Comparative efficacy of platelet-rich plasma, corticosteroid, hyaluronic acid, and placebo

Key points

1. 01No injection outperformed saline placebo for pain or function at 12 weeks or beyond
2. 02Corticosteroid gave the fastest early pain relief (weeks 1-4) but this benefit faded and recovery at 52 weeks was worst in that group
3. 03At one year, 40 of 54 available patients had complete absence of pain regardless of which injection they received
4. 04The mechanical peppering technique used identically in all groups may explain much of the improvement, independent of the injected substance
5. 05All injections were well tolerated; no serious adverse events occurred in any group

How it was conducted

Design

Single-center, double-blind, prospective randomized controlled trial (CONSORT-reported; ClinicalTrials.gov NCT04521387)

Participants

60 adults aged 31-60 with lateral elbow tendinopathy for at least 3 months, unresponsive to rehabilitation, no prior injections

Groups

PRP n=30, corticosteroid (betamethasone 7 mg/mL) n=10, hyaluronic acid (40 mg) n=10, saline placebo n=10; all via ultrasound-guided peppering technique

Primary outcomes

VAS pain (average, at rest, during provocative tests) and PRTEE questionnaire score

Follow-up

1, 4, 12, 24, and 52 weeks post-injection

Success criterion

Minimal clinically important difference (MCID): 1.5 points VAS, 11 points PRTEE

What they found

• MCID for VAS pain reduction achieved in 25 patients at 1 week, 35 at 4 weeks, 43 at 12 weeks, 50 at 24 weeks, and 52 of 54 available patients at 52 weeks (all groups combined)
• MCID for PRTEE improvement achieved in 30 patients at 4 weeks, 40 at 12 weeks, 53 at 24 weeks, and 54 at 52 weeks (all groups combined)
• Complete absence of pain (VAS=0) in 2 patients at 1 week (both CS group), 5 at 4 weeks, 10 at 12 weeks, 22 at 24 weeks, and 40 at 52 weeks (all groups combined)
• At 1 week, CS group mean VAS 2.15 +/- 2.0 vs PRP 4.25 +/- 1.92, HA 4.9 +/- 2.6, PL 4.9 +/- 2.23 (p<0.05 before Bonferroni correction, non-significant after)
• At 4 weeks, Thomson's test VAS: PRP 6 +/- 2.51 vs CS 3.15 +/- 2.54 (p<0.05 before Bonferroni correction, non-significant after)
• No statistically significant between-group differences in VAS, PRTEE, PPT, DASH, SEV, grip strength, or key-pinch strength at any follow-up after Bonferroni correction
• All groups combined showed significant VAS improvement from baseline (5.64 +/- 1.76) to 4 weeks (3.41 +/- 2.02), 12 weeks (2.81 +/- 2.19), 24 weeks (1.54 +/- 1.91), and 52 weeks (0.6 +/- 1.37), all p<0.01
• At 52 weeks, complete pain resolution in approximately 74% of all available patients; lowest complete recovery rate was in the CS group (approximately 50%)

Limitations

• Study was underpowered: only 60 of 120 planned participants enrolled due to COVID-19 restrictions, resulting in unequal group sizes (PRP n=30 vs 10 per other group) and insufficient power to detect moderate between-group differences
• No non-injection control arm (physiotherapy or wait-and-see), so the contribution of the mechanical peppering technique versus the injected substance cannot be separated
• Unblinded allocation deviation due to quasi-parallel enrollment creates risk of selection bias in the CS, HA, and placebo groups
• Short follow-up on between-group comparisons and small sub-groups limit generalizability, particularly for HA and placebo conclusions

Why it matters

For patients

People with tennis elbow that has not improved with exercise can expect similar long-term improvement from any of these injections, including a simple saline injection, though corticosteroid may ease pain faster in the first few weeks.

For clinicians

No injection therapy demonstrated superiority over placebo at 12 weeks or beyond; the identical peppering technique used across all groups may be the active ingredient, supporting a re-evaluation of costly biologics like PRP for this indication.

For readers

This RCT directly challenges the premise that PRP or hyaluronic acid outperform placebo for tennis elbow, reinforcing findings from recent meta-analyses and suggesting the needle technique itself may drive outcomes.