Hyaluronic acid alone versus hyaluronic acid associated with adelmidrol for Intra-articular treatment of knee osteoarthritis: A long-term follow-up

Background: Hyaluronic acid (HA) has been used for many years for intra-articular treatment of knee osteoarthritis with satisfactory results. HA associated with Adelmidrol – an anti-neuroinflammatory compound – have been only recently introduced in orthopedic clinical practice with good preliminary results. Objective: To investigate whether HA associated with Adelmidrol provides better results than HA alone. Methods: Two cohorts of patients with moderate knee osteoarthritis were treated. Cohort 1 received 5 weekly intra-articular injections of HA during 2017 while Cohort 2, 4 weekly intra-articular injections of HA associated with Adelmidrol during 2018. The patients of the two Cohorts were assessed by WOMAC scale, SF-12 questionnaire and PGIC scale at 1 week (T0), 6 months (T1), 1 year (T2), and 2 years (T3) after the end of treatment. All the data were statistically analyzed. A p-value of <0.05 was considered statistically significant. Results: According to the WOMAC Scale Cohort 1 had higher mean scores than Cohort 2 at each follow-up time, with a statistically significant difference between the two cohorts at T3 (p<0.03) for all the WOMAC components, except for Stiffness. WOMAC Total mean score worsened statistically significantly only in Cohort 1, from T1 to T3 (T2 vs T1: p=0.0033; T3 vs T2: p=0.0007). The same happened for WOMAC Physical Function (T2 vs T1: p=0.0146; T3 vs T2: p=0.0046) and WOMAC Pain (T2 vs T1: p=0.0004; T3 vs T2: p=0.0002). WOMAC Stiffness worsened statistically significantly in Cohort 1 from T2 to T3 (T3 vs T2: p=0.0041), while in Cohort 2 no change on WOMAC scale was statistically significant at any time-point, for any components. The mean scores of the SF-12 questionnaire were better in Cohort 2 than in Cohort 1 at each follow-up time for both the Physical and the Mental components, with a statistically significant difference between the two groups for the latter, at T0 (p=0.0001). In both cohorts the mean score of the Physical component decreased from T0 to T3, but the difference was not statistically significant between the two groups (p=0.25). The mean score of the Mental component slightly increased in Cohort 1 and decreased in Cohort 2, without statistically significant differences between the two groups at any time-point. PGIC showed that Cohort 2 scored significantly better than Cohort 1 at T3 (p=0.0336). Conclusions: Overall, HA associated with Adelmidrol gave better long-term results than HA alone. KEY WORDS: Hyaluronic acid, Adelmidrol, Palmitoylethanolamide, Knee, Osteoarthritis, Synovitis, Mastocytes, Intra-articular injections, Visco-induction.