Canakinumab may reduce total knee, hip replacement, OA symptoms
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Interleukin-1 inhibition with canakinumab may substantially reduce rates of total hip and knee replacement, as well as osteoarthritis symptoms, according to data published in the Annals of Internal Medicine.
“Osteoarthritis has not had a new therapy licensed in many years,” Philip Conaghan, MBBS, PhD, FRACP, FRCP, of the University of Leeds, told Healio Rheumatology. “Any new therapy that may reduce patient symptoms — and that is probably why joint replacements were reduced in this study — is highly important. Also, with our aging populations, joint replacement rates are rising dramatically, and health care systems will struggle to cope with this rise in joint replacements. So, a therapy that has the potential to reduce joint replacements is also exciting.”
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To determine whether IL-1 inhibition with canakinumab (Ilaris, Novartis) can reduce incident total hip or knee replacement, Conaghan and colleagues conducted an exploratory analysis of CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study). The CANTOS trial was a multinational, randomized, double-blind, placebo-controlled trial in which 10,061 participants with stable post-myocardial infarction and an hs-CRP level of 2 mg/L or greater received either 50, 100 or 300 mg of canakinumab, or matching doses of a placebo, administered subcutaneously every 3 months.
For their own analysis, Conaghan and colleagues evaluated with time to first total hip or knee replacement, as well as time to first OA-related adverse event, for all participants. The researchers accessed data through blinded review of CANTOS’ clinical and safety records. The median follow-up period was 3.7 years.
According to the researchers, hazard ratios for total hip or knee replacement during the follow-up period were 0.6 (95% CI, 0.38-0.95) for the 50 mg canakinumab group, 0.53 (95% CI, 0.33-0.84) for the 150 mg group and 0.6 (95% CI, 0.38-0.93) for the 300 mg group, compared with placebo. Taken together, the incidence rates for total hip and knee replacement were 0.31 and 0.54 events per 100 person-years (HR = 0.58; 95% CI, 0.42-0.80), respectively, for the canakinumab groups compared with placebo. The hazard ratio for OA-related adverse events was 0.73 (95% CI, 0.61-0.87). The researchers noted similar findings in analyses restricted to participants with a history of OA.
“Firstly, this study tells us that pharmacological treatment of inflammation leads to reduced joint replacements, presumably by an effect on osteoarthritis pain,” Conaghan said. “It’s unclear if the inflammation that was treated was at the joint level, systemic inflammation, or both. We do not know if there were any effects on joint structure. The exciting finding here is that we are opening up a new field of understanding in the causes of osteoarthritis pain and consequently potential treatments.”
Perspective
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Barbara Kienzle, BSN, RN
Osteoarthritis is a painful progressively debilitating condition with few effective treatments, often leading to total joint replacement surgery. Chronic joint inflammation is a common component of OA with interleukin-1 (IL-1B) identified as a critical cytokine involved in this process.
Schieker and colleagues performed a deep dive into the statistics from CANTOS, Canakinumab Anti-inflammatory Thrombosis Outcomes Study, to determine if inhibition of IL-1B with canakinumab reduces the incidence of total hip/knee replacement in patients with OA. Results of this tedious process indeed indicated a decrease in joint replacement and length of time until joint replacement is indicated with use of canakinumab vs. placebo.
Although the conclusions drawn by Schieker and colleagues was not sufficient to recommend canakinumab as a treatment for OA, ample evidence was presented to move forward with targeted studies focused on the effectiveness of IL-1B inhibition as a novel treatment for patients with OA.
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