VISKOSUPLEMEN INTRAARTIKULER PADA OSTEOARTRITIS

JOAcid injection for Osteoarthritis

OSTEOARTHRITIS
Most common joint disease in human Suffering of pain Causing disability in 2% of population in the world

Grading of knee OA
Kellgren-Lawrence
Grade I Grade II Grade III Grade IV

Treatment of OA
Non Pharmacological - Patient education & empowerment

- Physiotherapy , occupational therapy & joint protection

Pharmacological

- Painkillers : Paracetamol, opioid, NSAIDs

- Intra-articular injection : corticosteroid, Hyaluronic acid (viscosupplementation)

Surgery
- Arthroscopy, osteotomy, Arthrodesis, joint replacement

Viscosupplementation
European League Against Rheumatism (EULAR)
Recommends viscosupplementation for pain reduction and function improvement in the management of OA1

American College of Rheumatology (ACR)

Recommends viscosupplementation for patients who have not responded to nonpharmacologic therapy or simple analgesics2
1. Jordan KM, Arden NK, Doherty M, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2003;62:1145-1155. 2. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendation for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum. 2000;43:1905-1915.

Viscosupplementations
1. Rooster combs hyaluronic acid (Hyalgan)
2. Synthetic cross-linked hyaluronic acid

(Synvisc)
3. Bacterial fermentation (Nuflexa) 4. NASHATM / Non Animal Stabilized Hyaluronic Acid (Durolane)

Hyaluronic Acid
Glycosaminoglycan

Poly d-glucuronic acid-n-acetyl-d-glucosamine

Hyaluronate

Synthesis of Hyaluronic Acid

Enzyme : Hyaluronic Acid Synthase

Mechanism of action of Viscosupplementation

1. Restoration of the elastoviscous properties of synovial fluid 2. Anti-inflamatory & antinociceptive properties

Greatest advantages with HA

Ability to delay surgery

Treatment given as an out-patient setting No drug medication (no regime of medicine) It works among majority of patients HA reduces NSAIDs consumptions

* Datamonitor 2002 (interviews)

Greatest disadvantages with HA

Number of injections

Risk involved with several injections

* Datamonitor 2002 (interviews)

NASHA Technology
Combination of modern biotechnological techniques &
carefully controlled stabilisation process

NASHA Technology
Non-Animal Produced by bacterial fermentation. Elimination of: animal-related allergic reaction. risk of transfer of diseases from animals. Stabilized: Long duration single injection treatment. Minimal tissue disturbance. Patent protection until 2015.

NASHA Technology
High purity Mildest form of stabilisation : binds to receptors as effectively as unmodified HA Low degree of molecular cross-linking (<0.5% -1%) ensures biocompatibility is retained (assured safety profile) Highest molecular weight (1013) Prolonged half life (4 weeks) (Note : t Hyalgan = 13.2 hours, t Synvisc = 1.5-8.8 days)

Permits very high density of HA (high dose)

Superior viscoelasticity (superior cushioning of joint) compared to all comparators

NASHA Technology
Mildest form of stabilisation

NASHA Technology 3-dimension

Natural HA NASHA Synthetic HA

NASHA product consist of three-dimensional network of hyaluronic acid

The Durolane differences

The elastic modulus and viscous modulus as functions of frequency on log scales for Durolane , Synvisc, and Artzal, in comparison with endogenous HA from a young healthy subject, an old healthy subject, and a patient with osteoarthritis.14

Bohlin VOR Rheometer System

14. gerup B, Berg P, kermark C. Non-animal stabilised hyaluronic acid: a new formulation for the treatment of osteoarthritis. BioDrugs. In press.

Content
3 ml prefilled glass syringe Each ml contains - Stabilized hyaluronic acid 20 mg - Phys. NaCl solution, pH 7 qs.

Indications
Symptomatic treatment of mild to moderate knee or hip osteoarthritis

Contraindications
None known

Dosage & Administration

Single dose 3 ml (one syringe) per knee or hip joints Recommended needle size : 18 22 G

The single-injection advantage

Elimination comparison of Durolane, Synvisc, and Artzal4-7

Overall intra-articular exposure to HA following i of different HA preparations. tion Synvisc is a registered trademark of Genzyme Corporation. Artzal is a registered trademark of Seikagaku Corporation.
4. Synvisc (Hylan GF 20) Prescribing Information, Genzyme Corp., Cambridge, MA. Available at: www.synvisc.com. Accessed February 15, 2005. 5. Brown TJ, Laurent UN, Frazer JR. Turnover of hyaluronan in synovial joints: elimination of labeled hyaluronan from the knee joint of the rabbit. Exp Physiol. 1991;76:125-134. 6. Lindenhayn K, Heilmann HH, Niederhausen T, et al. Elimination of tritium-labelled hyaluronic acid from normal and osteoarthritic rabbit knee joints. Eur J Clin Chem Clin Biochem. 1997;35:355-363. 7. Lindqvist U, Tolmachev V, Kairemo K, strm G, Jonsson E, Lundqvist H. Elimination of stabilised hyaluronan from the knee joint in healthy men. Clin Pharmacokinet. 2002;41:603-613.

Warnings
Durolane should not be injected :
If the joints is infected or severely inflammed If there is an active skin disease or infection present at or near the injection site Intravascularly or extra-articularly or in the synovial tissues or capsule

Adverse events
Transient pain
Swelling Stiffness

In OA of the knee:
restoring flexibility

kermark C, Adalberth T, Ericster J, Isacsson J. Patient-perceived efficacy of non-animal stabilized hyaluronic acid in the treatment of osteoarthritis of the knee. Poster presented at OARSI 2004.

In OA of the knee:
an advantage for patients
Patient response after a 15 single injection of Durolane Patients responding after a 13 single injection of Durolane

13. kermark C, Berg P, Bjrkman A, Malm P. Non-animal stabilized hyaluronic acid in the treatment of osteoarthritis of the kneea tolerability study. Clin Drug Invest. 2002;22:157-166. 15. Altman RD, Moskowitz RW, Group atHS. Intra-articular hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial. J Rheumatol. 1998;25:2203-2212.

In OA of the knee:
Percent response rate (WOMAC pain score)
*

* P < 0.05

NASHA
Placebo

WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index

Altman RD, Akermark C, Beaulieu,etal. Effficacy and safety of a single intraarticular injection of non-animal stabilized hyaluronic acid (NASHA) in patients With osteoarthritis of the knee. Osteoarthritis Cartilage 2004; 12:624-9

In OA of the hip:
Improvement in WOMAC scores
8

the new flexible advantage

Patient assessment of 8 global status

8. Berg P, Olsson U. Intra-articular injection of non-animal stabilised hyaluronic acid (NASHA) for osteoarthritis of the hip: a pilot study. Clin Exp Rheumatol. 2004;22:300-306.

One flexible advantage

Restores mobility and flexibility to the knee and hip with the convenience of a single injection Cushions the blow of OA with proven pain relief and patient satisfaction Superior physiochemical properties compared to other HA preparations Well tolerated and safe
Longer half life : one injection / 6 months Non animal origin ( allergic reaction, risk of transfer of diseases from Animal )

NASHA -based products have benefited patients throughout the world in numerous indications
Durolane is a registered trademark and NASHA is a trademark owned by Q-Med AB. All content 2005, Q-Med AB.

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