Background
Lateral elbow pain, also known as tennis elbow or lateral epicondylitis, is a degenerative (age-related structural change of tissue) tendon disease at the site where forearm extensor muscles attach to the outer part of the elbow. It is a common cause of elbow pain and disability, typically in middle-aged people.
Autologous blood and platelet-rich plasma (PRP) injections have been suggested to improve tendon healing. Autologous blood is derived from the person's own venous blood sample (blood taken from a vein), and PRP is a concentrate of plasma and platelets isolated from autologous blood.
This study aimed to review evidence regarding the benefits and harms of autologous blood or PRP injection for treatment of lateral elbow pain.
Study characteristics
We searched MEDLINE, CENTRAL, Embase, Clinicaltrials.gov, and WHO trials registries, unrestricted by date or language, on 18 September 2020.
We included 32 trials with 2337 participants. Mean age varied between 36 years and 53 years, and mean duration of symptoms ranged from 1 month to 22 months. Of 21 studies that reported gender, 56% of participants were female. Among the included studies, three studies were funded by manufacturers of the PRP centrifugation system; two studies were provided PRP kits; and one study received funding from PRP kit manufacturers.
Key findings
Comparison with placebo at three months revealed the following.
Pain (lower scores mean less pain) (8 studies, 523 participants; moderate-certainty evidence).
Pain improved by 2% (3% worse to 6% better), or by 0.16 points on a zero to 10 scale.
• People who had placebo rated their pain as 3.7 points.
• People who had autologous blood or PRP injection rated their pain as 3.9 points.
Function (0 to 100; lower scores mean better function or less disability) (8 studies, 502 participants; moderate-certainty evidence).
Function improved by 2% (5% better to 1% worse), or by 2 points on a zero to 100 scale.
• People who had placebo rated their function as 27 points.
• People who had autologous blood or PRP injection rated their function as 29 points.
Treatment success (4 studies, 372 participants; very low-certainty evidence).
0% more people rated their treatment a success (11% fewer to 12% more), or zero more people out of 100.
• 65 out of 100 people considered treatment as successful after placebo injection.
• 67 out of 100 people considered treatment as successful after autologous blood or PRP injection.
Health-related quality of life (higher scores mean better quality of life).
None of the studies measured this outcome.
Pain relief (> 30% or > 50%).
None of the studies reported this outcome at three months.
Withdrawals due to adverse events (1 study, 80 participants; very low-certainty evidence).
5% fewer people withdrew from the study because of an adverse event (7.5% fewer to 14.8% more), or 5 fewer people out of 100.
• 7 out of 100 people withdrew from the study due to an adverse event after placebo injection.
• 2 out of 100 people withdrew from the study due to an adverse event after autologous blood or PRP injection.
Adverse events (typically transient injection site pain) (5 studies, 425 participants; low-certainty evidence).
2% more people had adverse events (4% fewer to 11% more), or 2 more people out of 100.
• 17 out of 100 people reported adverse events after placebo injection.
• 19 out of 100 people reported adverse events after autologous blood or PRP injection.
Certainty of the evidence
For people with lateral elbow pain, moderate-certainty evidence (downgraded for bias, i.e. methodological shortcomings in the included studies) shows that autologous blood or PRP injection probably provides little or no clinically important benefit for pain or function compared with placebo injection, and low-certainty evidence (downgraded due to risk of bias, i.e. methodological shortcomings; and imprecision, i.e. too few data to estimate the precise difference) suggests that autologous blood or PRP injection may not cause higher risk for adverse events. We are uncertain whether autologous blood or PRP injection is associated with a higher proportion of people reporting treatment success, or if this treatment increases withdrawals due to adverse events.
Data in this review do not support the use of autologous blood or PRP injection for treatment of lateral elbow pain. These injections probably provide little or no clinically important benefit for pain or function (moderate-certainty evidence), and it is uncertain (very low-certainty evidence) whether they improve treatment success and pain relief > 50%, or increase withdrawal due to adverse events. Although risk for harm may not be increased compared with placebo injection (low-certainty evidence), injection therapies cause pain and carry a small risk of infection. With no evidence of benefit, the costs and risks are not justified.
Autologous whole blood or platelet-rich plasma (PRP) injections are commonly used to treat lateral elbow pain (also known as tennis elbow or lateral epicondylitis or epicondylalgia). Based on animal models and observational studies, these injections may modulate tendon injury healing, but randomised controlled trials have reported inconsistent results regarding benefit for people with lateral elbow pain.
To review current evidence on the benefit and safety of autologous whole blood or platelet-rich plasma (PRP) injection for treatment of people with lateral elbow pain.
We searched CENTRAL, MEDLINE, and Embase for published trials, and Clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal for ongoing trials, on 18 September 2020.
We included all randomised controlled trials (RCTs) and quasi-RCTs comparing autologous whole blood or PRP injection therapy to another therapy (placebo or active treatment, including non-pharmacological therapies, and comparison between PRP and autologous blood) for lateral elbow pain. The primary comparison was PRP versus placebo. Major outcomes were pain relief (≥ 30% or ≥ 50%), mean pain, mean function, treatment success, quality of life, withdrawal due to adverse events, and adverse events; the primary time point was three months.
We used standard methodological procedures expected by Cochrane.
We included 32 studies with 2337 participants; 56% of participants were female, mean age varied between 36 and 53 years, and mean duration of symptoms ranged from 1 to 22 months. Seven trials had three intervention arms. Ten trials compared autologous blood or PRP injection to placebo injection (primary comparison). Fifteen trials compared autologous blood or PRP injection to glucocorticoid injection. Four studies compared autologous blood to PRP. Two trials compared autologous blood or PRP injection plus tennis elbow strap and exercise versus tennis elbow strap and exercise alone. Two trials compared PRP injection to surgery, and one trial compared PRP injection and dry needling to dry needling alone. Other comparisons include autologous blood versus extracorporeal shock wave therapy; PRP versus arthroscopic surgery; PRP versus laser; and autologous blood versus polidocanol.
Most studies were at risk of selection, performance, and detection biases, mainly due to inadequate allocation concealment and lack of participant blinding.
We found moderate-certainty evidence (downgraded for bias) to show that autologous blood or PRP injection probably does not provide clinically significant improvement in pain or function compared with placebo injection at three months. Further, low-certainty evidence (downgraded for bias and imprecision) suggests that PRP may not increase risk for adverse events. We are uncertain whether autologous blood or PRP injection improves treatment success (downgraded for bias, imprecision, and indirectness) or withdrawals due to adverse events (downgraded for bias and twice for imprecision). No studies measured health-related quality of life, and no studies reported pain relief (> 30% or 50%) at three months.
At three months, mean pain was 3.7 points (0 to 10; 0 is best) with placebo and 0.16 points better (95% confidence interval (CI) 0.60 better to 0.29 worse; 8 studies, 523 participants) with autologous blood or PRP injection, for absolute improvement of 1.6% better (6% better to 3% worse). At three months, mean function was 27.5 points (0 to 100; 0 is best) with placebo and 1.86 points better (95% CI 4.9 better to 1.25 worse; 8 studies, 502 participants) with autologous blood or PRP injection, for absolute benefit of 1.9% (5% better to 1% worse), and treatment success was 121 out of 185 (65%) with placebo versus 125 out of 187 (67%) with autologous blood or PRP injection (risk ratio (RR) 1.00; 95% CI 0.83 to 1.19; 4 studies, 372 participants), for absolute improvement of 0% (11.1% lower to 12.4% higher).
Regarding harm, we found very low-certainty evidence to suggest that we are uncertain whether withdrawal rates due to adverse events differed. Low-certainty evidence suggests that autologous blood or PRP injection may not increase adverse events compared with placebo injection. Withdrawal due to adverse events occurred in 3 out of 39 (8%) participants treated with placebo versus 1 out of 41 (2%) treated with autologous blood or PRP injection (RR 0.32, 95% CI 0.03 to 2.92; 1 study), for an absolute difference of 5.2% fewer (7.5% fewer to 14.8% more). Adverse event rates were 35 out of 208 (17%) with placebo versus 41 out of 217 (19%) with autologous blood or PRP injection (RR 1.14, 95% CI 0.76 to 1.72; 5 studies; 425 participants), for an absolute difference of 2.4% more (4% fewer to 12% more).
At six and twelve months, no clinically important benefit for mean pain or function was observed with autologous blood or PRP injection compared with placebo injection.