Major Finding: A single, 150-mg intra-articular injection of anakinra an average of 15 days after knee injury led to a statistically and clinically significant 10.5-point improvement in the KOOS activity of daily living score 4 days after injection. Patients receiving a placebo injection showed no significant improvement.
Data Source: Randomized, placebo-controlled pilot study with 11 patients.
Disclosures: Dr. Kraus's study did not have commercial funding. She said she had no relevant financial conflicts.
BRUSSELS — The clinical response seen to injection of a targeted anti-inflammatory drug into an acutely damaged knee joint within a few weeks of injury in a controlled pilot study with 11 patients provided a step toward the development of a new approach to treating traumatic joint injury.
“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.
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. 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 age of the 11 patients averaged 24 years (range, 18–29 years). They received their injections an average of 15 days after their injury (range, 6–27 days).
Four days after 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 placebo patients, she reported.
The KOOS pain subscore fell by an average of 3.8 points in anakinra-treated patients, a statistically significant 23% relative improvement, compared with no significant change in placebo patients. The KOOS activities of daily living subscore showed a similar pattern, falling by a statistically significant 10.5 points in the anakinra-treated group, a 46% relative improvement compared with baseline.
Prior results showed that a change of 8–10 points in this measure corresponded to a clinically significant change after 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 total KOOS score and activity subscore when they underwent another assessment 14 days after their injection, while the placebo patients continued to show no substantial changes.