Elevated CRP levels may point to better secukinumab response in AS patients
medwireNews: Ankylosing spondylitis (AS) patients with elevated C-reactive protein (CRP) levels may experience greater benefits from treatment with the interleukin (IL)-17A inhibitor secukinumab than those with lower levels of the inflammatory marker, researchers report.
However, Jürgen Braun (Ruhr-University Bochum, Herne, Germany) and co-investigators emphasize that “patients with normal baseline CRP levels also have a strong likelihood of experiencing a positive treatment response with IL-17A inhibition.”
In their post-hoc analysis, Braun and colleagues found that 63.5% of 392 patients who were treated with either secukinumab 150 mg or placebo every 4 weeks in the MEASURE 1 and 2 trials had elevated CRP levels (≥5 mg/L) at baseline.
They report that a significantly higher proportion of patients treated with secukinumab versus placebo achieved an ASAS20 response at week 16 in both the elevated and normal CRP groups, but “the magnitude of response [was] higher in patients with increased baseline CRP.”
Specifically, ASAS20 response rates with secukinumab versus placebo treatment were 63.2% versus 29.0% in the elevated CRP group, and 56.9% versus 28.2% in the normal CRP group. The corresponding ASAS40 response rates were 42.4% versus 15.3% and 34.7% versus 7.0%, and average improvements in BASDAI score were 2.4 versus 0.6 points and 2.2 versus 1.0 points, respectively.
When participants were categorized using a CRP cutoff of 10 mg/L, ASAS20 response rates were 72.4% for secukinumab-treated patients and 28.0% for placebo-treated patients among those with levels at or above this cutoff (45.9% of all participants), and were 51.8% and 29.4%, respectively, for those with levels below 10 mg/L.
The researchers also demonstrated an association between decreasing CRP levels and response to secukinumab treatment. Among the 168 patients who experienced at least a 50% reduction in CRP during the first 4 weeks of the study, those treated with secukinumab experienced significantly higher ASAS20 response rates than those given placebo (72.1 vs 35.7%). However, the difference in ASAS20 response rates between the secukinumab and placebo groups was no longer statistically significant among patients who did not experience a 50% decrease in CRP levels (33.3 vs 27.9%).
“To what extent those patients [without an early decrease in CRP levels] could benefit from an increased dose of secukinumab after week 4 is an open question,” write the study authors in RMD Open.
And they conclude: “Inclusion of prospectively planned analyses by baseline CRP level in future clinical trials would help guide treatment strategies for patients with AS with normal, as well as elevated, baseline CRP.”
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