Current evidence suggests that platelet-rich plasma (PRP) injections may be more effective than hyaluronic acid (HA) for long-term pain relief and functional improvement in patients with knee osteoarthritis. Of note, no differences were reported in the risk of adverse events for PRP compared to HA. These findings should be interpreted with caution, since the review had substantial methodological weaknesses meaning that relevant studies may have been missed, and reviewer error and bias could not be ruled out. Further well-designed and high-quality studies focussing on optimal dosage, timing interval and injection frequency across different stages of knee osteoarthritis are needed.
Overall summary High risk of bias in the review
The search strategy was not reported, meaning it was not possible to assess if this was adequate; ultimately, relevant studies may have been missed. No information was provided on the number of reviewers involved in the study selection process, meaning reviewer error and bias could not be ruled out. Heterogeneity was high for some analyses. Robustness of the findings was not addressed in the synthesis.
|A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4?||Probably no|
|B. Was the relevance of identified studies to the review's research question appropriately considered?||Probably yes|
|C. Did the reviewers avoid emphasizing results on the basis of their statistical significance?||Probably yes|
|Risk of bias in the review||High|
|Number of studies||15|
|Number of participants||1,314|
|Last search date||April 2018|
|Objective||To compare platelet-rich plasma versus hyaluronic acid in patients with knee osteoarthritis.|
|Population||Patients with knee osteoarthritis (KOA).|
|Interventions||Platelet-rich plasma (PRP) injections.|
|Comparator||Hyaluronic acid (HA) injections.|
|Outcome||The Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analogue scale (VAS), International Knee Documentation Committee (IDKC), and Lequesne Index scores and adverse events.|
|Study design||Randomised controlled trials (RCTs).
Case reports, letters and editorials were excluded.
In terms of WOMAC pain scores, pooled analyses reported no difference in WOMAC pain score for platelet-rich plasma (PRP) compared to hyaluronic acid (HA) at one month (mean difference [MD] -0.19, 95% confidence interval [CI] -0.65 to 0.27; 3 studies, n=222 patients) or at three months (MD -0.31, 95% CI -1.16 to 0.54; 4 studies, n=267 patients). However, pooled analyses reported more pain relief with PRP compared to HA at six months (MD -1.24, 95% CI -1.94 to -0.53; 6 studies, n=533 patients) and 12 months (MD -1.75, 95% CI -2.50 to -1.01; 5 studies, n=450 patients).
In terms of WOMAC functional scores, pooled analyses reported no difference in WOMAC functional scores for PRP compared to HA at one month (MD -2.35, 95% CI -5.28 to 0.57; 2 studies, n=122 patients); however, pooled analyses reported better WOMAC function for PRP compared to HA at three months (MD -1.92, 95% CI -2.57 to -1.27; 4 studies, n=168 patients), six months (MD -3.71, 95% CI - 7.21 to -0.22; 5 studies, n=434 patients) and 12 months (MD -8.90, 95% CI -14.82 to -2.99; 4 studies, n=351 patients).
In terms of visual analogue scale (VAS) pain scores, pooled analyses reported no difference in VAS pain scores for PRP compared to HA at one month (MD 0.01, 95% CI -0.13 to 0.15; 3 studies, n=143 patients), three months (MD -0.20, 95% CI -0.64 to 0.24; 4 studies, n=180 patients) or six months (MD -3.62, 95% CI -7.49 to 0.26; 4 studies, n=290 patients); however, pooled analyses reported an improvement in VAS pain scores for PRP compared to HA at 12 months (MD -4.95, 95% CI -7.83 to -2.06; 3 studies, n=221 patients).
In terms of International Knee Documentation Committee (IDKC) orthopaedic scores, pooled analyses reported no difference in IDKC score for PRP compared to HA at 2 months (MD 0.29, 95% CI -3.44 to 4.02; 2 studies, n=292 patients); however, pooled analysis reported an improvement in IDKC score for PRP compared to HA at 6 months (MD 8.02, 95% CI 4.13 to 11.91; 5 studies, n=499 patients). Pooled analyses also reported a numerical improvement in IDKC for PRP compared to HA at 12 months (MD 5.84, 95% CI -1.05 to 12.71; 3 studies, n=391 patients); however, this was associated with a large amount of uncertainty.
In terms of Lequesne index scores (an assessment of osteoarthritis severity in the knee), pooled analysis reported a numerical improvement in Lequesne index score for PRP compared to HA (MD -1.31, 95% CI -3.50 to 0.89; 3 studies, n=273 patients); however, this was associated with a large amount of uncertainty.
In terms of adverse events, pooled analyses reported no difference in the risk of adverse events for PRP compared to HA (risk ratio [RR] 1.20, 95% CI 0.91 to 1.58; 9 studies, n=637 patients).
The research objective was clearly stated and appropriate inclusion criteria were defined. No restrictions were reported based on study characteristics or sources of information.
|1.1 Did the review adhere to pre-defined objectives and eligibility criteria?||Probably yes|
|1.2 Were the eligibility criteria appropriate for the review question?||Probably yes|
|1.3 Were eligibility criteria unambiguous?||Probably yes|
|1.4 Were all restrictions in eligibility criteria based on study characteristics appropriate (e.g. date, sample size, study quality, outcomes measured)?||Probably yes|
|1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g. publication status or format, language, availability of data)?||Probably yes|
|Concerns regarding specification of study eligibility criteria||Low|
Studies were identifed by searching PubMed (1966-April 2018), EMBASE (1980-April 2018) and the Cochrane Library (1966-April 2018). In addition, the reference lists of included studies were manually searched to identify additional studies. The search strategy was not reported. No restrictions were reported based on date, publication format or language. No information was provided on the number of reviewers involved in the study selection process.
|2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports?||Probably yes|
|2.2 Were methods additional to database searching used to identify relevant reports?||Probably yes|
|2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible?||No information|
|2.4 Were restrictions based on date, publication format, or language appropriate?||Probably yes|
|2.5 Were efforts made to minimise error in selection of studies?||No information|
|Concerns regarding methods used to identify and/or select studies||Unclear|
Two reviewers were independently involved in the data extraction process. Sufficient individual study characteristics were extracted to allow interpretation of results. Relevant study results appear to have been extracted. Methodological quality of the included studies was assessed using the Cochrane Risk of Bias Tool for randomised controlled trials. Two reviewers were independently involved in the risk of bias assessment and any discrepancies were resolved by discussion with a third reviewer.
|3.1 Were efforts made to minimise error in data collection?||Probably yes|
|3.2 Were sufficient study characteristics considered for both review authors and readers to be able to interpret the results?||Probably yes|
|3.3 Were all relevant study results collected for use in the synthesis?||Probably yes|
|3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria?||Yes|
|3.5 Were efforts made to minimise error in risk of bias assessment?||Yes|
|Concerns regarding methods used to collect data and appraise studies||Low|
The synthesis appeared to include all relevant studies. The method of analysis was explained and appeared appropriate. Heterogeneity was assessed and found to be high for some outcomes; the source of this heterogeneity was not formally assessed. Robustness of the findings was not addressed in the synthesis. The quality of individual studies was considered in the synthesis.
|4.1 Did the synthesis include all studies that it should?||Probably yes|
|4.2 Were all pre-defined analyses reported or departures explained?||Probably yes|
|4.3 Was the synthesis appropriate given the degree of similarity in the research questions, study designs and outcomes across included studies?||Probably yes|
|4.4 Was between-study variation minimal or addressed in the synthesis?||Probably no|
|4.5 Were the findings robust, e.g. as demonstrated through funnel plot or sensitivity analyses?||Probably no|
|4.6 Were biases in primary studies minimal or addressed in the synthesis?||Yes|
|Concerns regarding synthesis and findings||High|
PURPOSE: The purpose of this meta-analysis was to compare platelet-rich plasma (PRP) and hyaluronic acid (HA) in patients with knee osteoarthritis (KOA). METHODS: Randomized controlled trials (RCTs) comparing the use of PRP and HA in KOA patients were retrieved from each database from the establishment date to April 2018. Outcome measurements were the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analog scale (VAS), International Knee Documentation Committee, and Lequesne Index scores and adverse events. The pooled data were evaluated with Review Manager 5.3.5. RESULTS: Fifteen RCTs (N = 1,314) were included in our meta-analysis. The present meta-analysis indicated that PRP injections reduced pain more effectively than HA injections in patients with KOA at six and 12 months of follow-up, as evaluated by the WOMAC pain score; the VAS pain score showed a significant difference at 12 months. Moreover, better functional improvement was observed in the PRP group, as demonstrated by the WOMAC function score at three, six, and 12 months. Additionally, PRP injections did not display different adverse event rates compared with HA injections. CONCLUSION: In terms of long-term pain relief and functional improvement, PRP injections might be more effective than HA injections as a treatment for KOA. The optimal dosage, the timing interval and frequency of injections, and the ideal treatment for different stages of KOA remain areas of concern for future investigations.