Secukinumab yields sustained positive effects on molecular, histopathologic psoriasis markers

Treatment with secukinumab leads to sustained clinical response among patients with psoriasis, with clinical response being associated with rapid and persistent normalization of keratin 16 (K16) and inflammatory gene expression for most patients, according to data from the ObePso-S study.

ObePso-S included 82 patients who were grouped according to their body weight (<90 or ≥90 kg). They were randomly assigned to receive either secukinumab 300 mg (n=54) or placebo (n=28) for 52 weeks. At week 12, patients receiving placebo were switched to secukinumab.

Study endpoints included Psoriasis Area and Severity Index improvement of 90% (PASI90) and Investigator’s Global Assessment modified 2011 0/1 responses, which were evaluated at weeks 12 and 52. Lesional and nonlesional skin biopsies were collected at baseline, week 12, and week 52. These samples were subjected to immunohistochemistry for K16 and gene expression profiles.

More than half of the patients who received secukinumab achieved PASI90 at week 12 (55.8 percent) and at week 52 (59.6 percent). K16 was not detected in biopsy samples from 93.1 percent of week 12 PASI90 responders and those from 93.6 percent of week 52 PASI90 responders. These findings reflected the downregulated expression of psoriatic inflammation.

Among week 52 PASI90 nonresponders, on the other hand, clinical and inflammatory marker responses dropped to baseline levels. Inadequate control of inflammatory gene expression at week 12 correlated with suboptimal clinical responses at week 52.