A randomized, double-blind study on MD-knee versus HA in patients affected by knee OA: preliminary data from the JOINT study

Umberto MassafraDep of Rheumatology, S.Pietro

Fatebenefratelli HospitalRome, Italy

chief resident: Prof A.Migliore

• Meta-analysis of Meta-analysis of 76 trials76 trials• viscosupplementation is effective in OA of the knee viscosupplementation is effective in OA of the knee

− PainPain− Function Function − Patient global assessmentPatient global assessment

• efficacy comparable with NSAIDsefficacy comparable with NSAIDs• longer duration of benefits as compared to intra-articular longer duration of benefits as compared to intra-articular

corticosteroidscorticosteroids• Good safety profileGood 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 )

RestoringProtectingStrengthening

TendonsLigamentsJoint cartilage

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

Resting Pain VAS

walkingPain VAS

D.E Ruiu

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

Morning stiffness

US evaluation of bone aedema

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 methodsStudy Design: multicentric, double-blind, randomized with active control and Study Design: multicentric, double-blind, randomized with active control and two parallel arms. 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

Study design

Enrollment and start treatment

stop treatment

weeks

months months

Study procedures basal visitEnrollment

T0

second visitFirst follow-

upT3 3 months

third visitsecond follow-upT6 6 months

Adverse events

SF-36

NSAIDs consumptionParacetamol consumption

Lequesne Index evaluationVAS evaluation

Concomitant diseases

Patient demographics data

Anamnestic and clinical evaluation

Concomitant therapy due to comorbidities

Informed consent

Experimental treatment or control treatment

Previous treatment for Knee OA

Evaluation injection site

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

1

13

9,8

0

2

4

6

8

10

12

14

HA lequesne

leq T 0

Leq T3

-25%

P < 0,00001

Results at 3 months: HA

7,9

4,5

0

1

2

3

4

5

6

7

8

1

VAS T 0

Vas T 3

-45%

P < 0,00001

Results at 3months: MD Knee

13

9,7

0

2

4

6

8

10

12

14

1

Leq TO

Leq T3

-24%

P < 0,0005

Results at 3months: MD Knee

8

6

0

1

2

3

4

5

6

7

8

1

VAS T0

VAS T3

-25%

P < 0,0003

Drop out and side effects

2 pts in HA group lack of efficacylack of efficacy

2 pts in MD group 1 joint effusion after second injection1 joint effusion due to knee trauma

No sistemic side effectsNo 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