IL-1 inhibition warrants further investigation for osteoarthritis
medwireNews: Treatment with the interleukin (IL)-1β inhibitor canakinumab is associated with a reduced incidence of total joint replacement, suggests an exploratory analysis of the CANTOS trial.
This “unexpected and exciting” finding “deserves additional investigation in developing potential disease-modifying osteoarthritis drugs,” say the authors of an editorial accompanying the research published in the Annals of Internal Medicine.
Paul Ridker (Brigham and Women's Hospital, Boston, Massachusetts, USA) and co-researchers analyzed data from 10,061 people with elevated high-sensitivity C-reactive protein (hs-CRP; ≥2 mg/L) and a history of myocardial infarction who were randomly assigned to receive canakinumab (50, 150, or 300 mg every 3 months). The average age of participants was approximately 61 years, and three-quarters were male.
In all, there were 79 total hip or knee replacements during a median follow-up of 3.7 years among 6717 patients treated with canakinumab at any dose, compared with 68 procedures among 3344 patients given placebo.
These findings translated into event rates of 0.31 and 0.54 per 100 person–years, respectively, and a significant 42% reduced risk for joint replacement in the canakinumab group. This risk reduction was significant with all the doses of canakinumab studied, ranging from 40% with the 50 mg and 300 mg doses to 47% with the 150 mg dose.
Ridker and team say that “similar benefits” of canakinumab versus placebo were seen in the subgroup of 1369 patients with peripheral osteoarthritis at baseline, with a significant 43% reduced risk for joint replacement with any dose of canakinumab versus placebo.
Moreover, patients in the canakinumab arm were significantly less likely to experience worsening osteoarthritis symptoms or new osteoarthritis adverse events than those in the placebo arm, and these findings held true both in the total study population and in the subgroup with peripheral osteoarthritis.
Editorialists Nancy Lane (UC Davis Health, Sacramento, California, USA) and David Felson (Boston University School of Medicine) point out that the study findings contrast those of four previous trials showing no significant impact of IL-1 inhibitors on knee osteoarthritis pain during 4–50 weeks of follow-up.
They note that the current study “used elevated hs-CRP level as an entry criterion,” a requirement that is “not routine in osteoarthritis trials [and] may have identified a subgroup of persons with osteoarthritis in whom inflammatory cytokines activate pathways that accelerate joint degeneration.”
And the editorialists conclude: “Further studies should evaluate the importance of elevated CRP levels as a factor affecting response to treatment, include more women to better reflect the osteoarthritis population, explore how to minimize infections, and try to better define the duration of therapy needed to detect treatment effects.”
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