BRUSSELS – The clinical response seen to injection of a targeted, anti-inflammatory drug into an acutely damaged knee joint within a few weeks of the injury in a controlled, pilot study with 11 patients made a step toward development of a new approach to treating traumatic joint injury.
Dr. Virginia Byers Kraus
“We should start to treat joint injury much more emergently, like an acute myocardial infarction.” Acute joint injury “is a critical event where early intervention might improve long-term outcome,” including heading off the eventual development of osteoarthritis, Dr. Virginia Byers Kraus said at the meeting.
“Blocking sterile inflammation early in acute, joint injury may be a means to stop development of chronic tissue injury and post-traumatic osteoarthritis,” said Dr. Kraus, professor of medicine at Duke University in Durham, N.C. “The early phase of acute joint injury represents a window of opportunity for providing treatment to promote healing and to prevent a subsequent cascade of joint destructive processes.
“We think of osteoarthritis as a slow, chronic disease, but in this type of osteoarthritis it’s not. It’s a critical, acute event that needs acute intervention,” she said in an interview. “This is a curable type of osteoarthritis because you know when it starts. I think we’ll be able to impact the incidence of osteoarthritis following trauma.” New studies should target intra-articular therapy within hours of the traumatic injury, as opposed to the weeks of delay in her pilot study, Dr. Kraus said.
The study enrolled 11 patients younger than 40 within the first month following an MRI-confirmed tear of their anterior cruciate ligament in one knee. The enrolled patients had no history of prior knee injury, and no diagnosis of osteoarthritis or other arthropathy in the joint. Following randomization, six patients received a single, 150-mg intra-articular injection of anakinra, which is an interleukin-1 (IL-1) receptor antagonist that blocks the effects of IL-1, a primary proinflammatory cytokine. The other five patients received saline injections. Anakinra (Kineret) has U.S. approval for the treatment of rheumatoid arthritis by subcutaneous injection, but carries no approval for the treatment of osteoarthritis or for intra-articular injection.
The actual age of the 11 enrolled patients averaged 24 years, with a range of 18-29 years. They received their injections an average of 15 days after their injury, with a range of 6-27 days.
Four days following treatment, patients who received an anakinra injection had significant and clinically meaningful improvements in several measures on the Knee Injury and Osteoarthritis Outcome Score (KOOS), improvements not seen in the placebo patients, she reported. The KOOS measurements at 4 days after treatment served as the study’s primary end point.
The KOOS pain subscore fell by an average of 3.8 points in the anakinra-treated patients, a statistically significant 23% relative improvement, compared with no significant change in the placebo patients. The KOOS activities of daily living subscore showed a similar pattern, falling by a statistically significant average of 10.5 points in the anakinra-treated group, a 46% relative improvement compared with baseline. Prior results found that a change of 8-10 points in this measure corresponded to a clinically significant change following reconstruction of the anterior cruciate ligament, Dr. Kraus said at the congress, sponsored by the Osteoarthritis Research Society International.
The total KOOS score improved by an average of 20 points in the drug-treated patients, a significant 24 % relative improvement, compared with no significant change in the placebo patients.
The anakinra-treated patients also showed strong trends toward further improvements in their total KOOS score and their activity subscore when they underwent another assessment 14 days after their injection, while the placebo patients continued to show no substantial changes. At 14 days, the KOOS activity of daily living subscore had improved by an average of 15.5 points compared with baseline.
The anakinra injections produced no adverse reactions.
One month after treatment, the anakinra-treated patients also showed a statistically significant average drop in serum levels of hyaluronan, a change consistent with a reduction in synovial inflammation in the knee.
The next step is to run a larger study, to administer treatment within a few hours of the acute knee injury, and to test other anti-inflammatory agents. Dr. Kraus said she envisions eventually injecting acutely injured knee joints with a cocktail of anti-inflammatory agents soon after trauma occurs.
Disclosure: Dr. Kraus’s study did not have commercial funding. She said she had no relevant financial conflicts.