Meheux, C. J., McCulloch, P. C., Lintner, D. M., Varner, K. E., & Harris, J. D. (2016). Efficacy of Intra-articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Systematic Review. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association, 32(3), 495–505. https://doi.org/10.1016/j.arthro.2015.08.005

Systematic Review

Purpose: To determine (1) whether platelet-rich plasma (PRP) injection significantly improves validated patient-reported outcomes in patients with symptomatic knee osteoarthritis (OA) at 6 and 12 months postinjection, (2) differences in outcomes between PRP and corticosteroid injections or visco supplementation or placebo injections at 6 and 12 months postinjection, and (3) similarities and differences in outcomes based on the PRP formulations used in the analyzed studies.

Methods: PubMed, Cochrane Central Register of Controlled Trials, SCOPUS, and Sport Discus were searched for English-language, level I evidence, human in vivo studies on the treatment of symptomatic knee OA with intra-articular PRP compared with other options, with a minimum of 6 months of follow-up. A quality assessment of all articles was performed using the Modified Coleman Methodology Score (average, 83.3/100), and outcomes were analyzed using 2-proportion z-tests.

Results: Six articles (739 patients, 817 knees, 39% males, mean age of 59.9 years, with 38 weeks average follow-up) were analyzed. All studies met minimal clinical important difference criteria and showed significant improvements in statistical and clinical outcomes, including pain, physical function, and stiffness, with PRP. All but one study showed significant differences in clinical outcomes between PRP and hyaluronic acid (HA) or PRP and placebo in pain and function. Average pretreatment Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were 52.36 and 52.05 for the PRP and HA groups, respectively (P = .420). Mean post-treatment WOMAC scores for PRP were significantly better than for HA at 3 to 6 months (28.5 and 43.4, respectively; P = .0008) and at 6 to 12 months (22.8 and 38.1, respectively; P = .0062). None of the included studies used corticosteroids.

Conclusions: In patients with symptomatic knee OA, PRP injection results in significant clinical improvements up to 12 months postinjection. Clinical outcomes and WOMAC scores are significantly better after PRP versus HA at 3 to 12 months postinjection. There is limited evidence for comparing leukocyte-rich versus leukocyte-poor PRP or PRP versus steroids in this study.

• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used to evaluate the results of the patients. This index is based on patient pain, stiffness, and physical function.
• The efficacy of PRP intra-articular injections was assessed vs hyaluronic acid injections and placebo injections. Corticosteroid injection was not analyzed in this study which is significant as it is a common treatment for knee osteoarthritis.
• 6 studies were evaluated in the systematic review and showed significant improvements in the PRP experimental group up to 12 months post injection.

I chose this article because it was performed in the United States. Many articles examining the efficacy of PRP injections in patients with knee osteoarthritis were foreign articles. It was also directly answering my PICO question. It compared PRP injections to another form of care (Hyaluronic acid) and also placebos which is what my pico question was examining. Examining the patients at a minimum of 6 months allowed for appropriate time to assess the results. Using the WOMAC score, the study was basing results on the same factors that my PICO question was examining (function, pain)

Cole, B. J., Karas, V., Hussey, K., Pilz, K., & Fortier, L. A. (2017). Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis. The American journal of sports medicine, 45(2), 339–346. https://doi.org/10.1177/0363546516665809

Randomized Controlled Trial

Background: The use of platelet-rich plasma (PRP) for the treatment of osteoarthritis (OA) has demonstrated mixed clinical outcomes in randomized controlled trials when compared with hyaluronic acid (HA), an accepted nonsurgical treatment for symptomatic OA. Biological analysis of PRP has demonstrated an anti-inflammatory effect on the intra-articular environment.

Purpose: To compare the clinical and biological effects of an intra-articular injection of PRP with those of an intra-articular injection of HA in patients with mild to moderate knee OA.

Study design: Randomized controlled trial; Level of evidence, 1.

Methods: A total of 111 patients with symptomatic unilateral knee OA received a series of either leukocyte-poor PRP or HA injections under ultrasound guidance. Clinical data were collected before treatment and at 4 time points across a 1-year period. Synovial fluid was also collected for analysis of proinflammatory and anti-inflammatory markers before treatment and at 12 and 24 weeks after treatment. Several measures were used to assess results: (1) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale; (2) International Knee Documentation Committee (IKDC) subjective knee evaluation, visual analog scale (VAS) for pain, and Lysholm knee score; and (3) difference in intra-articular biochemical marker concentrations.

Results: There were 49 patients randomized to treatment with PRP and 50 randomized to treatment with HA. No difference was seen between the groups in the primary outcome measure (WOMAC pain score). In the secondary outcome measure, linear contrasts identified a significantly higher IKDC score in the PRP group compared with the HA group at 24 weeks (mean ± standard error [SE], 65.5 ± 3.6 vs 55.8 ± 3.8, respectively; P = .013) and at final follow-up (52 weeks) (57.6 ± 3.37 vs 46.6 ± 3.76, respectively; P = .003). Linear contrasts also identified a statistically lower VAS score in the PRP group versus the HA group at 24 weeks (mean ± SE, 34.6 ± 3.24 vs 48.6 ± 3.7, respectively; P = .0096) and 52 weeks (44 ± 4.6 vs 57.3 ± 3.8, respectively; P = .0039). An examination of fixed effects showed that patients with mild OA and a lower body mass index had a statistically significant improvement in outcomes. In the biochemical analysis, differences between groups approached significance for interleukin-1β (mean ± SE, 0.14 ± 0.05 pg/mL [PRP] vs 0.34 ± 0.16 pg/mL [HA]; P = .06) and tumor necrosis factor α (0.08 ± 0.01 pg/mL [PRP] vs 0.2 ± 0.18 pg/mL [HA]; P = .068) at 12-week follow-up.

Conclusion: We found no difference between HA and PRP at any time point in the primary outcome measure: the patient-reported WOMAC pain score. Significant improvements were seen in other patient-reported outcome measures, with results favoring PRP over HA. Preceding a significant difference in subjective outcomes favoring PRP, there was a trend toward a decrease in 2 proinflammatory cytokines, which suggest that the anti-inflammatory properties of PRP may contribute to an improvement of symptoms.

•  Improvement was seen in both the HA group and PRP group initially then a decline was seen at the 1 year follow up.
• Results showed that there was significant effects of fixed variables including K-L grade (grade of OA), and BMI. Those with a K-L grade of 1 (mild OA) had a better outcome with both HA and PRP then compared to those with a grade of 3 (more severe OA).
• There was no true significant differences found between the use of HA and PRP. Results did however show that PRP does have anti inflammatory properties.
• The use of both PRP and HA have shown positive outcomes in those with low BMI’s and mild OA.

I chose this article because it was a USA based article, was a randomized controlled trial that directly compared the use of PRP with another common injection used to treat knee osteoarthritis. It was a different type of study then the first article I chose which was a systematic review. When reading this article it also discussed other variables such as BMI and grade of OA which I knew would play an important role in the efficacy of PRP.

Crowley, J. L., & Soti, V. (2023). Platelet-Rich Plasma Therapy: An Effective Approach for Managing Knee Osteoarthritis. Cureus, 15(12), e50774. https://doi.org/10.7759/cureus.50774

Systematic Review and Meta analyses

Platelet-rich plasma (PRP) is a promising non-invasive therapeutic intervention for knee osteoarthritis (KOA) that has generated significant interest due to anecdotal accounts of its efficacy, resulting in reduced recovery time in various orthopedic interventions. This systematic review examines the effectiveness of PRP in managing KOA. Specifically, it seeks to determine the extent to which PRP can treat KOA patients effectively, alleviate KOA symptoms, and improve patient outcomes. Additionally, the review aims to identify the optimal concentration and composition of PRP required to achieve therapeutic results in KOA. Furthermore, the review investigates whether PRP can modify the synovial environment structurally and immunologically to improve outcomes in KOA patients. We conducted a comprehensive literature search on PubMed, Orthogate, Clinicaltrials.gov, and Embase of clinical trials investigating PRP treatment in KOA patients in the last five years. The results indicated that PRP is effective in treating KOA patients. Evidence shows that PRP therapy can alleviate pain, enhance joint function, increase range of motion, and improve mobility in KOA patients. PRP was effective in treating KOA when the mean platelet concentration of PRP treatment was 4.83 to 5.91 times higher than the baseline whole blood platelet concentration. However, studies investigating PRP with a mean platelet concentration of 3.48 to 4.04 times higher than baseline failed to demonstrate statistically significant improvements. PRP therapy slowed down KOA progression, which validates its effectiveness in impeding further structural damage and arresting the degenerative impact of the disease. Nonetheless, further investigation is necessary to examine how PRP therapy can modify the progression of the disease. Furthermore, future research should identify the most effective platelet concentration levels that provide optimal symptom relief. There is a need for further research to identify the specific PRP configuration that is most pertinent in a clinical setting, as there is a lack of standardization in PRP manufacturing protocols, including the variety of experimental setups and dosing schedules utilized in different studies.

• Systematic review that assess the efficacy of PRP injections. Outcomes were evaluated based on alleviating patients pain, enhancing function, increasing mobility and range of motion.
• The study also looked at the platelet concentration of the PRP injections in evaluating outcomes.
• Early evidence shows that there can be benefits of PRP when used at the right concentration, but the systematic review states that further investigation is needed to evaluate optimal concentration, and there is need for standardization of PRP manufacturing protocols before it could be ensured to be effective.

I chose this article because it was based in the United States and it discussed a different variable (concentration) that the other articles did not delve deeply into. It also discussed the failure of standardization protocols in regard to marketing PRP. This was something I found interesting and plan to research further into. When discussing the efficacy of a drug, safety is most important, and standardization is required if it could effectively help patients suffering from knee OA.   Though this wasn’t directly related to my PICO question the article did answer it and delved deeper into those other aspects mentioned above.