Comparative Efficacy and Safety of Two Different Formulations of Linear Hyaluronic Acid in Patients with Knee Osteoarthritis
Abstract
1. Introduction
2. Results
2.1. Patients
2.2. Control Group
2.3. Effects on Pain
2.4. Effect on Quality of Life and Mood Symptoms
2.5. Safety
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Inclusion and Exclusion Criteria
- Patients of both sexes over 18 years old;
- Patients with second- or third-degree OA, according to the Kellgren–Lawrence classification of a weight-bearing radiograph of the knee taken no more than one year ago;
- Patients with VAS (Visual Analogue Scale) > 5/10 refractory to systemic drug therapy;
- Patients who understood the study’s objectives and were able to provide their written informed consent to participate in the study and to use their data anonymously for scientific purposes.
- Age < 18 years old;
- Presence of an active malignancy of any type or history of malignancy;
- Grade I arthritis according to the Kellgren–Lawrence criteria;
- Local or systemic infection;
- Uncooperative patients, those suffering from neurological disorders and who were therefore unable to follow the physician’s instructions or unable to provide informed consent for participation in the study, or those who did not provide written consent;
- Any cases not described in the inclusion criteria.
4.3. End Points
- a statistically significant difference (p < 0.05) in functional mobility and walking ability (six-minute walking test) between T3 and T0 and between T4/T5 and T0.
- a statistically significant difference (p < 0.05) in general health assessment (SF-36) between T3 and T0 and between T4/T5 and T0.
- a statistically significant difference (p < 0.05) in mood disorders (Zung SAS and Zung SDS) between T3 and T0 and between T4/T5 and T0.
4.4. Safety Endpoints
4.5. Experimental Protocol
4.6. Questionnaires
4.7. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Hyalubrix 30 mg/2 mL (n = 35) | DIART 1.8%/2 mL (n = 35) | |
---|---|---|
Females | 20 (57.1) | 18 (51.4) |
Males | 15 (42.9) | 17 (48.6) |
BMI | 25.91 ± 2.73 | 25.86 ± 2.38 |
Age | 58.71 ± 12.15 | 57.91 ± 7.97 |
Knee OA (site) | ||
Left | 15 (42.9) | 16 (45.7) |
Right | 20 (57.1) | 15 (42.9) |
Bilateral | 0 | 4 (11.4) |
Kellgren–Lawrence grade | ||
II | 6 (17.1) | 4 (11.4) |
III | 22 (62.9) | 22 (62.9) |
IV | 7 (20.0) | 9 (25.7) |
Comorbidities | ||
Hypertension | 9 (25.7) | 20 (57.1) * |
Dysthyroidism | 9 (25.7) | 9 (25.7) |
Diabetes Type 2 | 0 | 7 (20.0) * |
Osteoporosis | 16 (45.7) | 9 (25.7) |
Fibromyalgia | 3 (8.6) | 0 |
Neurologic disease | 2 (5.7) | 1 (2.9) |
Orthopedic disease | 1 (2.9) | 1 (2.9) |
Anxiety/depression | 4 (11.4) | 2 (5.7) |
Nephro-urologic disease | 3 (8.6) | 0 |
Gastroenterological disease | 6 (17.1) | 6 (17.1) |
Dyslipidemia | 3 (8.6) | 10 (28.6) * |
Rheumatological disease | 0 | 3 (8.6) |
Hyalubrix 30 mg/2 mL (n = 35) | DIART 1.8%/2 mL (n = 35) | |
---|---|---|
NSAIDs | 13 (37.1) ** | 6 (17.1) |
Opioids | 2 (5.7) | 3 (8.6) ** |
Corticosteroids | 5 (14.3) ** | 2 (5.7) |
Acetaminophen | 1 (2.9) | 3 (8.6) ** |
Man | Women | |
---|---|---|
Number (%) | 32 (64.0) ** | 18 (36.0) |
Age | 46.38 ± 12.27 | 47.59 ± 11.93 |
Body mass index (kg/m2) | 26.40 ± 1.98 | 25.55 ± 1.79 |
Mean symptom duration (years) | 4.59 ± 3.76 years | 5.86 ± 4.12 years ** |
Osteoarthritis; Kellgren–Lawrence classification | n (%) | n (%) |
Stage I | 6 (18.8) | 4 (22.2) |
Stage II | 25 (78.1) | 13 (72.2) |
Stage II/III | 1 (3.1) | 1 (5.6) |
Stage III | 0 | 0 |
Score | T0 | T1 | PT1 vs. T0 | T2 | P T2 vs. T0 | T3 | P T3 vs. T0 |
---|---|---|---|---|---|---|---|
Visual Analogue Scale | |||||||
Hyalubrix | 7.69 ± 0.90 | 4.20 ± 0.63 | 0.000 ** | 1.57 ± 0.50 | 0.000 ** | 0.29 ± 0.46 | 0.000 ** |
DIART | 7.89 ± 0.90 | 3.89 ± 0.76 | 0.000 ** | 1.77 ± 0.60 | 0.000 ** | 0.20 ± 0.47 | 0.000 ** |
KOOS | |||||||
Hyalubrix | 47.34 ± 14.31 | 50.91 ± 15.17 | 0.000 ** | 56.97 ± 14.83 | 0.000 ** | 67.26 ± 10.32 | 0.000 ** |
DIART | 49.49 ± 15.68 | 53.97 ± 16.82 | 0.000 ** | 61.00 ± 15.82 | 0.000 ** | 70.60 ± 12.18 | 0.000 ** |
Six-minute walking test | |||||||
Hyalubrix | 336.20 ± 78.53 | 363.46 ± 81.93 | 0.000 ** | 396.10 ± 82.65 | 0.000 ** | 435.03 ± 77.83 | 0.000 ** |
DIART | 348.77 ± 100.36 | 368.11 ± 101.43 | 0.000 ** | 401.77 ± 100.58 | 0.000 ** | 444.46 ± 95.60 | 0.000 ** |
Walking test visual analogue scale | |||||||
Hyalubrix | 7.46 ± 1.38 | 7.26 ± 1.22 | 0.000 ** | 5.26 ± 1.27 | 0.000 ** | 1.94 ± 1.19 | 0.000 ** |
DIART | 7.49± 1.46 | 7.31 ± 1.35 | 0.012 ** | 5.34 ± 1.33 | 0.000 ** | 1.74 ± 1.09 | 0.000 ** |
Timed up and go test (sec) | |||||||
Hyalubrix | 9.37 ± 2.18 | 8.94 ± 2.13 | 0.000 ** | 8.34 ± 1.71 | 0.000 ** | 7.29 ± 1.15 | 0.000 ** |
DIART | 9.17 ± 2.42 | 8.80 ± 2.55 | 0.026 ** | 8.34 ± 2.25 | 0.000 ** | 7.14 ± 1.59 | 0.000 ** |
Score | T0 | T4 | PT4 vs. T0 | T5 | P T5 vs. T0 |
---|---|---|---|---|---|
Visual analogue scale | |||||
Hyalubrix 30 mg/2 mL | 7.69 ± 0.90 | 0.80 ± 0.72 | 0.000 ** | 7.46 ± 0.66 | 0.073 |
DIART 1.8%/2 mL | 7.89 ± 0.90 | 0.80 ± 1.08 | 0.000 ** | 6.83 ± 1.42 | 0.000 ** |
Knee Injury and Osteoarthritis Outcome score | |||||
Hyalubrix 30 mg/2 mL | 47.34 ± 14.31 | 78.71 ± 10.10 | 0.000 ** | 74.71 ± 10.38 | 0.000 ** |
DIART 1.8%/2 mL | 49.49 ± 15.68 | 79.54 ± 13.83 | 0.000 ** | 75.63 ± 13.15 | 0.000 ** |
Six-minute walking test | |||||
Hyalubrix | 336.20 ± 78.53 | 439.26 ± 78.05 | 0.000 ** | 416.29 ± 77.86 | 0.000 ** |
DIART 1.8%/2 mL | 348.77 ± 100.36 | 448.46 ± 95.99 | 0.000 ** | 435.74 ± 94.97 | 0.000 ** |
Walking test visual analogue scale | |||||
Hyalubrix 30 mg/2 mL | 7.46 ± 1.38 | 0.86 ± 1.19 | 0.000 ** | 3.57 ± 1.98 | 0.000 ** |
DIART 1.8%/2 mL | 7.49 ± 1.46 | 0.60 ± 0.85 | 0.000 ** | 3.34 ± 1.43 | 0.000 ** |
Timed up and go test (sec) | |||||
Hyalubrix 30 mg/2 mL | 9.37 ± 2.18 | 7.06 ± 1.00 | 0.000 ** | 8.26 ± 1.34 | 0.004 ** |
DIART 1.8%/2 mL | 9.17 ± 2.42 | 6.77 ± 1.21 | 0.000 ** | 8.26 ± 1.50 | 0.017 ** |
Score | T0 | T3 | p |
---|---|---|---|
KOOS | 46.35 ± 18.36 | 49.58 ± 15.21 | 0.340 |
VAS | 6.78 ± 1.35 | 7.1 ± 2.18 | 0.379 |
Six-minute walking test (meters) | 450 ± 126 | 461 ± 115 | 0.649 |
Walking test VAS | 7.52 ± 1.25 | 6.98 ± 2.16 | 0.223 |
Timed up and go test (sec) | 7.6 ± 2.3 | 5.51 ± 1.98 | 0.209 |
SF-36 | ||||||
---|---|---|---|---|---|---|
Hyalubrix 30 mg/2 mL | p | DIART 1.8%/2 mL | p | |||
T0 | T3 | T0 | T3 | |||
Physical functioning | 38.38 ± 15.31 | 51.29 ± 7.31 | 0.000 ** | 42.43 ± 14.06 | 54.00 ± 8.72 | 0.000 ** |
Role limitations due to physical health | 46.32 ± 23.14 | 72.86 ± 18.56 | 0.000 ** | 47.90 ± 22.99 | 73.57 ± 17.09 | 0.000 ** |
Role limitations due to emotional problems | 40.94 ± 25.69 | 59.05 ± 25.69 | 0.000 ** | 41.89 ± 23.37 | 65.73 ± 22.13 | 0.000 ** |
Energy/fatigue | 44.86 ± 13.58 | 55.14 ± 13.20 | 0.000 ** | 49.29 ± 10.86 | 59.57 ± 11.66 | 0.000 ** |
Emotional well-being | 45.83 ± 10.15 | 53.14 ± 10.16 | 0.000 ** | 48.57 ± 11.36 | 59.54 ± 12.19 | 0.000 ** |
Social functioning | 52.14 ± 13.38 | 61.43 ± 15.27 | 0.000 ** | 48.36 ± 16.46 | 58.93 ± 16.76 | 0.000 ** |
Pain | 50.71 ± 10.28 | 59.21 ± 9.39 | 0.001 ** | 55.64 ± 12.75 | 68.80 ± 12.21 | 0.000 ** |
General health | 50.57 ± 13.71 | 60.71 ± 13.73 | 0.000 ** | 46.86 ± 13.18 | 57.00 ± 13.46 | 0.000 ** |
Health change | 44.29 ± 16.14 | 60.71 ± 17.45 | 0.000 ** | 45.86 ± 18.53 | 64.43 ± 15.09 | 0.000 ** |
Zung’s scales | ||||||
Depression | 60.83 ± 6.61 | 52.60 ± 7.23 | 0.000 ** | 61.86 ± 11.33 | 53.97 ± 10.80 | 0.000 ** |
Anxiety | 60.77 ± 7.71 | 52.20 ± 8.40 | 0.000 ** | 58.51 ± 10.15 | 51.83 ± 9.55 | 0.000 ** |
SF-36 | ||||||
---|---|---|---|---|---|---|
Hyalubrix 30 mg/2 mL | p | DIART 1.8%/2 mL | p | |||
T0 | T4 | T0 | T4 | |||
Physical functioning | 38.38 ± 15.31 | 57.14 ± 7.10 | 0.000 ** | 42.43 ± 14.06 | 59.71 ± 8.22 | 0.000 ** |
Role limitations due to physical health | 46.32 ± 23.14 | 68.57 ± 20.42 | 0.015 ** | 47.90 ± 22.99 | 70.00 ± 18.98 | 0.000 ** |
Role limitations due to emotional problems | 40.94 ± 25.69 | 78.11 ±21.30 | 0.000 ** | 41.89 ± 23.37 | 80.97 ± 18.56 | 0.000 ** |
Energy/fatigue | 44.86 ± 13.58 | 60.14 ± 13.20 | 0.000 ** | 49.29 ± 10.86 | 64.57 ± 11.66 | 0.000 ** |
Emotional well-being | 45.83 ± 10.15 | 61.14 ± 10.16 | 0.000 ** | 48.57 ± 11.36 | 67.54 ± 12.19 | 0.000 ** |
Social functioning | 52.14 ± 13.38 | 70.71 ± 12.84 | 0.000 ** | 48.36 ± 16.46 | 71.07 ± 17.09 | 0.000 ** |
Pain | 50.71 ± 10.28 | 63.36± 9.66 | 0.002 ** | 55.64 ± 12.75 | 74.29 ± 12.12 | 0.000 ** |
General health | 50.57 ± 13.71 | 70.71± 13.73 | 0.000 ** | 46.86 ± 13.18 | 67.00 ± 13.46 | 0.000 ** |
Health change | 44.29 ± 16.14 | 78.57 ± 15.03 | 0.001 ** | 45.86 ± 18.53 | 83.57 ± 13.48 | 0.000 ** |
Zung’s scales | ||||||
Depression | 60.83 ± 6.61 | 55.91 ±7.22 | 0.000 ** | 61.86 ± 11.33 | 56.60 ± 10.70 | 0.000 ** |
Anxiety | 60.77 ± 7.71 | 55.400 ± 8.35 | 0.000 ** | 58.51 ± 10.15 | 56.37 ± 9.65 | 0.009 ** |
SF-36 | ||||||
---|---|---|---|---|---|---|
Hyalubrix 30 mg/2 mL | p | DIART 1.8%/2 mL | p | |||
T0 | T5 | T0 | T5 | |||
Physical functioning | 38.38 ± 15.31 | 53.86 ± 9.24 | 0.000 ** | 42.43 ± 14.06 | 54,00 ± 9.46 | 0.000 ** |
Role limitations due to physical health | 46.32 ± 23.14 | 57.86 ± 19.90 | 0.000 ** | 47.90 ± 22.99 | 55.71 ± 19.26 | 0.078 |
Role limitations due to emotional problems | 40.94 ± 25.69 | 69.54 ± 21.96 | 0.000 ** | 41.89 ± 23.37 | 68.58 ± 24.19 | 0.000 ** |
Energy/fatigue | 44.86 ± 13.58 | 50.29 ±14.85 | 0.001 ** | 49.29 ± 10.86 | 57.43 ± 11.91 | 0.000 ** |
Emotional well-being | 45.83 ± 10.15 | 57.14 ± 10.16 | 0.000 ** | 48.57 ± 11.36 | 63.54 ± 12.19 | 0.000 ** |
Social functioning | 52.14 ± 13.38 | 56.07 ± 12.27 | 0.086 | 48.36 ± 16.46 | 55.00 ± 14.28 | 0.005 ** |
Pain | 50.71 ± 10.28 | 53.36 ± 9.66 | 0.002 ** | 55.64 ± 12.75 | 64.29 ± 12.12 | 0.000 ** |
General health | 50.57 ± 13.71 | 55.71 ± 13.73 | 0.000 ** | 46.86 ± 13.18 | 52.00 ± 13.46 | 0.000 ** |
Health change | 44.29 ± 16.14 | 28.571 ± 15.03 | 0.001 ** | 45.86 ± 18.53 | 33.57 ± 13.48 | 0.000 ** |
Zung’s scales | ||||||
Depression | 60.83 ± 6.61 | 59.74 ± 6.64 | 0.000 ** | 61.86 ± 11.33 | 62.71 ± 14.09 | 0.626 |
Anxiety | 60.77 ± 7.71 | 59.63 ± 8.00 | 0.000 ** | 58.51 ± 10.15 | 52.34 ± 15.27 | 0.002 ** |
SF-36 | |||
---|---|---|---|
T0 | T3 | p | |
Physical functioning | 51.35 ± 10.22 | 52.51 ± 10.16 | 0.570 |
Role limitations due to physical health | 57.63 ± 12.65 | 56.95 ± 9.21 | 0.759 |
Role limitations due to emotional problems | 50.26 ± 9.25 | 51.62 ± 8.81 | 0.453 |
Energy/fatigue | 54.51 ± 8.43 | 56.15 ± 12.23 | 0.436 |
Emotional well-being | 61.40 ± 8.56 | 62.26 ± 7.61 | 0.596 |
Social functioning | 59.15 ± 8.85 | 60.41 ± 11.24 | 0.534 |
Pain | 50.15 ± 10.27 | 49.12 ± 7.43 | 0.566 |
General health | 47.56 ± 12.89 | 48.56 ± 10.12 | 0.667 |
Health change | 52.10 ± 9.54 | 51.49 ± 7.55 | 0.354 |
Zung’s scales | |||
T0 | T3 | p | |
Depression | 63.51 ± 7.36 | 62.50 ± 7.91 | 0.523 |
Anxiety | 55.23 ± 9.22 | 54.76 ± 9.14 | 0.798 |
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Rania, V.; Vocca, C.; Marcianò, G.; Caroleo, M.C.; Muraca, L.; Toraldo, E.; Greco, F.; Palleria, C.; Emerenziani, G.P.; Gallelli, L. Comparative Efficacy and Safety of Two Different Formulations of Linear Hyaluronic Acid in Patients with Knee Osteoarthritis. Pharmaceuticals 2025, 18, 1065. https://doi.org/10.3390/ph18071065
Rania V, Vocca C, Marcianò G, Caroleo MC, Muraca L, Toraldo E, Greco F, Palleria C, Emerenziani GP, Gallelli L. Comparative Efficacy and Safety of Two Different Formulations of Linear Hyaluronic Acid in Patients with Knee Osteoarthritis. Pharmaceuticals. 2025; 18(7):1065. https://doi.org/10.3390/ph18071065
Chicago/Turabian StyleRania, Vincenzo, Cristina Vocca, Gianmarco Marcianò, Maria Cristina Caroleo, Lucia Muraca, Emanuele Toraldo, Francesca Greco, Caterina Palleria, Gian Pietro Emerenziani, and Luca Gallelli. 2025. "Comparative Efficacy and Safety of Two Different Formulations of Linear Hyaluronic Acid in Patients with Knee Osteoarthritis" Pharmaceuticals 18, no. 7: 1065. https://doi.org/10.3390/ph18071065
APA StyleRania, V., Vocca, C., Marcianò, G., Caroleo, M. C., Muraca, L., Toraldo, E., Greco, F., Palleria, C., Emerenziani, G. P., & Gallelli, L. (2025). Comparative Efficacy and Safety of Two Different Formulations of Linear Hyaluronic Acid in Patients with Knee Osteoarthritis. Pharmaceuticals, 18(7), 1065. https://doi.org/10.3390/ph18071065