CAT
RT7-WK2 PICO Expanded to CAT
Clinical Scenario:
58 y/o male with osteoarthritis presents to primary care physician with concerns over knee pain. The patient is interested in treatment for knee osteoarthritis that does not involve surgery and asks about intraarticular injections. The patient mentions that he has heard of hyaluronic acid and platelet-rich plasma as options for intraarticular injections and is curious about the efficacy and safety of each.
PICO Question:
In adults with knee osteoarthritis, do intraarticular injections of platelet-rich plasma or hyaluronic acid have greater efficacy and safety?
Question Type:
☐Prevalence ☐Screening ☐Diagnosis
☐Prognosis ☒Treatment ☐Harms
Assuming that the highest level of evidence to answer your question will be meta-analysis or systematic review, what other types of study might you include if these are not available (or if there is a much more current study of another type)? Please explain your choices.
– If meta-analysis or systematic review are not available, randomized controlled clinical trials will also offer great supporting evidence as they are carefully planned experiments, reduce the potential for bias, and allow for comparison between intervention and control groups.
– Cohort studies could also be used since they allow to follow the patients who have already received a particular treatment forward over time. This is not as reliable as randomized controlled clinical trials since patients might differ in ways other than in the variable that is being observed.
Search terms:
| P | I | C | O |
| Adults | Platelet-rich plasma | Hyaluronic acid | Efficacy |
| Osteoarthritis | PRP | HA | Safety |
| Knee | Clinical Outcomes | ||
| WOMAC Osteoarthritis score | |||
| IKDC score |
Results found:
PubMed:
- Adult, knee osteoarthritis, intraarticular injection, hyaluronic acid, platelet-rich plasma (56)
- Adult, knee osteoarthritis, intraarticular injection, hyaluronic acid, platelet-rich plasma, 10 years, systematic review, meta-analysis (16)
Google Scholar:
- Adult, knee osteoarthritis, intraarticular injection, hyaluronic acid, platelet-rich plasma (1)
Medline Complete:
- Adult, knee osteoarthritis, intraarticular injection, hyaluronic acid, platelet-rich plasma (230)
- Adult, knee osteoarthritis, intraarticular injection, hyaluronic acid, platelet-rich plasma, 10 years, systematic review, meta-analysis (83)
Cochrane Library:
- Adult, knee osteoarthritis, intraarticular injection, hyaluronic acid, platelet-rich plasma (106)
- Adult, knee osteoarthritis, intraarticular injection, hyaluronic acid, platelet-rich plasma, 10 years, systematic review, meta-analysis (3)
A lot of research on this topic was done within the last decade and includes many different types of studies. I was able to find many articles and among them many meta-analyses and systematic reviews from the last few years. I narrowed down search results by limiting research to 10 years and only systematic reviews and meta-analyses. I was able to gather great articles with these limits and they each addressed my question perfectly. Most of my articles were from PubMed and Medline, as Google Scholar yielded only one result, and Cochrane library did not produce many articles either.
Articles chosen for inclusion:
| Citation:
Belk JW, Kraeutler MJ, Houck DA, Goodrich JA, Dragoo JL, McCarty EC. Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Am J Sports Med. 2021 Jan;49(1):249-260. doi: 10.1177/0363546520909397. Epub 2020 Apr 17. PMID: 32302218. |
| Type of article: Systematic review and meta-analysis |
| Abstract: Background: Platelet-rich plasma (PRP) and hyaluronic acid (HA) are 2 nonoperative treatment options for knee osteoarthritis (OA) that are supposed to provide symptomatic relief and help delay surgical intervention. Purpose: To systematically review the literature to compare the efficacy and safety of PRP and HA injections for the treatment of knee OA. Study Design: Meta-analysis of level 1 studies. Methods: A systematic review was performed by searching PubMed, the Cochrane Library, and Embase to identify level 1 studies that compared the clinical efficacy of PRP and HA injections for knee OA. The search phrase used was platelet-rich plasma hyaluronic acid knee osteoarthritis randomized. Patients were assessed via the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain, and Subjective International Knee Documentation Committee (IKDC) scale. A sub-analysis was also performed to isolate results from patients who received leukocyte-poor and leukocyte-rich PRP. Results: A total of 18 studies (all level 1) met inclusion criteria, including 811 patients undergoing intra-articular injection with PRP (mean age, 57.6 years) and 797 patients with HA (mean age, 59.3 years). The mean follow-up was 11.1 months for both groups. Mean improvement was significantly higher in the PRP group (44.7%) than the HA group (12.6%) for WOMAC total scores (P \ .01). Of 11 studies based on the VAS, 6 reported PRP patients to have significantly less pain at latest follow-up when compared with HA patients (P \ .05). Of 6 studies based on the Subjective IKDC outcome score, 3 reported PRP patients to have significantly better scores at latest follow-up when compared with HA patients (P \ .05). Finally, leukocyte-poor PRP was associated with significantly better Subjective IKDC scores versus leukocyte-rich PRP (P \ .05). Conclusion: Patients undergoing treatment for knee OA with PRP can be expected to experience improved clinical outcomes when compared with HA. Additionally, leukocyte-poor PRP may be a superior line of treatment for knee OA over leukocyte- rich PRP, although further studies are needed that directly compare leukocyte content in PRP injections for treatment of knee OA. |
| belk |
| Citation:
Gong H, Li K, Xie R, Du G, Li L, Wang S, Yin J, Gu J, Wang P, Chen M, Hou X. Clinical therapy of platelet-rich plasma vs hyaluronic acid injections in patients with knee osteoarthritis: A systematic review and meta-analysis of randomized double-blind controlled trials. Medicine (Baltimore). 2021 Mar 26;100(12):e25168. doi: 10.1097/MD.0000000000025168. PMID: 33761693. |
| Type of article:
Systematic review and meta-analysis |
| Abstract: Objective: Knee osteoarthritis (KOA) is the most common degenerative disease of the joints caused by articular cartilage injury, degeneration of joint edges and hyperplasia of subchondral bone. The purpose of this study is to investigate the efficacy and safety of clinical therapy of platelet-rich plasma vs hyaluronic acid injections in patients with KOA. Methods: We systematically investigated Pubmed, Embase, and the Cochrane Library for all related articles published through May 2020. Any study was included that compared the effect of platelet-rich plasma (PRP) and hyaluronic acid (HA) in patients with KOA. The search terms included “platelet-rich plasma,” “PRP,” “hyaluronic acid,” “HA,” “knee,” “osteoarthritis,” “arthritis,” “KOA”. Review Manager 5.3 was used to analyze and calculate data regarding these outcome indicators. Results: In this study, six randomized double-blind controlled trials were included, including 338 patients in the PRP group and 323 patients in the HA group. Meta-analysis results showed that the Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) Total Score was differed significantly between the PRP and HA groups at the 1, 6, 12months follow-up (MD=3.39, 95% CI: 2.85–3.92, P < .05). In a comparison of Physical function scores at the 12 months follow-up, PRP improved knee function scores more than HA (MD = 3.28; 95% CI: 2.13–4.43; P<.05). However, International Knee Documentation Committee (IKDC), Tegner Activity scores, EuroQol visual analogue scale (EQ-VAS), and Adverse Events (AEs) were all not significantly different (P>.05). Results showed that compared with HA, PRP had significant advantages in relevant improving knee function and quality of life. |
| gong |
| Citation:
Tang JZ, Nie MJ, Zhao JZ, Zhang GC, Zhang Q, Wang B. Platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: a meta-analysis. J Orthop Surg Res. 2020 Sep 11;15(1):403. doi: 10.1186/s13018-020-01919-9. PMID: 32912243; PMCID: PMC7488405. |
| Type of article:
Meta-analysis |
| Abstract:.
Background: This study aimed to evaluate the clinical efficacy of platelet-rich plasma (PRP) injection compared with hyaluronic acid (HA) injection for patients undergoing knee osteoarthritis. Methods: We systematically searched electronic databases including PubMed, Embase, Web of Science, and the Cochrane Library on January 23, 2020 to identify relevant studies issued in English languages. The outcomes evaluating the efficacy of knee osteoarthritis (KOA) treatment were Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores (WOMAC pain, function, stiffness, and total scores) at 1, 3, 6, and 12 months; International Knee Documentation Committee (IKDC) scores, Lequesne Index score, Visual Analog Scale (VAS) scores, EQ-VAS scores, and KOOS scores. The pooled data were analyzed by Stata 12.0. Results: A total of 20 RCTs were enrolled in the present meta-analysis. The pooled results demonstrated that platelet-rich plasma (PRP) injection reduced pain more effectively than hyaluronic acid (HA) injection at 6-month and 12-month follow-up evaluated by WOMAC pain scores and VAS scores. EQ-VAS in the patients treated with PRP injection was lower than that in patients with HA injection at 12 months. Moreover, the patients with PRP injection had a better function recovery than those with HA injection at 1-month, 3-month, 6-month, and 12-month follow- up, as evaluated by WOMAC function scores. WOMAC total scores showed significant difference at 6-month and 12-month follow-up. The IKDC scores indicated PRP injection was significantly more effective than HA injection at 3 months and 6 months. However, the Lequesne Index scores, KOOS scores, and adverse events did not show any significant difference between groups. Conclusion: Intra-articular PRP injection appeared to be more efficacious than HA injection for the treatment of KOA in terms of short-term functional recovery. Moreover, PRP injection was superior to HA injection in terms of long-term pain relief and function improvement. In addition, PRP injection did not increase the risk of adverse events compared to HA injection. |
| Tang |
| Citation:
Tan J, Chen H, Zhao L, Huang W. Platelet-Rich Plasma Versus Hyaluronic Acid in the Treatment of Knee Osteoarthritis: A Meta-analysis of 26 Randomized Controlled Trials. Arthroscopy. 2021 Jan;37(1):309-325. doi: 10.1016/j.arthro.2020.07.011. Epub 2020 Jul 15. PMID: 32679294. |
| Type of article:
Meta-analysis |
| Abstract: Purpose: To compare the effectiveness and safety of platelet-rich plasma (PRP) and hyaluronic acid (HA) in patients with adult knee osteoarthritis (KOA) and to explore the most effective and safe protocol by using a meta-analysis method. Methods: This study was based on Cochrane methodology for conducting a meta-analysis. Only randomized controlled trials with an experimental group that used PRP and a control group that received HA were eligible for this study. The participants were adults who had KOA. The outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the visual analog scale (VAS), the EuroQol VAS, the International Knee Documentation Committee, the Tegner score, the Lequesne Scale, the Knee injury Osteoarthritis Outcome Score, satisfaction rate, and adverse events. Subgroup analyses was performed for patients with different doses, types, and times of PRP interventions and grades of OA. The Review Manager Database was used to analyze the included studies. Results: Twenty-six randomized controlled trials involving 2430 patients were included. The WOMAC total scores, WOMAC physical function scores, and VAS scores of the PRP group were better than the those of the HA group at 3, 6, and 12 months. The PRP group had better WOMAC pain, WOMAC stiffness, EuroQol VAS, and International Knee Documentation Committee scores than the HA group at 6 and 12 months. There was no significant difference in adverse events between the 2 groups (relative risk 1.21, 95% confidence interval 0.95-1.54; P 1⁄4 .13). Conclusions: For the nonsurgical treatment of KOA, compared with HA, intra-articular injection of PRP could significantly reduce patients’ early pain and improve function. There was no significant difference in adverse events between the 2 groups. PRP was more effective than HA in the treatment of KOA, and the safety of these 2 treatment options was comparable. |
| tan2020 |
| Citation:
Mojica ES, Markus DH, Hurley ET, Blaeser AM, Jazrawi LM, Campbell KA, Strauss EJ. Estimated Time to Maximum Medical Improvement of Intra-articular Injections in the Treatment of Knee Osteoarthritis-A Systematic Review. Arthroscopy. 2021 Aug 27:S0749-8063(21)00777-5. doi: 10.1016/j.arthro.2021.08.026. Epub ahead of print. PMID: 34461219. |
| Type of article:
Systematic review |
| Abstract:
Purpose: The purpose of the current study is to perform a systematic review of the literature and evaluate maximum medical improvement and minimal clinically important difference (MCID) of different injectables in the treatment of symptomatic knee osteoarthritis. Methods: A systematic review was performed to evaluate maximum medical improvement and MCID in patients undergoing injections of different modalities for knee osteoarthritis. Demographic factors of the patients being reviewed were analyzed, with patient-reported outcomes as reported by visual analog scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) being used to evaluate the clinical trajectory of patients receiving intra-articular injections. Results: Overall, 79 (level of evidence I: 79) studies met inclusion criteria, with 8761 patients. Corticosteroid (CS) injections, middle molecular weight hyaluronic acid (MMW-HA), and leukocyte-rich platelet rich plasma (LR-PRP) injections reached their maximum pain control at 4 to 6 weeks after injection, as measured by VAS. The lowest VAS scores were reached for low molecular weight hyaluronic acid (LMW-HA), high molecular weight hyaluronic acid (HMW-HA), and leukocyte-poor platelet rich plasma (LP-PRP) by 3 months after injection. Similarly, the WOMAC scores were lowest at 4 to 6 weeks after CS and MMW-HA injections, and at 3 months after HMW-HA and LP-PRP injections. LR-PRP demonstrated the most prolonged pain relief relative to the other injection types, with the lowest VAS score of all groups measured at final follow-up. LP-PRP showed the lowest WOMAC scores at final follow-up, one year post-injection. Conclusion: PRP injections provide continued pain relief at up to 1 year after injection. Corticosteroids and hyaluronic acid have good efficacy and are suitable for many patients but lack this longevity. |
| Mojica |
| Citation:
Raeissadat, Seyed Ahmad et al. “The comparison effects of intra-articular injection of Platelet Rich Plasma (PRP), Plasma Rich in Growth Factor (PRGF), Hyaluronic Acid (HA), and ozone in knee osteoarthritis; a one year randomized clinical trial.” BMC musculoskeletal disorders vol. 22,1 134. 3 Feb. 2021, doi:10.1186/s12891-021-04017-x |
| Type of article:
Randomized Clinical Trial |
| Abstract:
Background Our study compares the short and long-term efficacy of the intra articular injections (IAIs) of hyaluronic acid (HA), platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), and ozone in patients with knee osteoarthritis (OA). Methods Results Conclusions |
| raeissadat |
Summary of the evidence:
| Author and Date | Level of Evidence | Sample/Setting
(# of subjects/studies, cohort, etc.) |
Outcomes Studied | Key Findings | Limitations and Biases |
| Belk, et al.
2020 |
Systematic Review and Meta-analysis | 18 studies included with 1608 patients. 811 patients in the Platelet-rich plasma (PRP) group and 797 patients in the hyaluronic acid (HA) group. Mean patient age was 57.6 in PRP group and 59.3 in HA group. Mean follow-up time was 11.1 months for each group. Males made up 40.9% of PRP group and 40.6% of HA group. | Patient-reported outcomes including the Visual Analog Scale for pain, WOMAC score, and IKDC score. | WOMAC scores were significantly improved in the PRP groups in more studies than in the HA groups.
Pooled analysis showed that at 12 months, PRP resulted in significantly better WOMAC scores than HA.
PRP patients reported significantly better VAS scores than HA patients.
At 12 months, IKDC scores were significantly improved in PRP group over HA group. |
No studies reported how many patients ultimately required arthroplasty.
PRP and HA administration techniques were not identical across all studies. |
| Gong, et al.
2021 |
Systematic review and meta-analysis | 6 double-blind randomized clinical studies including a total of 661 patients with 338 in the PRP group and 323 in the HA group. Patient age ranged between 45 and 65. Follow-up period was 6 to 24 months. | Primary outcomes included the WOMAC score and secondary outcomes included the IKDC score, EQ-VAS score, Tegner activity scores, and adverse effects. | WOMAC scores of PRP group were significantly different from HA group, with PRP patients reporting more improvement.
No significant difference found in IKDC scores between PRP and HA.
No significant difference found in EQ-VAS scores between PRP and HA.
No significant difference in recovery assessed by Tegner activity score between PRP and HA groups.
No significant difference in adverse effects between PRP and HA groups. |
Small number of included trials.
Sample size of each study was insufficient which could potentially increase heterogeneity. |
| Tang, et al.
2020 |
Meta-analysis | A total of 1281 patients were studied with 654 in the PRP group and 627 in HA group. Follow-up period ranged from 3 to 18 months. Groups had similar demographic features. | WOMAC scores, including total, function, stiffness, and pain categories, as well as VAS score, IKDC score, Lequesne Index score, EQ-VAS score, KOOS, and adverse events. | WOMAC score improved in PRP group at 1 month and 12 months, with no difference seen at 3 months.
VAS scores showed improvement in pain in PRP group at all time intervals.
PRP was found to be more effective than HA in terms of the IKDC scores at all intervals except two months.
PRP was more effective than HA in regards to Lequesne index scores.
No significant difference between PRP and HA regarding the EQ-VAS score.
Improved KOOS scores seen in PRP group.
No significant difference in adverse events between the two groups. |
Most of the analyses had heterogeneity.
PRP injection administration varied between studies. |
| Tan, et al.
2020 |
Meta-analysis | 26 randomized-control trials included with 2430 patients. | WOMAC scores, EQ-VAS score, IKDC score, Tegner score, Lequesne scale, KOOS score, American Knee Society score, reintervention rate, satisfaction rate, adverse events. | No significant difference in adverse events between PRP and HA groups, with mild pain and swelling most commonly reported.
In regard to WOMAC score, no significant difference between PRP and HA seen at 1 month, and PRP group showing improved scores at 3 months, 6 months, and 12 months.
Less pain reported in PRP group in terms of VAS score at 1, 3, 6 and 12 months.
IKDC scores were better in PRP group at 6 and 12 months.
Tegner scores were improved in PRP group at 12 months but no difference seen at 2 and 6 months.
No significant difference between PRP and HA in terms of Lequesne scale and KOOS score. |
Significant heterogeneity in WOMAC scores, EQ-VAS scores, and IKDC scores.
No sufficient data to analyze American Knee Society score and reintervention rate. |
| Mojica, et al.
2021 |
Systematic review | 79 randomized control trials included with a total of 8,761 patients. Mean follow-up was 7.3 months. Study compared different types of HA and PRP, including leukocyte poor (LP-PRP) and leukocyte rich (LR-PRP) platelet-rich plasma and hyaluronic acid of low, medium, and high molecular weight. Other treatments were also evaluated in this study. | Outcomes studies included VAS scores and WOMAC scores. | Lowest VAS score was found in group receiving LP-PRP 3 months post injection.
Best outcomes in terms of WOMAC scores were seen with LR-PRP, which was also found to show improvement after one year of follow-up. |
Included studies demonstrated some potential risk of bias mostly due to inappropriate binding. |
| Raeissadat, et al.
2021 |
Randomized clinical trial | 200 patients with mild to moderate knee osteoarthritis were included in this randomized clinical trial and separated into four groups of treatments, including HA, PRP, plasma rich in growth factors, and ozone. | Outcomes of pain relief and functional improvement were assessed with the Visual Analog Scale, WOMAC score, and the Lequesne index. | At 6 month follow-up, PRP showed better improvement with VAS and WOMAC scores than HA.
At 12 months, PRP had statistically significant improvement over HA.
PRP was found to be more effective at pain relief and improving function than HA. |
Study was conducted outside of the United states, so the patient population may not be comparable to the U.S. and lacked a placebo group. |
Conclusions:
Article 1 (Belk): The results of this systematic review suggest that patients undergoing intraarticular injections with platelet-rich plasma can expect significantly improved clinical outcomes at short-term follow-up as well as after 12 months as compared to hyaluronic acid. Platelet-rich plasma showed significant improvements over hyaluronic acid in various scores used for subjective assessment of osteoarthritis, including the WOMAC, IKDC, and VAS scores.
Article 2 (Gong): Compared to hyaluronic acid, platelet-rich plasma injections can improve WOMAC scores in patients. No difference was found in IKDC and EQ-VAS scores between the two groups and rate of adverse effects was similar.
Article 3 (Tang): Intraarticular PRP injection appeared to have superior efficacy over HA in terms of short-term and long-term recovery as well as pain relief and function improvement. PRP did not increase the risk of adverse events.
Article 4 (Tan): When compared to hyaluronic acid, platelet-rich plasma could significantly reduce patients pain and improve function non-surgical treatment of knee osteoarthritis. No significant difference in adverse effects was found between the two injections. Safety of the two treatments was comparable.
Article 5 (Mojica): PRP injections provide continued pain relief at one-year post-injection. Hyaluronic acid is effective but lacks the longevity of PRP.
Article 6 (Raeissadat): Injections of PRP can significantly improve symptoms of knee osteoarthritis long-term over hyaluronic acid.
Overall Conclusion: The overarching conclusion of the results of these studies is that intraarticular injection with platelet-rich plasma is more effective than hyaluronic acid in reducing pain and improving function in patients with knee osteoarthritis. The effects are seen both at short-term intervals such as 3 months post-injection, as well as at longer time intervals like 12 months post-injection. The studies also found PRP and HA to have similar rates of adverse events, meaning one is not any safer than the other and both have low adverse effects overall.
Clinical Bottom Line:
Treatment of osteoarthritis is important as patients quality of life diminishes when their knee pain and function declines. Nonsurgical treatment is optimal for many patients either due to underlying health conditions that would not be optimal for surgery or personal choice of wanting to avoid surgery and try more conservative management. While pain medication can curb symptoms for some time, it is not an optimal treatment due to medication side effects and progression of disease. Intraarticular injections are a great option for many patients as they can be administered infrequently and provide pain relief and improved function for months at a time. Hyaluronic acid has been at the center of treatment with intraarticular injections for a long time, but platelet-rich plasma has come forth as another option. While the general consensus is that hyaluronic acid injections are effective and safe, platelet-rich plasma appears to provide better pain relief and improvement in function while having similar rates of adverse effects. The majority of the above studies found significant improvement and higher effectiveness of PRP as compared to HA, with effects seen both short term and long term while having similar adverse effects. Treating patients with platelet-rich plasma injections instead of hyaluronic acid could provide more sustained pain relief and decrease the amount of injections needed for symptom control of knee osteoarthritis.
Weight of Evidence:
I weighed the study by Belk, et al. (article 1) as first. This study is of a high level of evidence, being a systematic review and meta-analysis of 1608 patients. The patient characteristics were very reflective of the most common osteoarthritis patient population and the study assessed many patient-reported outcomes as well as safety. The study was well-designed and had few limitations and biases, making the results trustworthy and reliable.
I weighed the study by Tan, et al. (article 4) as second because it’s a very recent meta-analysis with 2430 patients. The large patient sample size makes the results more reliable, and the study utilized the largest amount of different scores and scales to assess pain, function, and patient satisfaction. Though there was some heterogeneity found, the study was well-built and provided a vast amount of information about PRP and HA in regards to many different outcomes.
I weighed the study by Tang, et al. (article 3) as third because it’s a meta-analysis from 2020, making it a high level of evidence that’s recently published. The study had a large sample size of 1281 patients and a long follow-up of 18 months. While all of this makes for a solid set of data to base clinical decisions on, the study reported heterogeneity in most of its results, making it less reliable than the previous two studies.
I weighed the study by Gong, et al. (article 2) as fourth due to it being a systematic review and meta-analysis published in 2021. The study analyzed 6 double-blind randomized clinical studies but only included a total of 661 patients. Being a recently published high level of evidence study makes me weigh this higher than the remaining articles, but not weigh this evidence too much as the sample size was on the lower side.
I weighed the study by Mojica, et al. (article 5) as fifth because although it’s a systematic review from 2021 and had the larger sample size of all included studies, it focused on a variety of different treatments for knee osteoarthritis. Hyaluronic acid and platelet-rich plasma were among the included treatments but the results focused on comparison between many more options instead of just on the two treatment options I focused on.
I weighed the study by Raeissadat, et al. (article 6) as sixth. Being the only randomized clinical trial and not a systematic review or meta-analysis, his article is of the lowest level of evidence of all of the studies I chose on this topic. Regardless, I decided to include this article as it has been recently published in 2021, and focused on the two treatment options I am researching. The study followed patients for a year, allowing for proper assessment of clinical outcomes but it was performed outside of the United States, which may make the results less applicable to the U.S. patient population than the other studies included.
Magnitude of Effects:
Belk (Article 1): Eight studies reported P values on pre- to post-treatment scores within each group, 7 of which found PRP patients to improve significantly (P < .05) from pretreatment to latest follow-up and 3 of which found HA patients to improve significantly (P < .05) from pretreatment to latest follow-up. Six studies found PRP patients to report significantly better WOMAC scores (P < .05) at latest follow-up, while no studies found HA patients to report better scores. Pooled analysis from 5 studies with a mean follow-up of at least 12 months demonstrated that the PRP group had significantly better WOMAC scores as compared with the HA group (MD, 213.6 [95% CI, 218.2 to 29.1]; P < .0001). The I2 statistic for WOMAC scores was 81%, suggesting that moderate to high heterogeneity may be present. However, these statistics are greatly underpowered, making it difficult to draw strong inferences. Eleven studies reported results of the VAS score. Four studies1,16,33,39 found PRP patients to improve significantly (P < .05) from pre-injection to latest follow-up, and 1 study found HA patients to improve significantly (P < .05) from pre-injection to latest follow-up. Five studies found PRP patients to report significantly less pain (P < .05) at latest follow-up when compared with HA patients, while no studies found HA patients to report significantly less pain than PRP patients. Six studies reported results of the Subjective IKDC score. Four studies found PRP patients to improve significantly (P < .05) from pre-injection to latest follow-up, and 2 studies found HA patients to improve significantly (P < .05) from pre-injection to latest follow-up. Pooled analysis from 4 studies with a mean latest follow-up of at least 12 months demonstrated that the PRP group had significantly better Subjective IKDC scores than the HA group (MD, 6.7 [95% CI, 2.1-11.2]; P = .004)
Gong (article 2): A total of 2 studies reported WOMAC Total scores at 1 month after treatment. The heterogeneity test indicated that the homogeneity was good (I2 = 0%, MD = 1.33, 95% CI: 0.43– 2.23, P = .004 < .05); 2 studies reported WOMAC total scores at 6 months after treatment. The heterogeneity test indicated heterogeneity (I2 = 0%, MD = 4.79, 95% CI: 4.00– 5.59, P < .05); 3 studies reported WOMAC Total scores at 12 months after treatment. The heterogeneity test suggested a low degree of homogeneity (I2 = 0%, MD = 3.85, 95% CI: 2.66–5.04, P < .05). A fixed-effects model was used for meta-analysis. The subgroup analysis results showed that the WOMAC Total Score of the group receiving PRP compared with HA was statistically significantly different at 1, 6, 12 months after treatment. Several studies reported the subjective IKDC scores. The heterogeneity test suggested a high degree of homogeneity (I2 = 56%, 75%, 79%), and a random-effects model was used for meta-analysis. We can find that patients in the PRP group showed no significant difference in these scores than those in the HA group at 2 months (MD = 0.58, 95% CI: 5.78–4.62, P = .83), 6 months (MD = 6.51, 95% CI: 0.01–13.03; P = .05), and 12 months (MD=5.72, 95% CI: 5.16–16.59, P=.30). Two studies reported the EQ-VAS at 6months after treatment. The heterogeneity test suggested a high degree of homogeneity (I2 = 91%), and a random-effects model was used for meta-analysis. There was no significant difference between these 2 groups, and the results demonstrated that the PRP injections and HA injections were similar in treatment KOA (MD = 6.26, 95% CI: 2.76–15.27, P=.17).
Tang (Article 3): The pooled data indicated that, compared with the HA group, PRP injection was associated with a decrease of the WOMAC total scores at 1 month (SMD=−0.84, 95% CI −1.48 to − 0.20, P = 0.010), 6 months (SMD = − 1.14, 95% CI − 1.88 to − 0.40, P = 0.002), and 12 months (SMD = − 1.47, 95% CI − 2.23 to − 0.70, P = 0.000). Nevertheless, there was no statistically significant difference between PRP and HA injections at 3 months (SMD = − 0.13, 95% CI − 0.78 to 0.52, P = 0.686). Heterogeneity was significant among these pooled results (I2 = 87.6%, 92.0%, 95.1%, and 95.3%, respectively). The patients with PRP injection had better pain relief than those with HA injection at 1 month (SMD=0.42, 95% CI −0.45 to 0.15, P<0.05), 3 months (SMD=0.08, 95% CI −0.56 to 0.67, P<0.05), 6 months (SMD=−0.34, 95% CI −0.99 to 0.45, P<0.05), and 12 months (SMD = − 0.72, 95%CI − 1.06 to 0.41, P < 0.05). PRP injection was more effective than HA injection at 6 months (SMD = 8.65, 95% CI 1.75 to 15.23, P < 0.05). However, the pooled data suggested there was no significant discrepancy comparing PRP injection with HA injection at 2 months (SMD=−1.35, 95% CI −6.06 to 3.35, P>0.05) and 3 months (SMD = 5.25, 95% CI 0.34 to 0.05). PRP injection was more effective than HA injection for the Lequesne Index scores at 6 months (SMD = − 0.72, 95% CI − 1.95 to 0.56, P < 0.05). The pooled analysis demonstrated that PRP was associated with a reduction of the symptom (SMD = − 0.06, 95% CI − 0.55 to 0.59, P < 0.05), pain (SMD=−0.05, 95% CI −0.34 to 0.26, P< 0.05), activities of daily life (SMD = − 0.16, 95% CI − 0.43 to 0.34, P < 0.05) and sport (SMD = − 0.06, 95% CI − 0.31 to 0.42, P < 0.05).
Tan (Article 4): The number of adverse events in the PRP and HA groups was 109 of 970 participants and 84 of 938 participants, respectively. There was no significant difference in adverse events between the 2 groups (RR 1.21, 95% CI 0.95-1.54; P 1⁄4 .13). The analysis did not identify a significant difference between the PRP and HA groups after 1 month (MD e3.81, 95% CI e7.98 to 0.36; P 1⁄4 .07) of treatment. However, the subjects in the PRP group performed better than those in the HA group at 3 (MD e5.04, 95% CI e8.82 to e1.26; P 1⁄4 .009), 6 (MD e8.52, 95% CI e11.17 to e5.87; P < .00001), and 12 months (MD e10.52, 95% CI e13.77 to e7.27; P < .00001). The subjects in the PRP group performed better than those in the HA group at 6 (MD 7.67, 95% CI 3.91-11.43; P < .0001) and 12 months (MD 5.70, 95% CI 0.98-10.42; P 1⁄4 .005). There was no significant difference in Tegner scores between the 2 groups after 2 and 6 months of treatment. However, the PRP group improved more than the HA group at 12 (MD 0.34, 95% CI 0.01 to 0.66; p 1⁄4 0.04).
Mojica (Article 5): When comparing WOMAC scores among patients who received the same injection type at different follow-up points, the lowest scores (indicating best function) were seen at 4-6 weeks after CS injection, LMW-HA, and MMW-HA injections. The lowest relative WOMAC scores within the HMW-HA group and LP-PRP group were both 3 months post-injection. LR-PRP injection patients reported the best WOMAC scores after 1 year of follow-up relative to earlier time points. Of note, 1 year after LR-PRP injection demonstrated the lowest WOMAC score overall. It is also noted whether the difference is statistically significant as well as if it reaches minimal clinically important difference (MCID). The MMI again is observed throughout the injectables in the time from baseline to 4-6 weeks, except in the case of LR-PRP which sees the additional clinically significant improvement in functionality in the period from 4-6 weeks to 3 months. The lowest WOMAC scores (indicating best outcome) are achieved by LR-PRP. Of note, LR-PRP is also the only injection that after one year of follow-up continues to show improvement, unlike the other injection types which have regressed, typically reaching an inflection point between 4-6 weeks and 3 months. The lowest WOMAC scores (indicating best outcome) are achieved by LR-PRP.
Raeissadat (Article 6): In the 2 months post-injection evaluation, the ozone group had lower WOMAC, Lequesne, and VAS scores (better results) compared to other groups. The differences were significant in WOMAC (for Total score as well as Pain and Function sub-scores), and Lequesne (Total score and Pain sub-score). However, at the 6th month of follow up patients treated with HA, PRP, PRGF demonstrated better results based on WOMAC, Lequesne, and VAS compared to those cases treated with ozone. At this stage, the WOMAC (Total, and Pain and Function sub-scores); Lequesne (Total and ADL sub-score) and VAS scores were observed significantly higher in ozone group than the other groups (P < 0.05). In addition, in the 6th month of follow up, the VAS and WOMAC scores of the PRP and PRGF groups were lower than the HA group, however had somehow similar Lequesne scores. These differences though, were not found to be significant.
At the end of the 12th month, only PRGF and PRP groups had statistically significant differences from those treated with HA and ozone. The Total, Pain and Function scores of the WOMAC; the Total, Pain, and ADL scores of the Lequesne; and the VAS score were meaningfully lower in the PRGF and PRGF groups (P < 0.05) at the final timeline of this study. In the WOMAC Stiffness sub-score as well as in the Lequesne Walk sub-score, no significant differences were observed between the four groups 12 months after injection. Of note, no significant variation was observed within the study groups for WOMAC, VAS and Lequesne scores. Despite lower WOMAC, VAS, and Lequesne scores were observed at 2 month post-injection in all groups, these scores showed an increasing trend after the sixth months, which reaches its peak (near to the baseline) after 12 months. Although patients receiving ozone had the lowest scores 2 months after injection, they had a sharper increase in the later months and ended up with the highest scores among all groups. The patients of the four groups were compared regarding their satisfaction and complications after injection. Accordingly, PRP and PRGF groups had experienced more but not significant post injection pain. There was no significant difference between four groups in patient’s satisfaction.
Clinical Significance:
Knee osteoarthritis is a burden for many patients, causing pain and decrease in function that contributes to not being able to fully perform daily activities, affecting work, recreation, and general well-being. Fourteen million people in the United States have symptomatic knee osteoarthritis, with more than half of those being younger than 65 years of age. With oral medications being able to control symptoms for only a limited amount of time, patients often resort to intraarticular injections for symptom relief and improvement in function. Based on the above research, platelet-rich plasma injections appear to improve symptoms significantly more than hyaluronic acid and maintains this effect long-term. This has great significance clinically, as patients with better symptom control and improved function can present to their providers less often, experience better quality of life, and receive less injections than normally. While PRP injections are associated with a higher cost than hyaluronic acid, the longevity of symptom relief and better patient-reported outcomes balance the higher cost with less injections overall and may be a better option for patients whose symptoms are not well-controlled. Based on this research, I would recommend platelet-rich plasma injections to patients who are not achieving adequate symptom relief with hyaluronic acid injections as PRP is more likely to improve outcomes both the short-term and long-term.
Other Considerations:
The higher cost of platelet-rich plasma injections could be an obstacle to patients whose insurance will not cover the injections or who are not willing to pay out of pocket for the injection. While some patients may be willing to pay or change insurance to one that covers PRP injections, many will not have those options. A recent cost-effectiveness study from 2020 found PRP injections and hyaluronic acid injections to both be cost effective options for treatment of knee OA, but PRP were found to be less cost-effective than HA. However, the study concluded that in terms of quality and effectiveness at one year, PRP was a reasonable option as compared to HA despite higher price.
With more and more studies being done comparing PRP to HA we are consistently seeing that PRP significantly improves pain and function over HA. While it may take more time and education regarding PRP to institute it as standard treatment for knee osteoarthritis that is covered by insurance, the research so far is promising. More large, high level studies need to be performed to solidify PRP as an effective treatment and more providers need to consider this treatment as an option instead of always resorting to the traditional treatment involving hyaluronic acid injections.
https://pubmed.ncbi.nlm.nih.gov/32721546/
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