ULTRASOUND GUIDED INJECTIONS of HYADD4 for KNEE OSTEOARTHRITIS IMPROVES PAIN and FUNCTIONAL OUTCOMES at 3 and 6 MONTHS WITHOUT CHANGES in SYNOVIAL FLUID VOLUMES

ABSTRACT

Background: Prior studies have demonstrated improved accuracy and efficacy when Intra-articular (IA) therapeutics are injected using ultrasound (US) guidance. There is also growing evidence that many patients with knee oste-oarthritis (OA) exhibit a pro-infammatory catabolic synovial fuid (SF) profile. However, it is not known if temporary clinical improvement in pain and function after IA Hyaluronic acid (HA) injections is associated with changes in SF volumes. Objectives: The purpose of this study was to determine if IA HA injections delivered using US directed needle visualization with an external pneumatic compression device would result in improved clinical outcomes for knee OA at 3 and 6 months, and if this was associated with a reduction in the amount of knee synovial fuid (SF) measured on US. Methods: 49 eligible subjects with symptomatic Knee OA, BMI < 40 and KL radiographic rating of II or III OA were consented for this open label prospective IRB approved Investigator Initiated SF OA biomarker study (HS 3179, NCT 04093232). All standing radiographs were reviewed by a fellowship-trained MSK radiologist. 36 subjects had adequate aspirated SF volumes of > 500 mcl for biomarker analysis and therefore were eligible to receive two IA injections of HYADD4, 24 mg/3ml (Fidia Farmaceutici S.p.A. Italy) 7 days apart by a MSK US certifed Rheumatologist. An external pneumatic compression device and US visualized needle insertion ensured injections were delivered into the intra-syn-ovial space. Despite COVID-19 restrictions, 34 patients (17 women and 17 men) between 35 and 78 years of age returned for 3 month evaluations and 30 had evaluations at 6 months. The following clinical variables were measured Western Ontario and McMaster Universities Index (WOMAC) total scores, Visual Analog Pain Scale (VAS, 0-10), PCS scores on the SF-36 health survey questionnaires (physical function/bodily pain and general health), 6-min-ute walking distance in meters (6 MWD), and measured SF depth before and after an external pneumatic compression device was infated to 100 mmHg to facilitate aspiration by increasing available SF volumes under positive presure. The SF depth was measured on the recorded US image (GE logiq e) as the largest anechoic region selected for aspiration on either the lateral (n= 30) or medial (n=4) compartment. SF and simultaneous peripheral blood samples were centrifuged and cryopreserved at-80 o C within 45 minutes of aspiration for future analysis. Statistical differences between baseline values compared to those levels at 3 and 6 months were determined using a paired ANOVA test with p <0.05 signifcance. Results: Improvements over baseline values were observed at 3 and 6 months respectively, after IA HA injections in WOMAC (40%, 40%), VAS (45%, 51%) and PCS (15%, 18%) all p< 0.0001. The 6 WWD improved by 7 % at 3 months (p< 0.007) but was not statistically improved at 6 months. US measured SF depth at baseline was 3.2 ± 2.2 mm before infation and 6.4 + 3.7 mm after infation of the pneumatic external compressioin device but statistical differences in SF depth were not observed at 3 and 6 months. Conclusion: Despite improvements in WOMAC, VAS scores, and PCS scores on the SF 36 at 3 and 6 months after US guided knee injections with an HA product, a statistically signifcant reduction in the amount of US measured SF was not observed. The 6 MWD improved at 3 months but was not statistically different from the baseline distance by 6 months. IA injections using US needle visualization confrmed that the product was delivered into the synovial space with 100 % accuracy which might have resulted in improved efficacy results in this study compared to prior IA HA studies injected without US or using different HA products. In the future, we hope SF biomarkers may identify which individual OA patients will likely achieve the greatest beneft with IA HA injections and to determine if this is associated with a reduction in catabolic pro-infammatory proteins.