Canakinumab shows promise for osteoarthritis

The interleukin (IL)-1β inhibitor canakinumab substantially reduces the need for total hip or knee replacement for osteoarthritis, according to a secondary analysis of the CANTOS trial.

“Few effective and tolerated symptomatic therapies for osteoarthritis exist other than joint replacement surgery, and no structure-modifying drugs are [currently] available,” the researchers stated.

CANTOS, a large, multinational, double-blind trial, originally tested canakinumab as a therapy for secondary prevention of cardiovascular (CV) disease in 10,061 post-myocardial infarction patients with elevated inflammation (hs-CRP* ≥2 mg/L). 

IL-1β has been implicated in the osteoarthritis inflammatory process by inducing mediators that drive cartilage destruction and increase pain. Therefore, the hospitalization data collected during the main trial provide an opportunity to conduct an exploratory analysis of IL-1β inhibition in osteoarthritis.

After a median follow-up of 3.7 years, the risk of incident total hip/knee replacement was lower by 33–40 percent with the three doses of canakinumab vs placebo (hazard ratios [HRs], 0.60, 0.53, and 0.60 for the 50-, 150-, and 300-mg canakinumab groups). [Ann Intern Med 2020;173:509-515] 

When all three canakinumab groups were pooled, the incident rate for total hip/knee replacement was significantly reduced compared with the placebo group (0.31 vs 0.54 events per 100 person-years; HR, 0.58; p=0.001).

“The results of this exploratory trial are both unexpected and exciting,” wrote Dr Nancy Lane and David Felson from UC Davis Health, Sacramento, California, and Boston University School of Medicine in Boston, Massachusetts, US, respectively, in a linked editorial. [Ann Intern Med 2020;173:580-581] 

“The reduction in joint replacements among patients who received canakinumab vs the placebo group became apparent after only 1 year of treatment,” they noted.

The secondary outcome of osteoarthritis-related adverse events occurred at a rate of 1.17 vs 1.63 per 100 person-years for pooled canakinumab groups vs placebo (HR, 0.73, 95 percent confidence interval [CI], 0.61–0.87).

Restricting the analysis to patients with a history of osteoarthritis at baseline did not change the results (HR, 0.66, 95 percent CI, 0.51–0.87).  

“These data thus provide support for the hypothesis that IL-1β inhibition might represent a novel pathway for future therapies targeting osteoarthritis … [and] support further investigation of IL-1β inhibition for treatment of large joint osteoarthritis,” the researchers concluded.

As CANTOS was not originally designed to study canakinumab in osteoarthritis, data such as structural outcomes, radiographic progression, functional status, and pain control were not systematically collected.

“The investigators used elevated hs-CRP level as an entry criterion. This requirement, not routine in osteoarthritis trials, may have identified a subgroup of persons with osteoarthritis in whom inflammatory cytokines activate pathways that accelerate joint degeneration,” explained Lane and Felson. 

“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,” they suggested.