Serum ustekinumab levels were an effective early measure of psoriasis treatment response, according to study data published in JAMA Dermatology.
The Biomarkers of Systemic Treatment Outcomes in Psoriasis recruited adults with psoriasis from 60 participating centers in the United Kingdom. The analysis included patients undergoing ustekinumab monotherapy who provided at least one serum sample during the first year of treatment. Clinical response was assessed longitudinally using the Psoriasis Area and Severity Index (PASI) score. As outcome measures, investigators captured the percentage of patients achieving a 75% reduction in baseline PASI score (PASI75), the percentage achieving a 90% reduction (PASI90), and the percentage achieving an absolute PASI score of 1.5 or less. Multivariable logistic regression models were used to identify associations between serum ustekinumab levels and each outcome. Analyses were adjusted for patient age, baseline PASI score, and baseline ustekinumab dose.
A total of 491 patients (65.2% men; mean [SD] age, 45.7 [12.8] years) provided one or more serum samples within 56 weeks of treatment initiation. Overall, 853 serum samples were obtained. The majority of patients were receiving 45 mg of ustekinumab (57.4%), while 42.6% received 90 mg. In total, 348 patients (70.9%) achieved PASI75 within a year of starting treatment. Patients achieving PASI75 at 6 months had higher early ustekinumab levels (median, 2.78 μg/mL; interquartile range [IQR], 1.78-4.02 μg/mL) compared with patients not achieving PASI75 (median, 1.83 μg/mL; IQR, 0.96-2.86 μg/mL). In regression analyses, higher drug levels after 1 to 12 weeks of treatment were significantly associated with higher odds of PASI75 response at 6 months (odds ratio [OR], 1.38; 95% CI, 1.11-1.71; P =.004). However, the same trend was not observed for achieving PASI90 or a PASI score ≤1.5. Antidrug antibodies were detected in just 17 of 490 patients (3.5%), suggesting low levels of drug immunogenicity.
These data support the utility of serum ustekinumab monitoring to forecast treatment response, the investigators reported, as achieving adequate drug exposure early on may be crucial to treatment response. As a trial limitation, investigators cited difficulties in accounting for ustekinumab’s extended dosing interval; serum levels alone may not be an inclusive measure of total drug exposure. “Further investigation to confirm the clinical utility of [therapeutic drug monitoring] of ustekinumab and other biologics is a key step toward personalization of treatment regimens across multiple immune-mediated inflammatory diseases,” the study investigators concluded.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
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