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Secukinumab found ineffective in treating Crohn’s disease
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Anti-interleukin-17A monoclonal antibody secukinumab did not effectively treat patients with Crohn’s disease and was associated with higher rates of adverse events in a recent study.
In a double blind, placebo-controlled proof-of-concept trial, 59 patients with moderate-to-severe Crohn’s disease randomly received either 10 mg/kg intravenous secukinumab (n=39) or placebo (n=20) administered on the 1st and 22nd days of the study. Researchers evaluated the degree of symptom improvement according to the Crohn’s Disease Activity Index (CDAI) after 6 weeks of treatment compared with placebo, and also tested 35 genetic polymorphisms to determine association with response in a 24-patient subgroup.
Twelve patients (31%) in the treatment group stopped treatment early, compared with six in the placebo group (30%). Among these patients, 10 discontinued treatment owing to lack of therapeutic effect, including eight (21%) in the treatment group and two (10%) in the placebo group. Seventeen patients in the treated group developed 20 infections compared with none in the placebo group, and serious adverse events (SAE) were experienced by seven treated patients compared with three receiving placebo within 18 weeks of treatment initiation. SAE included five incidents of worsening Crohn’s disease, four of which occurred in the treatment group.
Investigators estimated a probability of less than 0.1% that secukinumab reduced CDAI by 50 points or more compared with placebo (difference in mean CDAI (SD)=33.9 (19.7); 95% credible interval, –4.9 to 72.9), and area under the curve analysis of weeks 4 through 10 following treatment favored placebo (mean change in CDAI=49; 95% CI, 2-96). In the 24-patient subgroup analysis, participants with elevated inflammatory markers were more likely to experience poor response (mean change in CDAI=62; 95% CI, –1 to 125), and a strong association was found between nonresponse to treatment and the absence of a minor allele of tumor necrosis factor-like ligand 1A (P=.00035).
“Inhibition of IL-17A by secukinumab was ineffective in this trial of patients with moderate to severe Crohn’s disease,” the researchers concluded. “Compared with placebo, secukinumab had a smaller effect and patients on secukinumab showed higher rates of adverse events. However, this was a small exploratory study, and adverse outcomes … were not seen in trials of secukinumab in other indications. It may be that IL-17A has a protective function in inflammatory Crohn’s disease, possibly more pronounced in patients without the minor TL1A variant (rs4263839A).”
Disclosure: See the study for a full list of relevant disclosures.
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