Canakinumab, a monoclonal antibody targeting interleukin-1ß (IL-1ß), may be beneficial to treat patients with osteoarthritis with chronic systemic inflammation.
Matthias Schieker, MD, and a team of investigators suggested further investigation of IL-1ß was needed.
Schieker and colleagues determined whether IL-1ß inhibition with canakinumab reduced incident total hip or knee replacement. In the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS), 10,061 men and women with elevated high-sensitivity C-reactive protein levels and a history of myocardial infarction were randomly assigned to receive either placebo or canakinumab. Patients who received the study drug were given doses of 50, 150, or 300 mg subcutaneously every 3 months for up to 5 years.
CANTOS was conducted between 2011 and 2017 at 1091 clinical sites in 39 countries. Exclusion criteria included: patients with a history of chronic or recurrent infections, previous cancer other than basal cell skin carcinoma, a suspected or known immunocompromised state, a history of tuberculosis or HIV-related disease, and using systemic anti-inflammatory treatments.
The primary and secondary outcomes of CANTOS were time to first incident total hip or knee replacement and time to first occurrence of an osteoarthritis-related adverse event. The investigators assessed the primary end point over a mean follow-up of 3.7 years with a maximum of 5 years. Adverse event outcomes were reviewed by 2 physicians to identify patients of who total hip or knee replacement was attributed to osteoarthritis.
Of the 10,061 patients in the study, 3344 received placebo and 2170 received 50 mg of canakinumab, while 2284 and 2263 participants had 150 or 300 mg doses, respectively. For follow-up, 99.7% of participants had a 12-month visit, 99.5% had a 24- month visit, 88% had a 36-month visit, 82.5% had a 48-month visit, and 60.2% had a 60-month visit.
Among the participants, 15.6% had a reported medical history of osteoarthritis at baseline. Of them, 1369 had peripheral osteoarthritis while the remainder had forms of spinal osteoarthritis.
For those in the canakinumab dose groups, hazard ratios (HRs) for incident total hip or knee replacement during follow-up were .6 (95% CI, .38-.95) for the 50 mg group, .53 (95% CI, .33-.84) for the 150 mg group, and .6 (95% CI, .38-.93) for the 300 mg group, compared to placebo. In a comparison with the placebo group, incidence rates for total hip or knee replacement in the pooled canakinumab groups were .31 and .54 events per 100 person-years (HR, .58; 95% CI, .42-.8; P=.001), respectively. The HR for osteoarthritis-related adverse events was .73 (95% CI, .61-.87).
The findings suggested inhibition of IL-1ß with canakinumab may substantially reduce rates of total hip or knee replacement along with osteoarthritis-related symptoms during a median 3.7 years follow-up. In fact, the data supported the team’s hypothesis that IL-1ß inhibition may represent a novel pathway for future therapies targeting osteoarthritis.
“This secondary analysis of the CANTOS trial presents intriguing results that may offer promise for IL-1 inhibition as a treatment,” Nancy Lane, MD, of UC Davis Health, and David Felson, MD, MPH, of Boston University School of Medicine, wrote in an accompanying editorial.
The 2 noted the findings deserved additional investigation in developing potential disease-modifying osteoarthritis drugs.
The study, “Effects of Interleukin-1ß Inhibition on Incident Hip and Knee Replacement,” was published online in the journal Annals of Internal Medicine.