Circulating Brodalumab Levels Associated with Treatment Response in Psoriasis

Christian Enevold, PhD

A new case series study from Copenhagen suggested that circulating brodalumab levels were associated with clinical treatment response in patients with psoriasis. Investigators added that monitoring these levels could aid clinical decision-making and prevent ineffective therapy.

In recent years, biologic therapies such as brodalumab have broadened treatment options for patients with psoriatic disease. However, some patients have been shown to either not respond or lose response over time to these therapies, and adverse effects have included suicidal ideation and behavior.

As such, a prominent challenge for health care providers and patients alike has been determining which patients would truly benefit from biologic therapies such as brodalumab.

Christian Enevold, PhD, Institute for Inflammation Research, Copenhagen University Hospital, and fellow investigators retrospectively measured trough levels of circulating brodalumamb and antidrug antibodies in patients with prior failure to ant-IL-17A therapy to assess whether the brodalumab levels were associated with clinical response.

Between May 2018 and June 2020, investigators recruited patients from the Departments of Dermatology at Gentofte and Aarhus University Hospitals. None of the patients recruited for the study received concomitant systemic treatment for psoriasis, and all patients had baseline PASI score of 6 or higher and experienced treatment failure receiving at least one IL-17A prior to inclusion.

To avoid overlapping treatment, all systemic therapies were discontinued 4 weeks prior to baseline, and baseline PASI score were assessed prior to initiating brodalumab 210 mg at weeks 0,1, 2, and every 2 weeks.

Investigators assessed PASI immediately before every dosing to measure trough levels of the biologic in addition to cytokines after 4, 12, 26, and 52 weeks of therapy. Patients who did not show PASI improvement of 75% from baseline had treatment discontinued and left the study, and those who discontinued treatment for any reason were considered non-responders. Meanwhile, patients who maintained a PASI 75 response were followed up for 52 weeks.

Among the 20 patients recruited into the study, 65% were made, and the median age of all patients was 50 years.

Investigators observed that patients with quantifiable levels of brodalumab (0.05 μg/mL) following 12 weeks of therapy experienced significantly higher PASI reductions that those without ((P=.006).

Notably, 4 of the 5 patients (80%) who had not achieved PASI 75 had sub-quantifiable drug levels, which was a finding that was only observed in 3 of 14 PASI 75 responders. Those with sub quantifiable drug levels after 12 weeks of therapy maintained the response, and no anti-brodalumab antibodies were detected in any of the tested samples.

Though the study was limited to a small sample size, an association between circulating brodalumab levels and treatment responses in patients with psoriasis was determined.

“Monitoring patient levels of circulating brodalumab may aid clinical decision-making and help prevent ineffective therapy,” the team wrote.