A randomized, double-blind study on MD-knee versus HA in patients affected by knee OA: preliminary data from the JOINT study Umberto Massafra Dep of Rheumatology, S.Pietro Fatebenefratelli Hospital Rome, Italy chief resident: Prof A.Migliore

Meta-analysis of 76 trials viscosupplementation is effective in OA of the knee Pain Function Patient global assessment efficacy comparable with NSAIDs longer duration of benefits as compared to intra-articular corticosteroids Good safety profile

Collagen Medical Device (MD) Collagen (type I) + natural support components Swine Derivation High collagen concentration (22.8% Gly 13.8% Pro 13% Hidrox-Pro ) Restoring Protecting Strengthening Tendons Ligaments Joint cartilage

US evaluation of bone aedema Resting Pain VAS Morning stiffness D.E Ruiu walking Pain VAS US evaluation of bone aedema Rashkov R, Nestorova R, Reshkova V. Efficacy and safety of collagen injection Guna Mds in osteoarthrosis treatment of knee. IOF-ECCEO12 – March 21-24, 2012 Nestorova R, Rashkov R, Reshkova V, Kapandjieva N. Efficiency of Collagen injections “Guna MDs” in patients with gonarthrosis, assessed clinically and by US. IOF-ECCEO 12

Aim of the study to compare symptomatic effect of intra-articular treatment with MD-knee versus Sodium Hyaluronate (HA) in patients affected by knee OA

Materials and methods Study Design: multicentric, double-blind, randomized with active control and two parallel arms. Inclusion criteria: knee OA diagnosed according to ARA criteria age > 40 years disease activity ≥ 6 measured with Lequesne Knee Index (LKI) Exclusion Criteria Concomitant rheumatic diseases (RA; spondiloarthritis; connective tissue diseases; polimyalgia rheumatica; gout; Paget disease; septic arthritis; fractures; osteonecrosis and fibromyalgia) skin or soft tissue infections close to the joint to be injected oral, intravenous or intra-articular corticosteroid treatment in the previous 3 months local analgesics treatment anti-coagulant treatment; severe trombocytopoenia and/or other coagulation disorders Allergy to swine origin products

Materials and methods Two arms: Experimental Group : 2 vials (4ml) of GUNA MD-Knee Medical Device weekly for 5 consecutive weeks Control Group : 1 vial (2,5 ml) of Sodium Hyaluronate (Artz®Seikagaku, Tokyo, Japan) weekly for 5 consecutive weeks

Enrollment and start treatment Study design weeks Enrollment and start treatment months months stop treatment

Study procedures basal visit Enrollment T0 second visit First follow-up T3 3 months third visit second follow-up T6 6 months Informed consent Patient demographics data Anamnestic and clinical evaluation Concomitant diseases Lequesne Index evaluation VAS evaluation NSAIDs consumption Paracetamol consumption SF-36 Experimental treatment or control treatment Concomitant therapy due to comorbidities Previous treatment for Knee OA Evaluation injection site Adverse events

Primary endpoint Rate of LKI score decrease at 3 months

Secondary endpoints 6 month LKI variations SF 36 score at 3 and 6 months VAS variations at 3 and 6 months NSAIDs consumption and analgesics consumption at 3 and 6 months Adverse events

Statistical analysis Not inferiority evaluation t Student test for indipendent data, one code, significativity level 0.025 or U Mann-Whitney test, one code, with same level of significance for primary endpoint ANOVA test (bonferroni method) for secondary endpoints Fisher test for side effects

Results Included 60 patients: 30 in the MD-Knee arm and 30 in the HA arm females were 65% in the HA group and 64 % in the MD group mean age 69 years (range 55-84) mean Body Mass Index (BMI) 27.2 (+/-5.1) Kellgren-Lawrence radiological grades II and III almost equally represented in both study groups

Results at 3 months: HA -25% P < 0,00001

Results at 3 months: HA -45% P < 0,00001

Results at 3months: MD Knee -24% P < 0,0005

Results at 3months: MD Knee -25% P < 0,0003

Drop out and side effects 2 pts in HA group lack of efficacy lack of efficacy 2 pts in MD group 1 joint effusion after second injection 1 joint effusion due to knee trauma No sistemic side effects No infectious side effects

Conclusion Our preliminary data confirmed good symptomatic effect of MD Knee and HA to improve function and reduce pain in patients affected by symptomatic Knee OA Both treatments showed a good safety profile