The study provides proof-of-concept evidence concerning the feasibility and safety of PA-PRP injections necessary to inform a larger clinical trial in people with knee osteoarthritis. PA-PRP improved self-reported pain, symptoms and lower extremity function, however no between-group differences were found.

Knee is one of the most commonly affected joints caused by osteoarthritis (OA) which is a prime cause of musculoskeletal pain worldwide, with prevalence expected to increase with an aging and obese population and chances of total knee replacements are forecasted to increase by 600% approx. over the next 25 years. However, no effective therapy is available for OA, so main focus is laid on symptomatic relief with the purpose of reducing pain and disability and maintaining or improving joint mobility. Although, there are many non-surgical treatments and drug treatments such as simple analgesics and non-steroidal anti-inflammatory drugs are available, but these are not very much effective. Furthermore, it is not possible to rely on intra-articular injections with hyaluronic acid (HA) for the treatment of knee OA because efficacy is variable and ongoing treatment is required. Improvements in knee OA symptoms with platelet-rich plasma (PRP) have been attributed to its ability to modify intra-articular inflammatory processes. Photo-activation of peripheral blood also improves inflammatory mediators associated with OA, however combined photo-activated PRP (PA-PRP) has not been investigated.

Rationale behind research

• To date, only two case studies have investigated combined photo-activation and PRP (PA-PRP) in degenerative conditions, reporting symptomatic improvements in one patient with a chondral defect and another with knee OA. There are currently no clinical trials of PA-PRP in knee osteoarthritis.
• Therefore, the single center, double blind, randomized controlled pilot study was conducted to evaluate the effectiveness of intra-articular injections of PA-PRP compared to hyaluronic acid in treating mild to moderate knee OA

Objective

To determine the feasibility, safety and changes in pain, symptoms and lower limb functional ability using intra-articular injections of PA-PRP compared to hyaluronic acid (HA) in patients with mild to moderate knee OA.

Study outcomes

• To evaluate symptom severity, participants first completed a 100 mm Visual Analogue Scale (VAS) to rate their average knee pain over the previous week, with terminal descriptors of “no pain” and “worst pain” possible
• To document self-reported symptoms, participants completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Knee Quality of Life 26-item questionnaire (KQoL-26). The KOOS uses a five point Likert scale for scoring the three Western Ontario and McMaster Universities Osteoarthritis (WOMAC) sub-scales of Pain, Stiffness and Physical Function, with the additional inclusion of the sub-scales Quality of Life and Sport and Recreation. KQoL-26 is comprised of three sub-scales, including Physical Functioning, Activity Limitations and Emotional Functioning, and uses a five point Likert scale for scoring.
• Two objective measures of lower extremity functional ability (maximum single leg hop and number of knee bends in 30 s) were also completed by participants

Time points:  Baseline, 4th week and 12th week

Baseline: There were no differences between the two groups at the baseline.

Outcomes

• Average pain recorded using the 100 mm VAS reduced from baseline at the four and 12 week follow up time points for both the PA-PRP and HA groups. Post hoc tests showed that the reduction in pain at four weeks was significantly less than baseline (27.67 mm, 95 % CI 12.39 to 42.95, p = 0.003, ETA = 0.686), however the 11.4 mm reduction in VAS at 12 weeks was not statistically significant in PA-PRP group. No significant reductions in pain were found for the HA group.

• For the PA-PRP group, significant improvements were found at both follow up time points in the KOOS Pain subscale (4 weeks: 13.33, 95 % CI 4.66 to 22.01, p = 0.007;  12 weeks: 11.67, 95 % CI 2.99 to 20.34, p = 0.014, ETA = 0.624), the KQoL-26 Physical subscale (4 weeks: 8.50, 95 % CI = 1.84 to 15.16, p = 0.018; 12 weeks: 9.33, 95 % CI 4.56 to 14.11, p = 0.002, ETA = 0.706) and the KQoL Emotional subscale (4 weeks: 12.08, 95 % CI 3.26 to 20.91, p = 0.013; 12 weeks: 9.58, 95 % CI 17.11 %, p = 0.009, ETA = 0.715). For the HA group, significant improvements were only found in the KOOS Function subscale at 12 weeks (14.05, 95 % CI 18.59 to 24.15, p = 0.008, ETA = 0.602).
  

• PA-PRP group significantly improved both hopping (4 weeks: 13.44, 95 % CI = 2.23 to 24.66, p = 0.025; 12 weeks: 22.33, 95 % CI 11.86 to 32.80, p = 0.001, ETA = 0.799) and knee bend (12 weeks: 9.78, 95 % CI 5.00 to 14.56, p = 0.002, ETA = 0.756) performance, whereas changes in physical function in the HA group were not found to be significant. No significant between-group differences were found for any of the self-reported measures or for either of the functional tests (p > 0.05).
  

This was a double-blind randomized controlled pilot study comparing intra-articular injections of a novel form of PRP activated with ultraviolet light compared to HA. The results demonstrate the feasibility of this technique in people with knee OA and show no serious adverse events were reported. There was a significant decrease in VAS, significant improvements in the KOOS Pain subscale, KQoL-26 Physical and Emotional subscales at four and 12 weeks and also improved performance on the functional measures of hopping and knee bend at 12 weeks.

Previous RCTs have investigated the efficacy of PRP compared to HA or saline however to our knowledge this is the first to objectively evaluate lower limb function and the only one to use photo-activation of PRP. Photo-activation of peripheral blood has been previously shown to improve the inflammatory cytokine profile of healthy adults and people with psoriasis, and therefore has the potential to improve outcomes in OA where pro-inflammatory cytokines are critical mediators in the pathophysiology of the disease. Combined with PRP, which releases growth factors and other proteins responsible for tissue repair and inflammatory modulation, this may offer a novel method for improving symptoms and function in people with knee OA.