Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
In osteoarthritis (OA), there are no therapeutics to prevent disease progression. Canakinumab, a monoclonal antibody targeting interleukin-1β, reduced inflammation and cardiovascular events in the CANTOS trial (Ridker et al. 2017). CANTOS included 10,061 men and women with a history of myocardial infarction and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L who were randomized to placebo or one of three doses of canakinumab (50 mg, 150 mg, or 300 mg) given sc once every 3 months. Median follow-up was 3.7 years.
We conducted a post-hoc exploratory analysis of CANTOS data to evaluate potential effects of canakinumab on rates of OA-related adverse events (AE) and incident TKR/THR (ARGUS) in the full CANTOS cohort and in a subgroup with a medical history of OA. The high-level term Osteoarthropathy (OAP) was used to search the AE database, (no adjudication of OA was pursued). A time to event analysis was done for first occurrence of TKR/THR as well as for OAP related AEs. The drug treated groups were compared to placebo by two-sided log-rank test. Second, the analyses were repeated with pooled drug treated groups and hazard ratios for pooled drug vs placebo computed by Cox proportional hazards regression (CPH).
In all patients, incidence rates of TKR/THR were 1.41%, 0.88%, 0.66%, and 0.80% in the placebo and canakinumab 50 mg, 150 mg, and 300 mg groups, respectively. The relative risk reduction (RRR) for pooled treatment vs placebo was 45% computed by CPH, p<0.001. For OA related adverse events, comparable incidence rates were 7.0%, 5.2%, 5.1%, 6.0%, respectively. The RRR for pooled treatment vs. placebo was 23% computed by CPH, p=0.002. In the subgroup of 1569 CANTOS participants with OAP at baseline, incidence rates of TKR/THR were 6.25% and 3.36% in the placebo and combined canakinumab groups respectively (RRR vs placebo 45%, p<0.013, Figure 1). Incidence rates for OA related adverse events were 20.7%, 16.6%, 12.4%, 15.0%, respectively (RRR vs. placebo across groups 31%, p=0.003, Figure 2).
In an exploratory analysis of the CANTOS trial, canakinumab treatment was associated with reduced rates of THR/TKR and OA symptoms. Effects were most apparent among those with a prior history of OA. An additional responder analysis based on hsCRP lowering at 3 months is currently ongoing.
Ridker PM, Everett BM, McFadyen JG, et al., Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119-31
To cite this abstract in AMA style:Schieker M, Mindeholm L, Praestgaard J, Scotti C, Solomon D, Thuren T, Dreyer K, Roubenoff R, Ridker PM. Interleukin-1β Inhibition with Canakinumab Associates with Reduced Rates of Total Hip and Knee Replacement (THR/TKR) and Osteoarthritis (OA) Symptoms: Exploratory Results from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/interleukin-1%ce%b2-inhibition-with-canakinumab-associates-with-reduced-rates-of-total-hip-and-knee-replacement-thr-tkr-and-osteoarthritis-oa-symptoms-exploratory-results-from-the-canakinumab-ant/. Accessed May 20, 2019.
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