Long-term functional and clinical outcomes of intraarticular double-cross-linked high molecular weight hyaluronic acid (Crespine Gel Plus) injection in knee osteoarthritis: a one year prospective study

TL;DR

A single injection of Crespine Gel Plus hyaluronic acid provides lasting pain relief and improved function for knee osteoarthritis patients over 12 months.

Contribution

This study provides robust 12-month clinical data on the effectiveness of double-cross-linked hyaluronic acid in knee osteoarthritis.

Findings

Adjusted KOOS4 scores improved significantly at both 3 and 12 months post-injection.

VAS pain scores decreased significantly at both 3 and 12 months.

Improvements in pain, symptoms, and quality of life were maintained over 12 months with no major adverse events.

Abstract

Knee osteoarthritis (OA) causes substantial pain and disability. Double cross-linked, high-molecular-weight hyaluronic acid (HMWHA; Crespine Gel Plus) may extend symptom relief beyond the typical 3 to 6 month horizon, but robust 12-month data remain limited. This study aimed to evaluate short- and long-term outcomes over 12 months following a single Crespine Gel Plus injection in routine care.

Prospective single arm cohort at a Malaysian Hospital from June 2023 to June 2025. Adults with radiographically confirmed knee OA (Kellgren–Lawrence [KL] grades I–III, or IV if declining surgery) received a single 2 mL intra-articular injection. Outcomes were KOOS4 (primary; 0–100, higher = better) and VAS pain (0–10; higher worst) along with KOOS4 Subscales. Assessments were at baseline, 3 months, and 12 months. Linear mixed-effects models (participant random intercepts; REML; Satterthwaite dfs) adjusted for age, gender, BMI, and KL grade.

Of 111 participants (mean age 65.1 ± 7.8; 66.6% female; BMI 28.2 ± 4.9 kg/m2), 107 (96.4%) completed 3-month follow up and 92 (82.9%) completed 12-month follow up. Adjusted KOOS4 improved by 8.59 points (95% CI 5.48–11.69) at 3 months and 8.78 (5.51–12.05) at 12 months (both p < 0.001), exceeding customary minimal clinically important differences (MCIDs). VAS decreased by 1.68 points (-2.03 to -1.33) at 3 months and 1.64 points (-2.01 to -1.27) at 12 months (both p < 0.001). KOOS Pain, Symptoms, ADL, and QoL improved at at 3 and 12 months, with small, non-significant changes between 3 and 12 months. Higher BMI predicted worse adjusted KOOS outcomes; age and KL grade were not significant predictors. No major adverse events occurred.

A single injection Crespine Gel Plus was associated with clinically meaningful improvements in pain and function that emerged by 3 months and were maintained to 12 months, with a favourable tolerability profile.

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