Early Levels of Ustekinumab May Predict Longer-term Response in Patients With Psoriasis

While new biologic therapies have transformed care for patients with immune-mediated inflammatory diseases, there is a wide variation in response to these high-cost drugs. However, measurement of early drug levels may successfully be used to direct treatment strategy, according to a new study in JAMA Dermatology that evaluated the clinical utility of drug monitoring for ustekinumab to treat psoriasis.¹

The study included 491 British adults with psoriasis who were recruited from the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study as part of the British Association of Dermatologists Biologic and Immunomodulators Register. A total of 853 samples were obtained from the start of treatment.

The researchers measured disease activity using the Psoriasis Area and Severity Index (PASI) score. At least 1 PASI score was collected within the first year of treatment.

Early measured drug levels had a statistically significant association with 6-month response. Within 12 weeks after starting treatment, measured drug levels were associated with PASI75 (75% reduction in PASI score from baseline) 6 months after treatment started. The researchers reported that drug immunogenicity was low, with antidrug antibodies only detected in 17 (3.5%) of the patients.

“This finding suggests that adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome with ustekinumab,” the authors wrote. They did suggest that additional research should focus on “pharmacokinetic-pharmacodynamic modeling of the whole time course of response to ustekinumab.”

In addition, they noted that further research is needed to confirm the use of therapeutic drug monitoring for ustekinumab.

In an accompanying editorial,² Andrew Blauvelt, MD, MBA, of Oregon Medical Research Center, pointed out that although there are newer biologics available for psoriasis, there are a subset of patients who do well on older biologics and nonbiologic therapeutic options. The importance of this new study is that it helps identify which patients will respond to older and less expensive therapeutic options.

“The results also bring us 1 step closer toward personalized medicine, an ideal type of future medical practice where all therapies would be chosen based on characteristics (eg, genetic, demographic, biologic) unique to a given individual patient,” he wrote. “Personalized medicine could assure that each chosen medication is tailored for a given patient, thus optimizing chances for therapeutic success.”

References

1. Tsakok T, Wilson N, Dand N, et al. Association of serum ustekinumab levels with clinical response in psoriasis [published online September 18, 2019]. JAMA Dermatol. doi: 10.1001/jamadermatol.2019.1783.

2. Blauvelt A. Predicting clinical responses to ustekinumab: progress toward a future of personalized medicine [published online September 18, 2019]. JAMA Dermatol. doi: 10.1001/jamadermatol.2019.2587.