Review Outlines Pharmacologic Properties Secukinumab, Future Personalization Opportunities

Secukinumab (Cosentyx) has become a widely used therapy for patients with psoriatic diseases. A new review of existing literature pertaining to the drug argues a full understanding of its pharmacological properties can help clinicians improve patient outcomes.

Secukinumab is a fully human monoclonal IgG1/κ antibody that selectively targets interleukin (IL)-17A and is indicated for the treatment of moderate to severe psoriasis (PsO), psoriatic arthritis (PsA), and radiographic and nonradiographic axial spondyloarthritis (axSpA). The drug was first developed back in 2001 and has been on the market for more than 6 years.

Writing in the journal Pharmacology & Therapeutics, corresponding author Frank Kolbinger, PhD, of the Novartis Institutes for Biomedical Research, and colleagues, said it is important to understand the pharmacological, molecular, and functional properties of biologics like secukinumab, since this information can be helpful in understanding which therapies are best suited to certain patients.

“Although clinical data guide treatment decisions, the pharmacological properties of biologics provide complementary insight into the potential clinical efficacy and safety profiles of these drugs,” they wrote.

In outlining the literature, Kolbinger and colleagues said the drug has now been around long enough that the interplay between the therapy’s pharmacokinetic (PK) and pharmacodynamic (PD) properties is well-understood. They said continuous dose optimization can help achieve ideal clinical responses in patients.

“The favorable PK/PD profile of secukinumab leads to long-term drug survival and sustained efficacy over long treatment periods in clinical studies and real-world use,” they said.

The biologic has a very low rate of antidrug antibody responses, with rates below 1%, and injection-site reactions across indications, the investigators found. Since the drug was approved, some 680,000 patient-years’ worth of exposure have been reported, and the authors said none of that real-world usage has led to any new safety signals. Thus, they said, secukinumab appears to pass one of the most important considerations—long-term safety—for most patients.

The investigators closed with a discussion of the therapy’s personalized medicine implications, particularly given that there is an increasing number of biologics being approved to treat psoriatic diseases and axial spondyloarthritis. They said the expanding menu of therapeutic options could lend itself to a more tailored prescription approach.

“Duration of disease and patient history may influence the clinical response, and early treatment may be beneficial for optimal response and prevention of disease progression—for example, from PsO to PsA,” they wrote. “Distinct endotypes or disease domain manifestations of psoriatic disease or axSpA may respond differentially to drugs with different mechanisms of action.”

Kolbinger and colleagues said machine learning might become a tool to determine the best therapy for an individual case. In fact, they said, research is already underway to see how different endotypes respond to specific tumor necrosis factor-α inhibitors or IL-17A inhibitors.

“To realize effective, personalized treatment approaches for each patient, a thorough understanding of clinical and pharmacological data for biologics must be developed,” they concluded.

Reference:

Kolbinger F, Di Padova F, Deodhar A, et al. Secukinumab for the treatment of psoriasis, psoriatic arthritis, and axial spondyloarthritis: physical and pharmacological properties underlie the observed clinical efficacy and safety. Pharmacol Ther. Published online June 23, 2021. doi:10.1016/j.pharmthera.2021.107925