Published evidence

Suppan VKL, Tew MM, Muthusamy H, et al. (2026)

Long-term functional and clinical outcomes of intraarticular double-cross-linked high molecular weight hyaluronic acid (Crespine Gel Plus) injection in knee osteoarthritis. BMC Musculoskeletal Disorders 27:209 · DOI 10.1186/s12891-026-09588-1 · PMID 41664047

Design. Prospective single-arm cohort study, single-centre, open-label. 111 enrolled, 107 at 3 months, 92 at 12 months. Follow-up 12 months.

Result. KOOS4 rose from 62.2 to 71.0 at 12 months (+8.78; p < 0.001); pain VAS fell from 4.80 to 3.17 (−1.64; p < 0.001). The improvement appeared by month 3 and held to month 12.

Tolerability. 2 of 111 participants (1.8 %) reported transient knee pain within 24 hours, resolving within 48 hours without treatment. No septic arthritis, hypersensitivity reactions or systemic complications.

Limitations. No control or placebo arm; the authors state the design precludes causal inference. 19 of the 111 enrolled were missing at the 12-month assessment. Concomitant treatments were not recorded separately. The product studied was Crespine Gel+; any added benefit of the prilocaine was not assessed separately.

Funding. Partially funded by Nexgen Medical Sdn. Bhd., Malaysia. The authors declare no competing interests.

Shahid H, Umer M, Zahid M. (2025)

Improvement in Knee Society Score after Twelve Months of Intra-articular Viscosupplementation. Annals ASH & KMDC 29(1):17–24

Design. Prospective cohort study, Aga Khan University Hospital Karachi, Kellgren-Lawrence I–II. 25 people, 39 knees. Follow-up 12 months.

Result. Knee Society Score rose from 72.28 ± 11.18 to 81.28 ± 9.76; Knee Society Function Score from 66.79 ± 15.23 to 76.54 ± 15.39 (both p = 0.001).

Limitations. Cohort study without a control group. The planned sample of 36 was not reached; 25 people were analysed. The 39 knees come from 25 people — two knees of the same person are not statistically independent observations. Limited to mild to moderate knee osteoarthritis (Kellgren-Lawrence I–II), with baseline and one-year measurements only.

Funding. "Source of Funding: None", "Conflict Of Interest: None". The only one of the three studies with no funding from manufacturer or distributor.

Bashaireh K, et al. (2015)

Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing Phase IV study. Drug Design, Development and Therapy 9:2063–2072 · DOI 10.2147/DDDT.S81524

Design. Post-marketing Phase IV study. 109 enrolled, 84 in the full analysis set. Follow-up 9 months.

Result. 63 of 84 participants (75 %) met the OARSI criterion for 70 % responders.

Tolerability. 33 of the 84 analysed (39 %) had increased pain 72 hours after injection — 17 pain alone, 7 with redness, 5 with swelling, 4 with pain, swelling and redness. All 33 had limited knee mobility at that point. Most were treated with analgesics. All events were local and transient; no serious events occurred.

Limitations. No control group; nine-month observation period; funded by the manufacturer. The product studied was the standard variant, not Crespine Gel+.

Funding. Funded by BioPolymer GmbH & Co. KG. Protocol, data handling, statistics and the initial study report were carried out by the contract research organisation Clinical Quest. The authors declare no conflicts of interest; the corresponding author additionally declares a business relationship with the funding organisation.