Think of IRAP treatment as the defensive line in the war against equine degenerative joint diseases.

“IRAP” may sound like the vanity plate off of a groom’s hatchback or hip-hop mogul’s Bentley, but it actually stands for interleukin-1 receptor antagonist protein (IL-1Ra) and is one of the newest developments in the treatment of equine osteoarthritis.

Osteoarthritis, also known as OA, affects the horse’s musculoskeletal system and specifically the joints, where two or more bones meet. Arthritis-related joint problems include pain, stiffness, inflammation and damage to joint cartilage (the tough, smooth tissue that covers the ends of the bones, enabling them to glide against one another) and surrounding structures.

Such damage can lead to joint weakness, instability and visible deformities that, depending on the location of joint involved can, at best, interfere with the horse’s performance and, at worst, can affect his quality of life.

IRAP, which is naturally present in the body, helps to prevent OA. But when IRAP is in low supply, OA can take hold and do a number on your horse’s joints. IRAP therapy aims to increase the amount of this protein in the horse so that his body can naturally fight OA.

Technically speaking, IRAP competes with the degrading force of interleukin-1 (IL-1) for the same receptor sites in the horse’s joints; therefore, the more IRAP present in your horse’s system, the less IL-1 harms your horse.

Unlike traditional OA therapy (such as non-steroidal anti-inflammatory drugs) that treats the symptoms, IRAP therapy actually inhibits one of the disease process’ major causes.

“Most current clinical treatments have been directed toward lowering and then maintaining a decreased degree of inflammation within damaged joints and little attention has been focused on therapeutic agents that actually protect the joint tissues,” said David D. Frisbie, DVM, PhD, an assistant professor at Colorado State University, in a 2000 report on the use of gene therapy for arthritis treatment.


It Really Works
This study featured Frisbie’s work in constructing a virus that contained the equine IL-1Ra gene sequence. That virus was then injected into horses’ diseased joints, where it was able to use the horses’ own cellular machinery to manufacture IL-1Ra (IRAP).

Frisbie then evaluated this process and its resulting IRAP product for its ability to combat the effects of synovitis and OA in exercising horses.

Decreased pain (measured by degree of lameness), decreased joint fluid levels, and fewer disease-related changes to joint tissues were found in treated joints.

In a 2002 research article published in Gene Therapy, Frisbie and his colleagues presented further support for the therapeutic benefits of IRAP. “This is the first study to demonstrate a clinical improvement in OA as a result of gene therapy. Based on the significant improvements in clinical gross and histological examinations of OA joints treated with the EqIL-1Ra gene, this therapy is practical and efficient for the equine OA patient and may offer promise for human patients in the future,” they concluded.

Not all forms of IRAP therapy involve genetic manipulation. A manmade form of IRAP, anakinra, which is marketed by Amgen under the name Kineret, was approved by the U.S. Food and Drug Administration in 2001 for the treatment of rheumatoid arthritis in humans. The daily subcutaneous injections are used to decrease the pain and swelling of moderate to severe RA.

A group of German researchers has also developed a method of creating an IRAP-rich serum from a patient’s own blood, which can then be injected into diseased joints. The Düsseldorf-based company, Orthogen, developed the preparation, Orthokine, in 1997, and it’s approved for human use in Europe and Australia.

Orthokine is created by withdrawing blood from the human or equine patient into a large syringe containing specially treated glass beads, which increase the surface area inside the syringe. During a 24-hour incubation period, blood cells interact with the bead surface, which simulates a wound, to produce large quantities of IRAP and other anti-inflammatory products.

The syringes are then placed in a centrifuge to separate blood from the serum, which can then be immediately injected into a problem area or frozen for future use. A research paper describing their serum production system was published in a 2003 issue of Inflammation Research.

“Because the serum is derived from the animal’s own blood, the possibility of adverse allergic or anaphylactic side effects is drastically reduced,” according to literature from Arthrex Vet Systems, a Florida-based Orthogen distributor. “The serum produced using IRAP has been used worldwide by veterinary surgeons for over three years without negative reactions or side effects.”

A study of Orthokine’s safety and efficacy for the treatment of human back pain was released in July 2004. Dr. Cordelia Becker, of the orthopedic clinic at the Ruhr-University Bochum, Germany, found that “in comparison to cortisone therapy, the Orthokine treatment, free of side-effects, was just as effective, and furthermore lasted considerably longer.”

Results were released in May 2005 from another German trial, conducted at the Heinrich Heine University Düsseldorf, Germany, which studied the effects of Orthokine injections in the arthritic knee joints of approximately 400 people.

“The Orthokine group reported an improvement in pain intensity of more than 50 percent, while the improvement in the hyaluronic acid and placebo groups was only 25 percent,” according to Dr. Axel Baltzer, of the Center for Molecular Orthopedics, Konigsallee Clinic.

Use In The Horse
Support for similar IRAP therapy in horses is mounting. A clinical pilot study of Orthokine treatment in 20 horses was performed by Thomas Weinberger, DVM, of the Equine Clinic Burg Mueggenhausen (Germany).

“Only horses with moderate and severe cartilage erosions with a poor prognosis to come back to normal performance were taken for the study,” he reported. “Even with the poor prognosis after arthroscopy, the results showed 70 percent of the horses without lameness and back to training after the last follow-up control.”

Weinberger developed treatment guidelines for the use of Orthokine IRAP in horses based upon three years of experience with the technique in more than 900 joints. He created a chart describing dosage amounts for various applications and recommended removing as much IL-1 harboring joint effusion as possible before injecting IRAP to improve the odds in the IL-1 vs. IL-1Ra battle.

Weinberger also delineates two groups of patients best suited for IRAP treatment. The first group “has well-defined synovitis and capsulitis that has previously been treated with hyaluronic acid and/or corticosteroids with little or no improvement,” he said, noting that such cases have responded well to IRAP. “It would also appear that this group of patients is ideal for a veterinarian to select initially, as he or she can clearly evaluate the superiority of this treatment to conventional treatments.”

The second group “has post-arthroscopic joints with focal articular cartilage disease,” he continued. “A high success rate has been seen in this group in cases treated in Europe.”

Brent Hague, DVM, of Oakridge Equine Hospital, in Edmond, Okla., presented his clinical impressions of Orthokine treatment for the performance horse at the July 2005 American College of Veterinary Surgeons Diplomate Resort Meeting. Having used the therapy for approximately a year at that point, Hague reported treating 43 joints in various anatomical locations with the IRAP serum.

“The response to treatment is variable and depends on the degree of [degenerative joint disease] present at the time of therapy. Joints with primarily synovitis or mild degenerative joint disease respond the best. Exposed subchondral bone and/or extensive cartilage damage respond less favorably,” he explained. “Joints with mild to moderate degenerative joint disease that have become unresponsive to conventional therapies are good candidates for Orthokine therapy.”

In February, The Horse reported the findings of a Colorado State University study led by Frisbie that was presented at the 2005 AAEP Convention. The researchers had examined the efficacy of the autologous conditioned serum (ACS) IRAP therapy described above.

“Horses treated with ACS were observed to have significantly improved lameness in osteoarthritis joints at the end of the study weeks after the last treatment compared with placebo-treated horses,” Frisbie said.

“Horses treated with ACS averaged a lameness grade of 1.3, while horses treated with the placebo were about a grade 2.1,” wrote Chad Mendell.

“This is the first controlled study that provides positive evidence for the use of ACS in equine osteoarthritis,” Frisbie said.

As with most therapies, early diagnosis appears to be a key factor in treatment success.

“The more severe the arthritis or cartilage damage in the joint, the less effective it is, which is probably common sense. If you put it in a really ugly joint with no cartilage, it’s not going to fix everything,” said Hague. “If you use it in the right applications, where you have low-grade degenerative joint disease with inflammation in the joint, it works well.

“We’ve had some horses we were not able, with routine therapies, to get the horses sound, and with IRAP, they have become sound and stayed sound for a period of time,” he continued. “It doesn’t work on every case, but it definitely has a place in therapy of joint disease.”

After an initial release of the IRAP system to a limited number of vets in the United States, Arthrex began their main release in December of 2005, just in time for the American Association of Equine Practitioners annual convention. More than 70 U.S. practitioners have since purchased their equipment and are now able to offer the therapy.

Stacey Reap