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. 2023 Aug 25;12(17):5541.
doi: 10.3390/jcm12175541.

Ultrasound-Guided Injections of HYADD4 for Knee Osteoarthritis Improves Pain and Functional Outcomes at 3, 6, and 12 Months without Changes in Measured Synovial Fluid, Serum Collagen Biomarkers, or Most Synovial Fluid Biomarker Proteins at 3 Months

Richard T Meehan  1 , Mary T Gill  1 , Eric D Hoffman  1 , Claire M Coeshott  1 , Manuel D Galvan  1 , Molly L Wolf  1 , Isabelle A Amigues  1 , Liudmila M Kastsianok  1 , Elizabeth A Regan  1 , James L Crooks  1   2 , Gregory J Czuczman  1   3 , Vijaya Knight  4
Affiliations

Ultrasound-Guided Injections of HYADD4 for Knee Osteoarthritis Improves Pain and Functional Outcomes at 3, 6, and 12 Months without Changes in Measured Synovial Fluid, Serum Collagen Biomarkers, or Most Synovial Fluid Biomarker Proteins at 3 Months

Richard T Meehan et al. J Clin Med. .

Abstract

Background: Prior studies have demonstrated improved efficacy when intra-articular (IA) therapeutics are injected using ultrasound (US) guidance. The aim of this study was to determine if clinical improvement in pain and function after IA hyaluronic acid injections using US is associated with changes in SF volumes and biomarker proteins at 3 months.

Methods: 49 subjects with symptomatic knee OA, BMI < 40, and KL radiographic grade II or III participated. Subjects with adequate aspirated synovial fluid (SF) volumes received two US-guided IA-HA injections of HYADD4 (24 mg/3 mL) 7 days apart. Clinical evaluations at 3, 6, and 12 months included WOMAC, VAS, PCS scores, 6 MWD, and US-measured SF depth. SF and blood were collected at 3 months and analyzed for four serum OA biomarkers and fifteen SF proteins.

Results: Statistical differences were observed at 3, 6, and 12 months compared to baseline values, with improvements at 12 months for WOMAC scores (50%), VAS (54%), and PCS scores (24%). MMP10 levels were lower at 3 months without changes in SF volumes, serum levels of C2C, COMP, HA, CPII, or SF levels of IL-1 ra, IL-4, 6, 7, 8, 15, 18, ILGFBP-1, 3, and MMP 1, 2, 3, 8, 9. Baseline clinical features or SF biomarker protein levels did not predict responsiveness at 3 months.

Conclusions: Clinical improvements were observed at 12 months using US needle guidance for IA HA, whereas only one SF protein biomarker protein was different at 3 months. Larger studies are needed to identify which SF biomarkers will predict which individual OA patients will receive the greatest benefit from IA therapeutics.

Keywords: biomarkers; cytokines; osteoarthritis; synovial fluid; ultrasound.

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Conflict of interest statement

The pneumatic compression device (KneeTapTM) used in the study was granted US patent #7468048 to R. Meehan in 2008, with NJH as the owner. Subsequently, Arthroventions LLC was granted a license from NJH to commercialize this device. E. Hoffman and R. Meehan were co-founders of Arthroventions LLC. No other potential COI exists for any other authors, and this potential COI is managed each year by NJH VP/Chief Compliance Officer, Legal, and Regulatory Affairs, Alicia Christensen, JD, christensena@njhealth.org.

Figures

Figure 1
Figure 1
(A) An inflated pneumatic compression device with an image displayed on an ultrasound screen prior to successful knee aspiration of synovial fluid. Image courtesy of Dr. R. Meehan and Dr. R. Scheuring. (B) US image of a study subject during needle insertion, displaying a bright 20-gauge needle entering from the upper right-hand corner of the image with the tip placed within the intra-synovial space (dark anechoic region) during inflation and prior to injecting IA HA product.
Figure 2
Figure 2
Subject participation, timeline of study visits, and reasons for withdrawals.
See this image and copyright information in PMC

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