On the Front Lines of Osteoarthritis Knee Pain PFS Statement was incorrect- it was reworded Physical Therapists On the Front Lines of Osteoarthritis Knee Pain

The Growing Knee OA Population Nearly 1 in 2 adults are at risk for developing OA of the knee1 References: 1. Murphy L et al. Arthritis Rheum. 2008;59(9):1207-1213.

Helping Patients Understand OA and Its Effects Kellgren-Lawrence Radiographic Criteria for Assessment1 References: 1. Kellgren Lawrence 1957 - OA Radiology.pdf, p. 500, Figure 8 GRADE 0 GRADE 1 GRADE 2 GRADE 3 GRADE 4

The Importance of an Individualized Approach Every patient is different: Many have concomitant conditions requiring additional therapies Viable treatment choices are crucial The goal is the same: Relieve pain and slow disease progression Preserve functional independence and delay TKR

The Multimodal Approach1 Need new graphic References: 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(12):1145-1155. doi:10.1136/ard.2003.011742.

What Is Viscosupplementation? Nonsystemic therapy for OA knee pain relief1 Replaces diseased, osteoarthritic synovial fluid in the knee with hyaluronan or a derivative to reduce pain1 References: Synvisc-One Prescribing Information. Cambridge MA: Genzyme Corp; 2010

Treatment Options SYNVISC: Provides up to 6 months of OA knee pain relief with 3 injections.1 Synvisc-One: Same formulation, provides up to 6 months of OA knee pain relief with just 1 injection.2 References: 1. SYNVISC Prescribing Information, Cambridge, MA: Genzyme Corp; 2010. 2. Synvisc-One Prescribing Information. Cambridge, MA: Genzyme Corp; 2010. Single-Injection Synvisc-One® (hylan G-F 20)

Demonstrated Efficacy of SYNVISC The SYNVISC family of viscosupplements demonstrated superior OA knee pain relief versus ALL of the following in separate head-to-head clinical trials: † N=110; Primary endpoints (assessed by patients): Pain during weight-bearing, pain at rest during the night, reduction of pain during the most painful movement of the knee, and treatment success; Primary endpoints (assessed by investigator): Extent of patient’s loss of activity while performing difficult daily tasks and treatment success. Safety: There were no reports of local adverse events (AEs) to hylan G-F 20 in the injected knee. † N=253; Primary endpoint: Change from baseline over 26 weeks in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index A pain; Safety: The overall frequency of AEs were comparable between the 2 treatment groups (hylan G-F 20, n=70, 56.9%; placebo, n=79, 60.8%). The most commonly reported AEs were pain in the target knee (coded as ‘‘arthralgia’’), joint stiffness, joint effusion, and joint swelling. ‡ N=392; Primary endpoint: Inter-group difference in knee pain as measured by visual analogue scale (VAS) at 6 months; Safety: Treatment related AEs were reported in 39 patients in the hylan G-F 20 group and in 30 patients in the sodium hyaluronate group (P>0.05). § N=218; Primary endpoints: Question A1 of the WOMAC (pain while walking on a flat surface) and VAS scores for patient and investigator (blinded observer) overall assessments; Safety: No statistically significant differences were observed between treatment groups for the overall incidence of AEs or the incidence of any single AE. ¶ N=102; Comparison of efficacy of concomitant or separate treatments of hylan G-F 20 and NSAIDs; Multiple primary endpoints; Safety: AEs were reported in the case report forms of 6 patients. Three of these were unrelated to hylan G-F 20 injections. The remaining 3 patients had local and transient AEs in the injected knees. References: Wobig M, Dickhut A, Maier R, Vetter G. Viscosupplementation with Hylan G-F 20: a 26-week controlled trial of efficacy and safety in the osteoarthritic knee. Clin Ther. 1998;20(3):410-423. Chevalier X, Jerosch J, Goupille P, et al. Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial. Ann Rheum Dis. 2010;69:113-119. Raman R, Dutta A, Day N, Sharma HK, Shaw CJ, Johnson GV. Efficacy of hylan G-F 20 and sodium hyaluronate in the treatment of osteoarthritis of the knee— a prospective randomized clinical trial. Knee. 2008;15(4):318-324. Caborn D, Rush J, Lanzer W, Parenti D, Murray C. A randomized, single-blind comparison of the efficacy and tolerability of hylan G-F 20 and triamcinolone hexacetonide in patients with osteoarthritis of the knee. J Rheumatol. 2004;31(2):333-343. Adams ME, Atkinson MH, Lussier AJ, et al. The role of viscosupplementation with hylan G-F 20 (Synvisc®) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone. Osteoarthritis Cartilage. 1995;3(4):213-225. ICS = intra-articular corticosteroid; NSAID = non-steroidal anti-inflammatory drug. ||Pain at rest.

Synvisc-One® (hylan G-F 20) Indication Synvisc-One is indicated for treatment of pain in knee OA patients who have failed to respond adequately to: Conservative non-pharmacologic therapy Simple analgesics, e.g., acetaminophen Safety Profile The side effects most commonly seen in a medical study were knee pain, stiffness and swelling or fluid buildup in or around the knee Side effects were generally mild to moderate and did not last long. References: 1. Synvisc-One Prescribing Information, Cambridge, MA: Genzyme Corp; 2010

Help Patients Understand What to Expect Single 6-mL injection In-office procedure that only takes a few minutes After injection: Most patients experience relief starting one month post injection Patients should avoid strenuous or prolonged weight-bearing activities for 48 hours References: 1. Synvisc-One Prescribing Information

Part of the Multimodal Approach References: 1. Data on file. Genzyme Corp; 2009. 2. Synvisc-One Prescribing Information, Cambridge, MA: Genzyme Corp; 2010

Important Safety information Indication SYNVISC® (hylan G-F 20) and Synvisc-One® (hylan G-F 20) are indicated for the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative nonpharmacologic therapy and simple analgesics, e.g., acetaminophen. Important Safety Information SYNVISC and Synvisc-One are contraindicated in patients with known hypersensitivity to hyaluronan products or patients with infections in or around the target knee. Hypersensitivity reactions including anaphylactic reaction, anaphylactoid reaction, anaphylactic shock and angioedema have been reported for both SYNVISC and Synvisc-One. Do not concomitantly use disinfectants containing quaternary ammonium salts for skin preparation because hyaluronan can precipitate in their presence. Do not inject SYNVISC or Synvisc-One extraarticularly, into the synovial tissues, into the fat pad or joint capsule, or intravascularly. The safety and efficacy of Synvisc-One in locations other than the knee, or for conditions other than osteoarthritis, or in combination with other intra-articular injectables, or in severely inflamed knee joints have not been established. Use caution when injecting SYNVISC or Synvisc-One in patients allergic to avian proteins, feathers, or egg products; who have evidence of lymphatic or venous stasis in the leg to be treated; or who have severe inflammation in the knee to be treated. Remove any synovial fluid or effusion before injecting SYNVISC or Synvisc-One. Strict adherence to aseptic technique must be followed to avoid joint infection. The safety and effectiveness of SYNVISC and Synvisc-One have not been established in children (≤21years old) or in pregnant or lactating women. Patients should be advised to avoid strenuous or prolonged weight-bearing activities for approximately 48 hours after treatment. For SYNVISC In clinical trials, the most commonly reported adverse events were transient pain, swelling, and or joint effusion in the injected knee. The following reported adverse events are among those that may occur in association with intra-articular injections, including Synvisc: arthralgia, joint stiffness, joint effusion, joint swelling, joint warmth, injection site pain, arthritis, arthropathy, and gait disturbance. For Synvisc-One The most commonly reported adverse events were arthralgia, arthritis, arthropathy, injection site pain, and joint effusion. The following reported adverse events are among those that may occur in association with intra-articular injections, including Synvisc-One: arthralgia, joint stiffness, joint effusion, joint swelling, joint warmth, injection site pain, arthritis, arthropathy, and gait disturbance.