»» Thank you. So I'm going to talk about treatment of early to moderate knee osteoarthritis with autologous platelet-rich plasma. I have no conflicts to disclose. So I get asked a lot, does PRP treatment work for knee osteoarthritis? And today, in 2021, there are more than 30 randomized controlled trials in the literature most commonly comparing platelet-rich plasma injections with hyaluronic acid injections. Jason Dragoo and his group and Eric McCarty recently did a meta-analysis of 18 Level 1 studies. And we heard yesterday from Elisabetta Kahn about several more studies done internationally. Generally these studies are not perfect and they're pretty variable in how many PRP injections are given, what the comparator group is. But generally, improved outcomes over hyaluronic acid have been seen. And there's a general opinion that a leukocyte-poor formulation may be better. And so I'm going to give you preliminary results from a federally funded study that is still ongoing, where we're looking at patients with early to moderate knee osteoarthritis. How is this defined? Kellgren-Lawrence grade of no more than 3. They could have Kellgren-Lawrence grade 0. If so, they will need MRI or arthroscopic evidence for either degenerative meniscus or chondral pathology. We're also recruiting patients who report pain at least 4 out of 10. Now our clinical outcomes include patient-reported outcomes, a formal gait analysis, proteomic assessment and MRI-T2-MAP. The patient-reported outcomes and gait analyses, we are getting at baseline, 1 month, 3 months and 6 months after the PRP treatment series. So it's a 3-injection series. The gait analysis is also done at the same time points. And we've collected a sample of every PRP injection given along with the baseline blood and bank that. And we're obtaining MRI scans at baseline and at the 6-month follow-up. And so preliminary analysis is of the first 30 subjects who have completed all the parameters. We did have 100% follow-up. And so I know many people say, I know this works. My patients tell me it works. And what we found, the changes to the mean WOMAC were improved through 6 months in all of the three subscales, pain, stiffness and function. So looking at things on average, we did find improvement. Functional improvement was also seen with pretty strong correlations between the patient-reported outcomes and what we found with loading, stride length and gait speed in our formal gait analyses. And so those who had the positive responses to treatment also had objective increases in joint loading. And so if the movies work, I'm going to show you here on the left, this is a representation of the gait study prior to treatment from one of our patients. And on the left, or on the right, this is him at 6 months after his PRP treatment. And you can clearly see improvement in his walking parameters. Now the PRP response was variable. So if you take a 20-point change as your minimally clinically important difference, then we started to find that only about a third of patients met this criteria for improvement. Slightly over half of the patients were in this range where there were some changes, but they did not meet that criteria. And 7% of the patients actually worsened after 6 months. And one of the things that we are intending to look at with this study is whether we could identify responders based on their proteomics. And so preliminary analyses of this data where we did principal component analyses, plotting this again against a multiplex evaluation of cytokine, of 30 cytokines, we did come up with three cytokines that did seem to drive the pain scores. And so we will certainly evaluate this further. Our cohort is now pushing, it's more than double what I'm reporting here. And we'll see if these three cytokines continue to show some interest. And we'll follow this up with larger evaluation. Now the other major question is, did you find any regenerative effects? And to evaluate this, this is where we used quantitative MR. Specifically we used the T2 map. And so in general, when we find an increase in T2 map, this suggests that there is increase in cartilage degeneration. And so what we did find was that, yes, patients felt better and they started loading their joints more. But the greater loading actually correlated with increasing MRI T2 values suggestive of cartilage damage in some areas of the knee. And so in conclusion, the main WOMAC, we showed sustained improvement in patients with early to moderate knee OA through the 6-month follow-up period. About one-third showed a clinically meaningful level of pain and symptomatic relief. We found that improved WOMAC correlated to gait improvements. And the gait study really argues against that this is purely due to a placebo effect. There did appear to be a responder group. Those who felt better at 1 month also felt better at 6 months. As the 1 and 6-month WOMAC scores were highly correlated. However, this was a pre-post study. So we are studying all of the patients that did receive PRP treatment. This was a federally funded project, so no one had to pay for their PRP or any of the assessments. And so what that means is, with no comparator group, when you're looking at an early to moderate OA situation, the symptoms naturally wax and wane and can improve without treatment. And so we will need to do follow-on studies to see if this is truly due to the platelet-rich plasma treatment. And of course, we did not show signs of regenerative effect. And there may be, so follow-on to that beautiful study from Cassandra, there may be issues with loading and osteoarthritis that we'll need to look at further. So thank you for your attention. »» Thank you.

knee osteoarthritis

PRP

hyaluronic acid

patient-reported outcomes

cartilage damage