Platelet-rich plasma injection fails to top placebo for pain, joint benefit in knee OA
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Platelet-rich plasma injections failed to improve knee osteoarthritis symptoms or joint structure at 12 months, compared with a saline placebo, in patients with symptomatic, mild-to-moderate radiographic disease, according to data.
“The use of platelet-rich plasma (PRP) for the treatment of knee osteoarthritis is increasing, but most clinical guidelines do not currently recommend it due to the lack of high-quality evidence,” Kim L. Bennell, PhD, of the University of Melbourne, in Victoria, Australia, told Healio Rheumatology. “Also, there is much interest in being able to identify a treatment that not only improves symptoms but also slows structural disease progression. Our study was important to provide robust evidence about the effectiveness of a PRP product on both of these outcomes to inform clinical practice.”
To examine the effects of intra-articular PRP injection on symptoms and joint structure in patients with symptomatic, mild-to-moderate radiographic knee OA, Bennell and colleagues conducted a randomized, placebo-controlled blinded study. The researchers enrolled 288 participants in Sydney and Melbourne, aged 50 years or older with symptomatic knee OA, from Aug. 24, 2017, to July 5, 2019. Participants were randomly assigned 1:1 to receive three weekly intra-articular injections of either leukocyte-poor PRP or saline placebo.
The 12-month follow-up period ended July 22, 2020. The primary outcomes were 12-month change in overall average knee pain scores — based on a scale of 0-10, with higher scores indicating worse pain, and a minimum clinically important difference of 1.8 — and the percentage change in medial tibial cartilage volume, assessed via MRI. A total of 31 secondary outcomes examined pain, function, quality of life, global change and joint structures at 2 and/or 12 months. Both treatment groups had 140 individuals receive all three injections, with a total of 269 completing the trial.
According to the researchers, who published their findings in JAMA, PRP resulted in a mean change in knee pain scores of –2.1 points, compared with –1.8 for placebo, at 12 months, resulting in a difference of –0.4 points (95% CI, –0.9 to 0.2). The mean change in medial tibial cartilage volume, meanwhile, was –1.4% for PRP, compared with –1.2% for placebo, resulting in a –0.2% difference (95% CI, –1.9% to 1.5%). Among 31 secondary outcomes, 29 failed to demonstrate any significant between-group differences.
“The PRP tested did not show any greater benefits for improving pain or function than saline injections, nor did it change knee joint structure in people with mild-to-moderate knee osteoarthritis,” Bennell said. “Our results do not provide evidence to support the use of PRP for the treatment of knee osteoarthritis.”
“As PRP preparations are highly variable, we cannot necessarily generalize our results to all PRP preparations,” she added. “In line with person-centered care, the current evidence, risks and costs of various treatments for osteoarthritis, including PRP, should be outlined so that the patient can make an informed decision about their management.”
Perspective
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Because knee OA is such a major health issue, and because so far, the only real “disease-modifying therapy” for this condition is arthroplasty, numerous and varied modalities have been tried. From glucosamine and chondroitin supplements to external electromagnetic waves, to hyaluronic acid (HA) injections, to the current infatuation with platelet-rich plasma (PRP) injections; nothing has really shown meaningful efficacy.
Scour the literature – and you don’t have to try very hard – and you will find numerous trials of PRP vs. placebo, vs. corticosteroid injections, vs. HA or even some in combination for knee OA. The quality of the studies varies and is often not very good. There are some meta-analyses.
Bottom line: PRP seems to be better than placebo and other injectables in terms of pain and function. The magnitude of the differences is mostly small, and most trials show short term only results. And keep in mind, “PRP” is not one thing: Preparations and procedures (and therefore) content and biological activity varies from study to study, and even between patients.
Moreover, the actual biological effects of the PRP have not been rigorously studied from an immunologic standpoint. The anatomic effects have also not been well studied to-date, specifically the effects of PRP injections on the “target-organ”: Articular cartilage. Cost-effectiveness analyses have also not shown benefit from PRP in knee OA.
Surprisingly, Bennell and colleagues reported on a quite rigorous and well-designed trial; perhaps less surprisingly, no difference was seen between PRP and placebo at 6 months in terms of pain or function. Although this study did something unique by measuring medial tibial cartilage volume by MRI, with patients selected as having medical compartment OA, unfortunately, no difference was found.
Does this study spell the end of PRP treatments for knee OA? Of course not. It does appear to be safe and to give some relief of symptoms, and as PRP is typically not covered by insurance, providers and patients are free to try it as they wish, but the Holy Grail it is not.
Perspective
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With over 260 million patients worldwide affected by knee osteoarthritis, looking for treatment options is discouraging. Since there are no DMARDs approved yet and surgical intervention has minimal benefit, options like platelet-rich plasma (PRP) seemed like a sure bet.
PRP contains elevated concentrations of growth factors and cytokines that promote healing and slow the destructive processes. Unfortunately, the results are not what we were hoping to see and no studies to date have shown any real improvement for our osteoarthritis patients. In our area, insurance companies will not cover the costs due to the lack of data proving the efficacy as well as the lack of FDA approval. It is charged as a fee-for-service offering and must be paid at the time of the procedure. Fees for PRP injections range from $1100 to $1300 per injection.
In my practice, orthopedic physicians donated their time and significantly reduced the costs associated with PRP to see if this could help their patients. The few patients that tried this modality, sadly, did not receive any benefit. While PRP is still being advertised as a treatment option for osteoarthritis, future studies may find the exact patients who will benefit from this therapy.
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David A. McLain, MD, MACR, FACP, FRCP
In clinical medicine, platelet-rich plasma (PRP) has been used in oral maxillofacial surgery, plastic surgery, dermatology, orthopedics, cardiac surgery, urology, pediatric surgery, gynecology and ophthalmology, as well as “regenerative medicine”. In orthopedics, PRP is used for tendon, cartilage and bone repair.
PRP is rich in growth factors. Proper preparations can help PRP secrete many growth factors at high concentrations, including vascular endothelial growth factor, transforming growth factor-beta, insulin-like growth factor, platelet-derived growth factor and epidermal growth factor.
The benefit of using PRP is that it is an autologous biologic material that elicits a minimum risk of immune reactions and transmission of infectious and contagious diseases. The best results have been seen in wound healing. However, the negative side to PRP is that it is a biologic material that is prepared under a few dozen different described protocols, using various methods to stimulate growth factors, so the exact composition of growth factors and other components varies.
Moreover, there are several studies, including this one, that report no benefit from its use. Additionally, insurance does not cover PRP as it is not FDA-approved and considered experimental. The cost may run up to $1000 out-of-pocket for treatment. Growth factors are being purified and presumably available for clinical use (although not FDA-approved). There is also research being conducted on using PRP and growth factors combined with stem cells. There may be a future for these treatments, but more research is needed.
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