PearlDiver Data Raises New Questions About Synovial Injections

Synovial injections for the treatment of osteoarthritis have been used in the United States since 1997, yet studies are still being performed to judge their efficacy. If the goal is to improve the quality of life for the patient, is that being accomplished? The latest numbers from the PearlDiver Patient Records Database cast some doubt on the effectiveness of this treatment.

Osteoarthritis is a degenerative joint disease and is the most common form of arthritis in the United States. The number of adult patients diagnosed is estimated to be over 30 million, and the numbers continue to grow as the population ages. As osteoarthritis increases within the patients’ knees, patients experience loss of cartilage. During this process, the synovial fluid within the knee changes, becoming less viscous and elastic. This decreased lubrication within the knee joint and decreased cartilage protection are the causes of pain resulting from the arthritis.

It is possible that many patients will have derived value from the perception of having delayed undergoing a total knee replacement. Each patient will have his own definition of success. Thus the value the patient sees in such a treatment will vary. If the goal is to improve the quality of life for the patient, is that being accomplished?

The current nonsurgical treatments of these symptoms include weight reduction and avoidance of activities which create excessive stress on the joint in the early stages of the disease. As the level of arthritic pain increases, the next option for a patient is typically mild pain relievers such as aspirin or acetaminophen along with anti-inflammatory medication.

However, once the pain levels become severe, the patient’s options change. In the United States, prior to 1997, the next option was arthroscopy and then a total knee replacement. The steps from aspirin and weight loss to a total knee replacement are big ones. To provide an intermediary step and to relieve patients’ severe osteoarthritic pain, synovial injections were introduced into the market.

These injections are designed to ease pain within the knee joint caused by the onset of severe osteoarthritis using hyaluronan or synthetic hylan g-f 20. Injected into the synovial membrane of the knee, the hyaluronan is supposed to supplement the synovial fluid within the osteoarthritic knee.

The demand for such a product is immense. Despite the advances in orthopedic technology and the design of knee replacements, many patients will delay undergoing a knee replacement for as long as possible, a length of time typically determined by the level of pain the patient is experiencing.

The first of these products gained FDA approval in the U.S. on May 28, 1997. Five major manufacturers now sell hyaluronan or hyaluronan derivative products in the market. These include:

• Hyalgan  (sanofi-aventis)
• Synvisc (Genzyme Corporation)
• Supartz  (Smith & Nephew)
• Orthovisc (Anika Therapeutics, Inc., Distributed by Depuy Mitek, Inc.)
• Euflexxa (Ferring Pharmaceuticals Inc.)

• Intra-articular injections of 750 kD hyaluronan in the treatment of osteoarthritis: a randomised single centre double-blind placebo-controlled trial of 91 patients demonstrating lack of efficacy, by Henderson, et al. 1994, which concluded hyaluronan injections showed no more effectiveness than the placebo given during the study.

• Viscosupplementation with hylan G-F 20: a 26-week controlled trial of efficacy and safety in the ostearthritic knee, by Wobig et al. 1998, which concluded significant effectiveness when 39% to 56% of the patients receiving hyalan injections remained pain free 10 to 24 weeks after the final injection.

• Tolerability and short-term effectiveness of hylan G-F 20 in 4253 patients with osteoarthritis of the knee in clinical practice, by Klinik Lohrey, 2005, which concluded short-term effectiveness was confirmed.

• Intra-articular sodium hayluronate 2 mL versus physiological saline 20mL versus physiological saline 2 mL for painful knee osteoarthritis: a randomized clinical trial, by Lundsgaard et al. 2008, which concluded there was no significant reduction in pain compared with the saline placebo.

These clinical trials, just a few examples of the numerous studies available, demonstrate conflicting conclusions regarding the efficacy of the injections. So how is it that in over 20 years of product use worldwide, 11 years in the U.S., study after study reveals that there is still no consensus on whether the injections are working?

Many studies reveal a snapshot of patient results. However, with help from the PearlDiver database, it is now possible to view the “whole story.” Within the PearlDiver database, 89,278 distinct patients had been diagnosed with osetarthritis as of 2004. This number increased to over 110,500 by the end of 2005. Of these patients, 9,060 were treated using synovial injections in 2004 and 12,818 were treated in 2005. With this patient data, rather than simply viewing the immediate results of the treatment, the door is open to view what happened to the patient down the road and better assess the effectiveness of the injections.

Table 1: Injections and Following Procedures

Source:  PearlDiver Patient Records Database, 2004 - June 2007

To view the “whole story” requires asking the question, “Did these patients take further action to improve their quality of their life?”

To answer this, two primary events were considered. Did the patients accept a second level of injections—indicating that their level of pain had continued or increased or did a total knee replacement follow the first series of injections? The results surprised the researchers. Out of the 9,060 patients who received a series of synovial injections in 2004, 3,255 returned for a second series of injections by June 2007, accounting for 35.9% of those patients treated with hyaluronan injections. A total of 1,585, or 17.5%, had knee replacement by that time. In total, 46.3% saw a decline in their condition significant enough to motivate them to take further action.

This took place over a 2.5 – 3.5 year time span. However the results of those patients who underwent hyaluronan injections in 2005 are just as astonishing. In total, 12,818 patients opted for the injection treatment. With the timeline remaining constant, ending in June 2007, 24.1% had already tried the injections again and 14.3% had pursued a total knee replacement. In the time frame of 1.5 – 2.5 years, 34.2% of patients had required some form of further treatment.

Viewing this in its totality, of the 21,878 patients within the PearlDiver database who received a series of hyaluronan injections for treatment of osteoarthritis, a full 39.2% had to undergo further treatment. It is also important to note, these figures do not include those patients who continued to experience pain, yet did not seek further treatment within the time frame posed. 

Looking further into the storyline, are patients getting their money’s worth from injections when such a high rate of further treatment may be required? Disregarding insurance deductibles and co-pays, the total cost of the injections is broken down in Table 2. Each injection comes with a price tag and, in addition, there is a physician charge to administer the injection. The total price tag ranges from just over $1,200 to nearly $2,000. Of the 8,753 patients within the PearlDiver database who required another procedure (a second series of injections or total knee replacement), was the cost proportionate to the outcome? 

Table 2: Cost of Injections

It is possible that many patients will have derived value from the perception of having delayed undergoing a total knee replacement. Each patient will have his own definition of success. Thus the value the patient sees in such a treatment will vary. If the goal is to improve the quality of life for the patient, is that being accomplished?