Federal law restricts this device to sale by or on the order of a physician (or properly licensed practitioner).
ORTHOVISC® is a sterile, non-pyrogenic, clear, viscoelastic solution of hyaluronan contained in a single-use syringe. ORTHOVISC® consists of high molecular weight (1.0-2.9 million daltons), ultra-pure natural hyaluronan dissolved in physiological saline. Hyaluronan is a natural complex sugar of the glycosaminoglycan family. The hyaluronan is extracted from chicken combs.
ORTHOVISC® is indicated in the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative nonpharmacologic therapy and to simple analgesics, e.g., acetaminophen.
ORTHOVISC® was investigated in 3 randomized, controlled clinical studies conducted in the U.S. An integrated safety analysis was conducted, pooling the ORTHOVISC® groups from the 3 studies and pooling the control groups, which were either intra-articular saline injections or arthrocentesis. In the integrated analysis, there were 562 patients in the groups treated with ORTHOVISC® (434 receiving 3 injections and 128 receiving 4 injections), 296 in the group treated with physiological saline, and 123 in the group treated with arthrocentesis.
Adverse events occurring at >5% of the overall integrated population included: arthralgia (12.6% in the ORTHOVISC® group, 17.2% in the saline group, and 0.8% in the arthrocentesis group); back pain (6.9% in the ORTHOVISC® group, 12.2% in the saline group, and 4.9% in the arthrocentesis group); and headache NOS (12.1% in the ORTHOVISC® group, 16.6% in the saline group, and 17.9% in the arthrocentesis group). Injection site adverse events (including erythema, edema, pain and reaction NOS) occurred at rates of 0.4%, 0.9%, 2.5% and 0.2%, respectively, in the ORTHOVISC® group, compared to 0.0%, 0.3%, 2.0%, and 0.7% in the saline group and 0.0%, 0.0%, 0.8% and 0.8% in the arthrocentesis group. Local adverse events reported on a by-patient basis for the combined ITT populations of the three studies are presented in Table 1.
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Additional adverse event information was obtained from an open label study (OAK0101). The objective of the open label study was to evaluate the safety of a repeat course of intra-articular ORTHOVISC®. The patients enrolled in the open label study were previously enrolled in one of the randomized studies (OAK2001). Patients who completed OAK2001 and had persistent pain in the index knee received 3 weekly injections of ORTHOVISC ® six months following the first treatment course and were followed for 6 weeks. Of 190 eligible patients, 127 had been assigned to either 4 injections of ORTHOVISC® or to 3 injections of ORTHOVISC® plus one arthrocentesis in OAK2001 and therefore underwent two courses of ORTHOVISC ® treatment between the two studies. In OAK0101, adverse event profiles (type, frequency and severity of adverse events) were comparable among the three treatment groups (those who had undergone a previous series of 3 or 4 ORTHOVISC® injections and those who received only arthrocentesis in OAK2001) and were similar to those seen in the OAK2001 study and the integrated safety analysis. Table 2 compares adverse event data for patients receiving ORTHOVISC® among the integrated safety analysis ("Single Treatment"), the OAK2001 randomized study ("Single Treatment") and the OAK0101 retreatment study ("Repeat Treatment").
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The effectiveness of ORTHOVISC® for the treatment of osteoarthritis of the knee was evaluated in three main studies; two randomized, controlled, double-blind multicenter studies (OAK9501 and OAK2001) that involved unilateral treatment, and one study (OAK9801) that involved bilateral treatment. Because bilateral treatment confounded the assessment of effectiveness of the OAK9801 study, the effectiveness data are summarized for the OAK9501 and OAK2001 studies. Safety data for all three studies are reported in "Adverse Events."
The objective of the randomized studies was to assess the effectiveness of ORTHOVISC® for the treatment of joint pain of patients with idiopathic osteoarthritis of the knee. The OAK9501 study randomized patients to 3 weekly injections of either ORTHOVISC® (O3) or saline. The OAK2001 study randomized patients to one of three treatments: 4 ORTHOVISC® injections (O4), 3 ORTHOVISC® injections + 1 arthrocentesis (O3A1) procedure, or 4 arthrocentesis (A4) procedures. Follow-up occurred at weeks 7/8, 11/12, 15/16 and 21/22, with final follow-up at week 27/28. When each study was analyzed individually, the primary analyses for each study did not show statistical significance. A combined analysis was additionally performed. The combined data consisted of data obtained from a subgroup of patients from each of the studies (the "ITT Subgroup" from OAK9501 and the "Evaluable Subgroup" from OAK2001) who had Kellgren-Lawrence radiographic grades of II or III at baseline and WOMAC pain in the contralateral knee of <175mm (out of 500) and is referred to as the effectiveness subgroup population. For the effectiveness subgroup population, the primary effectiveness analysis performed was to determine the proportion of patients achieving a 20% improvement from baseline in the WOMAC Pain Score in conjunction with a minimum absolute improvement of 50 mm from baseline in the WOMAC Pain Score, and a 40% and 50% improvement from baseline in WOMAC Pain Score at four assessment points between Weeks 7/8 to 21/22 for the index knee.
OAK9501 included 226 patients at 10 centers, and OAK2001 involved 373 patients at 24 centers. Within the individual studies, baseline and demographic variables were similar among groups. Table 3 below summarizes the baseline and patient demographic characteristics for the combined effectiveness subgroup.
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In the combined analysis of OAK9501 and OAK2001, two subgroup populations (representing patients with baseline Kellgren-Lawrence grade II or III radiographic findings and contralateral knee pain <175 mm on the WOMAC Pain Score) were analyzed together, comprising 5 treatment groups (4 ORTHOVISC® injections [O4], 3 ORTHOVISC® injections followed by 1 arthrocentesis [O3A1], 3 ORTHOVISC® injections [O3], 4 arthrocentesis procedures [A4] and 3 saline injections [Saline]). For the GEE analyses, the O3A1 and O3 groups were also pooled to form a sixth group [O3A1/O3].
The primary effectiveness analysis was performed to determine the proportion of patients achieving a 20% improvement from baseline in the WOMAC Pain Score in conjunction with a minimum absolute improvement of 50 mm from baseline in the WOMAC Pain Score, and a 40% and 50% improvement from baseline in WOMAC Pain Score at four assessment points between Weeks 7/8 to 21/22 for the index knee. A significantly larger proportion of O4 patients achieved 40% and 50% improvements from baseline in WOMAC Pain Score compared to both A4 and Saline over 7- 22 weeks (based on GEE analysis). Similarly, a significantly larger proportion of O3 and O3A1/O3 patients achieved 40% and 50% improvements from baseline in WOMAC Pain Score than Saline patients (based on GEE analysis) (Table 4). Table 5 presents the mean number of patients from the effectiveness subgroup over the four follow-up visits that achieved improvement over weeks 7 through 22.
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In summary, with respect to patients achieving >/=40% and >/=50% improvement in WOMAC Pain Score compared to baseline, the four injection ORTHOVISC ® regimen demonstrated effectiveness compared to both Saline and Arthrocentesis control procedures, and the three-weekly injection regimen demonstrated effectiveness compared to Saline in the indicated patient population.
Hyaluronan is a high molecular weight polysaccharide composed of repeating disaccharide units of sodium glucuronate and N-acetylglucosamine.
Each syringe contains the following in a 2 mL dose sterile-filled into a syringe:
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ORTHOVISC® does not contain any synthetic additives.
ORTHOVISC® is supplied as a sterile-filled solution, in a single-use syringe, sealed in a sterile pouch inside a carton. The product is presented as a sterile, non-pyrogenic solution in a 3 mL syringe. Each syringe is labeled "ORTHOVISC®" for ready identification. A rubber cap is provided on the syringe tip to prevent leakage and protect sterility of the product. The ORTHOVISC® syringe components contain no latex.
ORTHOVISC® is injected into the knee joint in a series of intra-articular injections one week apart for a total of three or four injections. Standard intraarticular injection site preparation, aseptic technique and precautions should be used. Do not concomitantly use disinfectants containing quarternary ammonium salts for skin preparation as hyaluronic acid can precipitate in their presence.
ORTHOVISC® is a registered trademark of Anika Therapeutics, Inc.
Manufactured by:Distributed by:
Anika Therapeutics, Inc. DePuy Mitek
a Johnson·Johnson company
Woburn, MA USA 01801
DePuy Mitek
325 Paramount Drive
Raynham, MA 02767
530-220 AML 06/05Product Code 59676-360-01
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ORTHOVISC® High Molecular Weight Hyaluronan
ORTHOVISC® is a viscous (thick) sterile mixture made from highly purified hyaluronan from chicken combs. Hyaluronan is a natural chemical found in the body. High amounts of hyaluronan are found in the joint tissues and in the fluid that fills the joints. The body's own hyaluronan acts like a lubricant and a shock absorber in the joint. It is needed for the joint to work properly. When you have osteoarthritis, there may not be enough natural hyaluronan in the joint, and the quality of that hyaluronan may be poorer than normal. ORTHOVISC® is given in a shot (injection) directly into the knee joint.
ORTHOVISC® is used to relieve knee pain due to osteoarthritis. It is used for patients who do not get adequate pain relief from simple pain relievers like acetaminophen or from exercise and physical therapy.
Clinical trials conducted in the U.S. have shown that ORTHOVISC® provides pain relief to patients who have not been able to find pain relief with simple pain medication or exercise compared to saline placebo injections.
If you have pain due to osteoarthritis of the knee, there are things you can do that do not involve ORTHOVISC® injections. These include:
Non-drug treatments:
Things you should know about ORTHOVISC®
Possible complications
Your healthcare professional will inject ORTHOVISC® (30 mg/2 mL) into your knee once a week, for a total of 3 or 4 injections.
Distributed by:
DePuy Mitek
a Johnson·Johnson company
DePuy Mitek
325 Paramount Drive
Raynham, MA 02767
Manufactured by:
Anika Therapeutics, Inc.
Woburn, MA 01801
530-220 AML 06/05 PI