Knee Osteoarthritis Pain Management with an Innovative High and Low Molecular Weight Hyaluronic Acid Formulation (HA-HL): A Randomized Clinical Trial

Abstract

The objective of this study was to compare a single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) versus placebo in treating moderate-to-severe symptomatic knee osteoarthritis. Subjects with primary osteoarthritis knee pain (Kellgren and Lawrence grade 2–3) were randomly assigned to intra-articular HA-HL or placebo in a prospective, double-blind, 24-week study. The primary outcome variable was change from screening to week 24 of a Visual Analogue Scale (VAS) pain score. Secondary outcomes included Lequesne’s algofunctional index, EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L), Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) response and rescue medication usage. In a total of 692 randomized patients, a rapid decrease was observed in mean VAS pain score from baseline to week 1 (26\u2009±\u200924 mm in the HA-HL group vs. 23\u2009±\u200923 mm in the placebo group); pain intensity continued to decrease during 24 weeks of follow-up, reaching a mean change from baseline of 35\u2009±\u200928 mm vs. 32\u2009±\u200927 mm at week 24. Mixed model analysis demonstrated statistically significant differences between groups in favor of the HA-HL group at weeks 1, 6, 12, and 24. HA-HL was also more effective than placebo in improving Lequesne’s algofunctional index, OMERACT-OARSI response, and health-related quality of life. The use of rescue medication (paracetamol 500 mg tablets;\u2009≤\u20096 per day) was lower in the HA-HL group. Both treatments were similarly well tolerated. A single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) is effective in providing fast, sustained, and clinically relevant reductions in pain, functional limitation, and health-related quality of life that were apparent at 1 week after the intra-articular injection and maintained throughout the 24-week follow-up in subjects with painful knee osteoarthritis, with a good safety profile. ClinicalTrials.gov identifier: NCT03200288.