Comparative Effectiveness and Safety of Two Hyaluronic Acid Products in Knee Osteoarthritis

Patients with knee osteoarthritis receiving intra-articular viscosupplementation with hylan G-F 20 (Synvisc) as part of routine clinical care. The treating physician selects the product independently of the research protocol. Approximately 80 participants are expected in this cohort and will be followed for six months to evaluate clinical effectiveness and safety.

Hylan G-F 20 (Synvisc) is a sterile, cross-linked hyaluronan preparation of avian origin supplied in prefilled 2 mL syringes at a concentration of 8 mg/mL. It is administered by intra-articular injection into the knee according to the approved product instructions and routine clinical practice. Treatment selection and administration are determined by the treating physician independently of the research protocol.

• Synvisc

Patients with knee osteoarthritis receiving intra-articular viscosupplementation with non-animal-derived cross-linked sodium hyaluronate (Mesoheal) as part of routine clinical care. The treating physician selects the product independently of the research protocol. Approximately 80 participants are expected in this cohort and will be followed for six months to evaluate clinical effectiveness and safety.

Mesoheal is a sterile, non-animal-derived, cross-linked sodium hyaluronate preparation supplied in a prefilled 2.5 mL syringe containing 25 mg of sodium hyaluronate. It is administered by intra-articular injection into the knee according to the product instructions and routine clinical practice. Treatment selection and administration are determined by the treating physician independently of the research protocol.

• Mesoheal

Treatment response will be defined as an improvement of at least 20% from baseline in at least two of four effectiveness measures: knee pain assessed using the Visual Analog Scale (VAS), knee-related disability assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), functional status assessed using the MSH1 scale, and articular cartilage integrity assessed by magnetic resonance imaging (MRI) T2 mapping. The outcome will be reported as the percentage of participants meeting the treatment response criteria in each cohort at six months.

Knee pain intensity will be assessed using the Visual Analog Scale (VAS), ranging from 0 (no pain) to 10 (worst imaginable pain). Higher scores indicate greater pain intensity. Changes from baseline will be evaluated at 2, 4, and 6 months after viscosupplementation.

Knee osteoarthritis symptoms will be assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The questionnaire consists of 24 items covering pain (5 items), stiffness (2 items), and physical function (17 items). Each item is scored from 0 (no symptoms) to 4 (extreme symptoms), resulting in a total score ranging from 0 to 96. Higher scores indicate greater symptom severity and functional impairment. Changes in the total WOMAC score from baseline will be evaluated at 2, 4, and 6 months after viscosupplementation.

Knee functional status will be assessed using the MSH1 scale, a clinical assessment instrument comprising 10 items that evaluate mobility, walking ability, stair climbing, chair use, knee instability, pain, range of motion, extension limitation, flexion limitation, and knee alignment. The total score ranges from 0 to 70 points, with higher scores indicating better clinical and functional status. Changes in total MSH1 scores from baseline to six months after viscosupplementation will be compared between cohorts.

Articular cartilage composition will be assessed using magnetic resonance imaging (MRI) T2 mapping with CartiGram software. T2 relaxation times, expressed in milliseconds (ms), provide quantitative information related to cartilage collagen matrix organization and water content. Changes in T2 relaxation time from baseline to six months after viscosupplementation will be evaluated and compared between cohorts. This outcome assesses structural and compositional cartilage changes independently of clinical symptom improvement.

Safety will be assessed by recording adverse events following intra-articular viscosupplementation, including local pain, swelling, redness, inflammatory reactions, allergic reactions, infections, and systemic symptoms. Adverse events will be classified by intensity (mild, moderate, or severe) and seriousness (serious or non-serious). The outcome will be reported as the number and percentage of participants experiencing at least one adverse event in each cohort, regardless of its causal relationship with the treatment.

Analgesic consumption will be assessed using patient-reported medication diaries documenting the use of pain-relieving medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), during follow-up. Changes in medication use after viscosupplementation will be evaluated and compared between the Mesoheal and Synvisc cohorts.

The incremental cost-effectiveness ratio (ICER) will be calculated from the public healthcare provider perspective over six months. Direct medical costs will include viscosupplementation products, intra-articular administration, unscheduled consultations, emergency care, adverse event management, and rescue analgesics. Effectiveness will be defined as an improvement of at least 20% from baseline in at least two of four measures: VAS, WOMAC, MSH1, and MRI T2 cartilage assessment. The ICER will be calculated as the difference in mean costs per patient divided by the difference in treatment response proportions between the Mesoheal and Synvisc cohorts. Results will be expressed in Mexican pesos (MXN) per additional treatment responder.