatment with diclofenac hydroxyethylpyrrolidine ((R)Flector gel 1%). Clinical Trials Journal 1990;27(1):58-64.
Geiger 1995 {published data only}
  • Geiger L, Elsasser R, Bias P, Haag RF. Placebo-controlled clinical study with Dolobene (R) gel in the treatment of epicondylitis. Deutsche Zeitschrift fur Sportmedizin 1995;46(4):221-7.
Ginsberg 1994 {published data only}
  • Ginsberg F, Famaey J. Double-blind, randomized cross over study of the percutaneous efficacy and tolerability of a topical indomethacin spray versus placebo in the treatment of tendinitis. Journal of Musculoskeletal Pain 1994;2(1):127-8.
Goldberg 1985 {published data only}
  • Goldberg D, Rondier J, Oberlin F, Cayla J, Parier J. Preliminary study of the local injection of superoxide dismutase in epicondylitis [Etude preliminarie de l'injection locale de superoxyde dismutase au cours des epicondylites]. Revue du Rhumatisme et des Maladies Osteo-Articulaires 1985;52(4):291.
Grossi 1986 {published data only}
  • Grossi E, Monza GC, Pollavini S, Bona L. NSAID ionisation in the management of soft-tissue rheumatism: role played by the drug, electrical stimulation and suggestion. Clinical and Experimental Rheumatology 1986;4(3):265-7.
Gui 1982 {published data only}
  • Gui L, Pellacci F, Ghirardini G. Use of ibuprofen cream in ambulatory orthopaedic patients: double-blind comparison with placebo. Clinica Terapeutica 1982;101:363-9.
Halle 1986 {published data only}
  • Halle J, Franklin RJ, Karalfa L. Comparison of four treatment approaches for lateral epicondylitis of the elbow. Journal Orthopaedic Sports Physical Medicine 1986;8(2):62-9.
Hofman 2000 {published data only}
  • Hofman J, Nasswetter G, Cayetti LM. Lysine clonixinate gel in soft tissue injuries: controlled randomized prospective double-blind clinical trial with diclofenac. Presna Medica Argentina 2000;87:513-20.
Hughes 1969 {published data only}
Jakobsen 1988 {published data only}
  • Jakobsen T, Petersen L, Christiansen S, Haarbo J, Munch M, Larsen P, et al. Double-blind comparative study of tenoxicam, piroxicam, and placebo in acute soft-tissue injuries. Current Therapeutic Research, Clinical and Experimental 1988;44(4):516-27.
Jakobsen 1991 {published data only}
  • Jakobsen T, Petersen L, Christiansen S,  Haarbo J,  Munch M,  Larsen PB,  et al. Should athletic injuries be treated with non-steroidal anti-rheumatic agents (NSAID)?. Ugeskrift for Laeger 1991;153:2003-5.
Jensen 2001 {published data only}
  • Jensen B, Bliddal H, Danneskiold-Samsoe B. Comparison of two different treatments for lateral epicondylitis. Ugeskrift for Laeger 2001;163(10):1427-31.
Karinen 1999 {published data only}
  • Karinen P, Kemola T, Pienimaki T, Koivukangas P, Vanharanta H. Economic evaluation of two different treatments of the tennis elbow. 15th Annual Meeting of the International Society of Technology Assessment in Health Care. 1999.
Kneer 1994 {published data only}
  • Kneer W, Kuhnau S, Bias P,  Haag RF. Dimethylsulfoxide (DMSO) gel for the treatment of acute tendinopathy. A multicentre placebo-controlled randomized study. Fortschritte der Medizin 1994;112:142-6.
Kroll 1989 {published data only}
  • Kroll M, Wiseman R, Guttadauria M. A clinical evaluation of piroxicam gel: an open comparative trial with diclofenac gel in the treatment of acute musculoskeletal disorders. Clinical Therapeutics 1989;11:382-91.
Lecomte 1994 {published data only}
  • Lecomte J, Buyse H, Taymans J, Monti T. Treatment of tendinitis and bursitis: a comparison of nimesulide and naproxen sodium in a double-blind parallel trial. European Journal of Rheumatology and Inflammation 1994;14:29-32.
Lopez 1997 {published data only}
  • Lopez A, Auguste P, Maurandy P, Tamisier S, Wullaert P, Martin C, et al. Efficacy and safety of oral niflumic acid in the treatment of acute tendinitis of the limbs (a multicenter, randomised, double-blind, placebo-controlled trial). Les Semaines des Hôpitaux Thérapeutique 1997;73:953-60.
McGuinness 1969 {published data only}
  • McGuinness BW, Lloyd-Jones M, Fowler PD. A double-blind comparative trial of 'parazolidin' and paracetamol. British Journal of Clinical Practice 1969;23(11):542-5.
Meloni 1995 {published data only}
  • Meloni P, Demuro G, Cara L,  Garau D,  Uras G,  Suddu L. Evaluation of the effectiveness and tolerability of MED 15 vs piroxicam in patients with acute epicondylitis. Clinica Terapeutica 1995;146(6-7):453-6.
Menkes 1990 {published data only}
  • Menkes C, Laoussadi S, Kac-Ohana, Lasserre O. Controlled trial of injectable diclofenac in mesotherapy for the treatment of tendinitis [Essai controle du diclofenac injectable en mesotherapie dans le traitement des tendinites]. Revue du Rhumatisme et des Maladies Osteo-Articulaires 1990;57:589-91.
Nilsson 2012 {published data only}
  • Nilsson P, Baigi A, Sward L, Moller M, Mansson J. Lateral epicondylalgia: a structured programme better than corticosteroids and NSAID. Scandinavian Journal of Occupational Therapy 2012;19(5):404-10.
Percy 1981 {published data only}
Primbs 1983 {published data only}
Ritchie 1996a {published data only}
  • Ritchie LD, Johnson N. A willingness to pay analysis: comparison of the patient preference for topical flurbiprofen local action cutaneous patches and piroxicam gel. British Journal of Medical Economics 1996;10:291-302.
Ritchie 1996b {published data only}
Rosenthal 1982 {published data only}
  • Rosenthal M. The application of an extract of human placenta in the treatment of rheumatic affections. International Journal of Tissue Reactions 1982;4(2):147-51.
Rosenthal 1984 {published data only}
Saggini 1997 {published data only}
  • Saggini R, Zoppi M, Vecchiet F,  Gatteschi L,  Obletter G,  Giamberardino MA. Comparison of electromotive drug administration with ketorolac or placebo in patients with pain from rheumatic disease. Clinical Therapeutics 1997;18(6):1169-74.
Saudan 1977 {published data only}
Schorn 1986 {published data only}
Seligra 1990 {published data only}
Sileghem 1991 {published data only}
  • Sileghem A, Verstraeten A, Dequeker J. Double-blind, randomised, parallel-group study of the efficacy and safety of poglumetacin and naproxen in periarthritis of the shoulder or elbow. Current Therapeutic Research 1991;1:93-100.
Thorling 1990 {published data only}
Turbio 1993 {published data only}
  • Turbio F, Ishida A, Laredo F. Etodolac versus diclofenac in acute tendinitis and bursitis. Arquivos Brasilieiros de Medicina 1993;67:217-23.
Vecchini 1984 {published data only}
  • Vecchini L, Grossi E. Ionisation with diclofenac sodium in rheumatic disorders: a double blind placebo controlled trial. Journal of International Medical Research 1984;12:346-50.
Venerando 1973 {published data only}
  • Venerando A, Santilli G. Use of 2-(4-isobutylphenyl)-propionic acid (brufen) in the treatment of some diseases of athletes [Sull'impiego dell'acido 2-(4-isobutilfenil)-propionico (Brufen) nel trattamento di alcune atlopatie]. Minerva Medica 1973;64(48):2537-9.
Wiseman 1987 {published data only}
  • Wiseman R, Sodergren J, Guttadauria M, Ryan A. Treatment of acute musculoskeletal disorders with piroxicam: results of a double-blind multicenter comparison with naproxen. Current Therapeutic Research, Clinical and Experimental 1987;42:974-87.

Additional references

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. Additional references
  23. References to other published versions of this review
Alizadehkhaiyat 2007
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