by Pam Harrison
Contributing Writer, MedPage Today
April 16, 2016
Injection of autologous conditioned plasma (ACP) into the knee joint of patients with osteoarthritis (OA) resulted in significant improvement on all measures of pain, stiffness, and physical function and had no adverse effects, a randomized, double-blind trial found.
In a small study involving a total of 30 patients, a series of three weekly intra-articular ACP injections led to a 78% improvement from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at 12 months compared with a 7% improvement for placebo controls, according to Patrick A. Smith, MD, of the Columbia Orthopaedic Group, in Columbia, Mo.
“The primary objective of the current study was to determine the safety of ACP, and the secondary objective was to determine the efficacy of ACP in patients with primary OA of the knee,” Smith wrote in American Journal of Sports Medicine.
“The results confirmed the study’s hypothesis that no differences were present for outcomes related to patient safety, while significant improvements related to efficacy between ACP and placebo groups were present throughout the study duration,” he stated.
The study was sanctioned by the Food and Drug Administration (FDA) and was the first trial designed specifically to assess the safety and efficacy of intra-articular, platelet-rich plasma (PRP) injections for the treatment of knee OA. As Smith noted, PRP injections are appealing to patients because treatment is derived from their own blood and does not rely on exogenous products such as hyaluronic acid.
All patients were randomized to three treatment visits, 1 week apart, followed by three follow-up visits, the last visit being at 12 months after receiving the first injection.
The investigational arm received three intra-articular injections of 3 to 8 mL of ACP at 1-week intervals, while the control group received three intra-articular injections of saline on the same schedule.
“All patients in both groups had their blood drawn and spun for ACP procurement during each injection visit,” Smith observed.
He explained that ACP is spun only once for 5 minutes, so the preparation time to obtain the amount of ACP needed to inject the knee joint was under 20 minutes per session. The preparation used in the study was a leukocyte-poor ACP product, and processing results in a pure substance that can be injected back into the joint space.
“The lower overall WOMAC scores for the ACP group were statistically different from the WOMAC scores for the placebo group starting at 2 weeks [P=0.016],” Smith reported. “And a statistically significant decrease in WOMAC scores when compared with baseline was seen in the ACP group starting at 1 week [P=0.005], and the decrease remained statistically significant throughout the study duration.”
For example, on the pain component of the WOMAC score, ACP recipients dropped from a baseline score of 10 to a score of 2 at 12 months – a 76% decrease in pain from baseline – while placebo patients dropped only 2 points from a baseline score of 11 to a score of 9 at 12 months, for a 19% reduction in pain from baseline.
Similarly, those treated with ACP injections dropped from a baseline score of 4 on the stiffness component of the WOMAC score to a score of 1 at 12 months, or a 77% decrease in stiffness from baseline, while there was no change from baseline to 12 months in the stiffness component among placebo controls.
The physical function component of the WOMAC score also dropped by 78% among ACP recipients from a baseline score of 32 to a score of 7 at 12 months. Again, there was virtually no change in measures of physical function at 12 months among placebo patients.
There also was a statistically significant decrease in the overall WOMAC score at 2 months among placebo patients (P=0.015) — “suggesting some placebo effect,” Smith noted.
“However, this was the only time point that remained statistically significant, with a slight improvement from baseline,” he added.
“[And] the complete absence of adverse events associated with the ACP injection indicates that the injection is safe for human treatment.”
A potential limitation of the study was the small sample size, which was mandated by the FDA, as well as the use of saline as a placebo control instead of hyaluronic acid or steroids.
Again, however, the FDA mandated saline to be used as placebo in the study so as to arrive at a realistic comparison of the effects of ACP.
Carlos Meheux, MD, of Houston Methodist Hospital told MedPage Today that several level-1 evidence studies have demonstrated that PRP injections do have significant benefit in terms of improving pain and functionality in patients who have received these injections for treatment of OA of the knee.
“Studies have also compared PRP with hyaluronic acid as well as placebo, and what these studies have shown is that PRP does better than comparators to improve functionality and symptoms,” he added.
Treatment response after only a few injections of PRP also appears to be durable, lasting at least 6 months, and in a few studies out to 1 year.
“Given the increasing incidence of OA, I think more treatment options, especially non-operative treatment options, is a great thing, and I think these injections will change the direction towards a non-operative approach to OA,” Meheux said.
He explained that the platelet-derived product used for these intra-articular injections contains a number of growth factors which the body uses to regenerate tissue and diminish inflammation, thereby alleviating symptoms.