A nail in the coffin for PRPs in knee OA?

5 minute read

The latest – and largest ever – study of PRPs in knee OA has been hoped by some to be the death knell for the therapy. But others are not yet ready to give up on it.

Platelet-rich plasma injections are no better than placebo at reducing knee pain or slowing disease progression in knee OA, according to an Australian trial that sought to overcome clear weaknesses in past studies.

The largest trial of its kind to date, the RESTORE trial randomised 288 adults with mild to moderate radiographic knee OA and found PRP injections were no more efficacious than saline for symptom relief at 12 months. Findings were published in JAMA.

“As more high-quality trials are being conducted for PRP in OA, we are finding no meaningful benefit of PRP when compared with placebo,” Dr Shirley Yu, a rheumatologist at Royal North Shore Hospital and co-investigator of the RESTORE trial, told Rheumatology Republic.

It follows two recent randomised controlled trials that also found PRP therapy provided no benefit for ankle osteoarthritis and Achilles tendinopathy over placebo or sham injections, and a Cochrane review which concluded PRP injections “probably provide little or no clinically important benefit for pain or function” of lateral elbow pain.

As a result, experts said PRP injections should no longer be offered to patients in place of proven management options for OA, such as exercise and lifestyle modifications.

Trial participants received three injections of either a commercial PRP product or saline, spaced a week apart, and reported changes in pain severity and quality of life during follow-up. MRI scans measured cartilage loss and all participants, injecting radiologists and assessors were blinded to treatment groups.

Pain scores improved by over 30% in both groups, although there was no significant difference between PRP treatment and the placebo group in terms of pain relief, symptoms or joint structure at 12 months.

Co-investigator Professor David Hunter of the University of Sydney’s Institute of Bone and Joint Research said the findings suggest PRP treatment “does not merit its expense nor potential harms.”

“Our results, suggesting no difference between placebo and PRP for pain or cartilage thickness, would suggest that prior positive findings may have been due to bias,” stemming from a lack of blinding and incomplete outcome data, Professor Hunter said.

Rheumatologist and trial co-investigator Professor Rachelle Buchbinder, of the Monash-Cabrini Department of Musculoskeletal Health and Clinical Epidemiology in Melbourne, said PRP treatments should no longer be offered to people with OA.

“When they are, those offering this treatment should clearly explain the evidence so that patients can make an evidence-informed decision,” she said.

“Caution before dismissing PRP entirely for knee OA”

Professor Haxby Abbott, a clinical epidemiologist at the University of Otago, New Zealand, said the RESTORE trial enrolled more participants than any prior study and provided “high-quality evidence” that PRP treatments were not effective for treating knee OA.

“This result does carry more weight than the earlier, flawed trials of PRP for knee osteoarthritis,” said Professor Abbott, who was not involved in the study.

Professor Abbott noted that many past trials compared PRP with other treatments, namely hyaluronic acid and corticosteroid injections “that themselves have very shaky evidence of effectiveness” with “very, very few placebo-controlled studies” done to date.

However, he said the RESTORE trial may not alone provide definitive evidence denouncing PRP injections until another large, well-designed, well-controlled trial replicates the findings.

Also hesitant to write off PRP therapy was Professor Jeffrey Katz, of Brigham and Women’s Hospital, Boston.

Professor Katz noted in an accompanying editorial that while the RESTORE trial found no benefit in PRPs over placebo for primary outcomes, “the suggestion of possible benefit for some of the secondary outcomes (self-reported improvement in pain and function), as well as the mixed results of prior studies, support caution before dismissing PRP entirely for knee OA.”

In the context of those inconsistent results, possibly down to varying PRP preparations and delivery protocols, Professor Katz concluded, “Until a new generation of trials using standardized approaches to PRP therapy provides evidence of efficacy, it would be prudent to pause the use of PRP for OA and Achilles tendinitis.”


Reviews and meta-analyses subject to methodological flaws

Previous trials using a variety of preparation methods have yielded mixed results and spawned numerous systematic reviews and meta-analyses, some of which have reported PRP injections can help to relieve pain, alleviate symptoms and improve self-reported function of knee OA.

Professor Buchbinder is conducting a living Cochrane review of blood product injections including platelet-rich plasma for knee OA, due to be completed early next year.

She said systematic reviews examining the evidence for PRP injections for OA outweigh the number of high-quality trials and were plagued by methodological issues.

“There is a wide range of quality among the many reviews,” said Professor Buchbinder. “Many of them have methodological issues that indicate their conclusions may not be valid.”

Moreover, surveying the evidence highlights the potential of systematic reviews and meta-analyses to amplify trial data of variable quality in the absence of rigorous trials.

“Meta-analyses can amplify biased results when they include small, low-quality trials with high risk of bias,” Professor Abbott said.

“This is exacerbated by ‘publication bias’ in which similar small, low-quality trials that show no treatment effect are either not submitted for publication or cannot find a journal to publish in.”

JAMA 2021, Online 23 Nov

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