Large Joints Feature

The American Academy of Orthopaedic Surgeons (AAOS) is recommending two revised clinical practice guidelines (CPG) for treatment of osteoarthritis of the knee. One is a reduction from 4, 000 mg of acetaminophen to 3, 000 mg a day, based on a change made by the FDA in 2009 for any individuals—not necessarily just those with osteoarthritis—who use the drug. The second change is the withdrawal of a recommendation for the use of intra-articular hyaluronic acid as a method of treatment for patients with osteoarthritis of the knee. Previous guidelines were inconclusive regarding this treatment.

"Fourteen studies assessed intra-articular hyaluronic acid injections, " said David S. Jevsevar, M.D., MBA, chair of the Committee on Evidence-Based Quality and Value which oversees the development of clinical practice guidelines. "Although a few individual studies found statistically significant treatment effects, when combined together in a meta-analysis the evidence did not meet the minimum clinically important improvement thresholds."

The guidelines, according to the news release, are not meant to be stand alone documents but as points of reference and an educational tool for physicians and orthopaedic surgeons. Other recommendations that remain in the revised guideline include:

• Patients who only display symptoms of osteoarthritis and no other problems, such as loose bodies or meniscus tears, should not be treated with arthroscopic lavage.
• Patients with a body mass index greater than 25 should lose a minimum of 5% of their body weight.
• Patients should begin or increase their participation in low-impact aerobic exercise.
• The AAOS work group suggests that patients with symptomatic OA of the knee receive one of the following analgesics for pain:
  • Acetaminophen (not to exceed 3, 000 mg per day)
  • Intra-articular corticosteroids
  • Non-steroidal anti inflammatory drugs
• Treatments that the AAOS Work Group does not recommend are:
  • Custom made lateral wedge insoles
  • Glucosamine and/or chondroitin sulfate or hydrochloride
  • Needle lavage (aspiration of the joint with injection of saline)

Although acupuncture continues to grow in popularity, the work group found that evidence did not support its use in patients with OA of the knee.

Bioventus LLC scored a rare orthopedic FDA Premarket Approval (PMA) on August 29, 2017, for its single-injection hyaluronic acid (HA) joint lubrication product Durolane.

Over 20 million Americans suffer pain from knee osteoarthritis (OA). But, said company CEO Tony Bihl, the associated pain can be managed. Durolane has been a "proven knee OA pain reliever for more than 15 years, improving the lives of more than one million people worldwide."

PMA are big deals because companies prefer to go through the cheaper, faster and less complicated 510(k) process where the company only has to show that a "predicate device" exists in previous approvals. The PMA process is saved for truly unique devices and treatments, with very expensive clinical trials and years of data gathering to prove safety and effectiveness.

So, what makes Durolane so unique without a predicate?

Originality.

Knee osteoarthritis involves the breakdown, or degeneration, of cartilage and the synovial fluid that cushions and lubricates knee joint tissues. The company says Durolane is the original single-injection joint-fluid treatment which contains high levels of non-animal stabilized hyaluronic acid (NASHA®) technology. Hyaluronic acid is a naturally occurring molecule that provides the lubrication and cushioning in a normal joint. It is injected into indicated joints

The company says the product is the only HA treatment for OA that is based on NASHA. That technology is the component of several medical products that use this unique HA and its properties to provide healthcare solutions.

The technology has an advanced patented process of HA. It is a highly purified product produced without using any animal-sourced materials, ensuring that the risk of impurities is close to zero. The product is treated by the body in the same way as the body’s own hyaluronic acid and there have been no reported cases or instances of immunological or anaphylactic reactions.

The original clinical development of Durolane was founded upon three randomized, controlled trials. The initial two trials were superiority studies versus saline; the third was a non-inferiority trial versus the commonly used corticosteroid, methylprednisolone acetate.

Benefits

According to the company, the potential benefits of Durolane include:

• Directly treats the affected joint
• Treatment is repeatable as required by your physician
• May help to avoid or delay hip or knee replacement surgery
• Long-term freedom from osteoarthritis pain
• Simple & quick to administer
• Drug-free alternative to pills

Indications

In the U.S., symptomatic treatment of mild to moderate knee osteoarthritis.

Ready to use intra-articular hyaluronic acid (HA) injections for patients with knee osteoarthritis (OA)? Hold on, says new research from The University of Arkansas for Medical Sciences (UAMS).

Their work, “Comparative Effectiveness of Intra-Articular Hyaluronic Acid and Corticosteroid Injections on the Time to Surgical Knee Procedures,” appears in the December 2017 edition of The Journal of Arthroplasty.

The authors wrote, “A nested cohort of persons with knee OA [osteoarthritis] seeing a specialist was created using a 10% random sample of LifeLink Plus claims (2010-2015) to compare the risk of composite (any) knee surgical interventions, total (TKA [total knee arthroplasty]/unicompartmental knee arthroplasty (UKA) and TKA only among HA users and 2 comparison groups: corticosteroid (CS) users and HA/CS nonusers.”

“Among 13,849 patients, 797 were HA users, 5,327 were CS users, and 7,725 were HA/CS nonusers…the risk of composite surgical interventions did not differ between HA users and HA/CS nonusers.”

C. Lowry Barnes, M.D., chair of the University of Arkansas for Medical Sciences (UAMS) College of Medicine’s Department of Orthopaedic Surgery and co-author on the study, told OTW, “Like many institutions, ours has a real interest in big data. Use of databases such as LifeLink Plus allow us to study interventions and how they affect a large numbers of individuals over a period of time.”

“This study has not changed my practice as the data did not suggest a significant enough benefit of HA for me to begin providing these to patients with knee osteoarthritis. Certainly, we must take a host of factors and data into consideration as we make individual decisions about our patients, but large database studies such as this can help add to our knowledge regarding specific interventions.”

Anika Therapeutics, Inc., following up on the success of its CINGAL 13-01 trial for knee osteoarthritis (OA), is announcing that CINGAL 13-02 has also been a home run. The study evaluated the safety of a repeat injection of CINGAL for symptomatic relief of knee OA. According to Anika Therapeutics, CINGAL is made up of its proprietary cross-linked sodium hyaluronate (MONOVISC) with an FDA-approved steroid, triamcinolone hexacetonide.

“CINGAL is poised to be the first injectable viscosupplement that combines the proven benefits of our proprietary hyaluronic acid formulation with a well-established steroid to effectively treat the symptoms associated with osteoarthritis of the knee, ” said company President and Chief Executive Officer Dr. Charles H. Sherwood in the July 9, 2015 news release. “The results of this follow-up study combined with our initial Phase 3 data suggest that CINGAL maintains a consistently strong safety profile in both an initial injection as well as a repeat injection.”

For this study, the company enrolled 242 patients who had been involved in the CINGAL 13-01 study. The CINGAL 13-02 study participants received an open-label injection of CINGAL. The team found that 6.2% of patients had an adverse event related to the study injection.

“Observed AEs [adverse events] were typical of those associated with viscosupplements (arthralgia, injection site pain, swelling, and erythema), and over 95% were considered ‘mild' or ‘moderate' in severity. All AEs were transitory, resolving naturally without treatment. The AE rate associated with CINGAL was found to be consistent across both first-time and repeat injection studies. There were no statistically significant differences between the AE profile of participants in the CINGAL 13-01 study (single injection) and those in the CINGAL 13-02 study (repeat injection).”

A company representative told OTW, “There are several aspects about CINGAL and this particular study that orthopedic surgeons will find interesting. First of all, a strong outcome from the pivotal study announced earlier this year, combined with the good retreatment safety results in this study demonstrate the efficacy of CINGAL, and suggest that CINGAL maintains a consistently strong safety profile whether it’s given as an initial injection or as a repeat injection.

Monovisc, a single injection supplement to synovial fluid of an osteoarthritic joint, and made by Anika Therapeutics, Inc., has received approval of its FDA premarket application (PMA).

The company announcement on February 25, 2014, said the product will be marketed in the U.S. by DePuy Synthes, Mitek Sport Medicine, under a licensing agreement. Anika will receive a milestone payment of $5 million when the first commercial sale is made. There will be more potential payments contingent on achieving certain performance and sales thresholds.

Monovisc is used to treat pain and improve joint mobility in patients suffering from osteoarthritis of the knee. The product, according to the company, is the first FDA approved single injection product with hyaluronic acid (HA) from a non-animal source. It is comprised of a sterile, clear, biocompatible, resorbable, viscoelastic fluid composed of partially cross-linked sodium hyaluronate (NaHA) in phosphate buffered saline.

Anika has marketed Monovisc internationally since 2008. The product is currently sold in a variety of territories, including Canada, the UK and several countries in the Middle East, Europe and Asia.

"The U.S. market for viscosupplementation therapy is experiencing double digit growth annually, " said Anika President and CEO Charles H. Sherwood, Ph.D. "We are moving forward rapidly with Mitek Sports Medicine to capitalize on the strengths of our viscosupplementation portfolio." He added that the commercial introduction of the product in the U.S. is planned to take place in conjunction with the annual meeting of the American Academy of Orthopedic Surgeons to be held in New Orleans, March 11 to 15, 2014.

Product Summary

Monovisc, according to the company, is indicated for the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative non-pharmacologic therapy and to simple analgesics (e.g. acetaminophen). It is a sterile, non-pyrogenic, viscoelastic solution of hyaluronan contained in a single-use syringe. The product consists of high molecular weight, ultra-pure natural hyaluronan, a complex sugar of the glycosaminoglycan family. The hyaluronan is derived from bacterial cells and is cross-linked with a proprietary cross-linker. The product was designed to deliver a comparable HA dose to Anika's three-injection viscosupplement, Orthovisc, in a single 4 mL intra-articular injection.