Early C-reactive protein 'not a good biomarker' for canakinumab impact on gout flares
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Early reduction in high-sensitivity C-reactive protein is “not a good biomarker” for canakinumab’s protective impact on future gout flares, according to data published in Arthritis Care & Research.
However, results from a prevalent gout subgroup suggest there may be a potential role for using reduced early high-sensitivity CRP as a biomarker for interleukin-1 inhibition benefiting future gout flares, the researchers noted.
“In the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS), the anti-interleukin-1 agent canakinumab showed a cardiovascular benefit as well as reduction in gout flares or attacks,” Kazuki Yoshida, MD, ScD, of Harvard Medical School and Brigham and Women’s Hospital, in Boston, told Healio Rheumatology. “However, some patients still experienced gout flares despite regularly administered canakinumab, indicating individual variability in therapeutic response.”
To analyze the value of early high-sensitivity C-reactive protein (hsCRP) reduction as a biomarker for canakinumab (Ilaris, Novartis) protecting against future gout flares, Yoshida and colleagues conducted a post-hoc causal mediation study of data from CANTOS. The mediator of interest was the 3-month change in log hsCRP. The researchers used linear regression for the hsCRP mediator and Cox or Weibull regression for gout flare outcomes, combining them for the causal mediation analysis.
Yoshida and colleagues included a total of 9,221 patients without prevalent gout, and 747 with prevalent gout at baseline, in their analysis. They examined both the overall cohort as well as a subgroup stratified by baseline prevalent gout.
According to the researchers, the Cox regression HR for gout flare was 0.5 (95% CI, 0.37-0.68) comparing canakinumab with placebo, of which just 6% was explained by the mediated effect through reduced hsCRP during the first 3 months. Meanwhile, in the subgroup of patients with prevalent gout, the hazard ratio was 0.58 (95% CI, 0.36-0.95), of which 31% was explained by the mediated impact through hsCRP reduction. The Weibull analysis demonstrated a proportion mediated estimate of 47%. The indirect impact of reducing hsCRP was unclear among those without prevalent gout.
“The early reduction in hsCRP was not a good biomarker for canakinumab’s protective effect on the first gout flares,” Yoshida said. “However, in patients with an existing diagnosis of gout, the early reduction in hsCRP explained 31% of the protection from further gout flares, suggesting its potential role as a treatment benefit biomarker.
“This is a proof-of-concept study because canakinumab has a limited role in gout care due to its cost,” he added. “However, hsCRP may serve as a treatment benefit biomarker both for future gout flares — among gout patients — and cardiovascular events — shown in previous studies. It is of interest whether the same holds true for more affordable anti-inflammatory medications that likely have beneficial effects in both gout and cardiovascular disease, such as colchicine.”
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