GENEVA (FRONTLINE MEDICAL NEWS) – Ixekizumab improved fingernail psoriasis significantly faster and with a higher complete nail clearance rate by week 24 compared with ustekinumab in a head-to-head phase 3b randomized trial, Yves Dutronc, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

This is a clinically important finding because – as dermatologists and psoriasis patients well know – nail and skin psoriasis are two different animals.

“Nail involvement is persistent, slow to resolve, difficult to treat, and results in distinct impairment in daily activities,” observed Dr. Dutronc of Eli Lilly in Indianapolis.

He presented a prespecified secondary analysis of the randomized, phase 3b, multicenter IXORA-S trial . The study pit the interleukin-17A inhibitor ixekizumab (Taltz) head-to-head against the interleukin 12/23 inhibitor ustekinumab (Stelara). The primary endpoint, which was the PASI 90 improvement rate, has previously been reported: 73% in the ixekizumab group versus 42% in the ustekinumab group at week 12, and 83% versus 59% at week 24. And ixekizumab’s superior efficacy was achieved with a safety profile similar to that of ustekinumab ( Br J Dermatol. 2017 Oct;177[4]:1014-23 ).

However, change in PASI score or Investigator’s Global Assessment isn’t informative regarding a patient’s change in nail psoriasis status. This was the impetus for the secondary analysis focused on the IXORA-S subgroup with baseline fingernail psoriasis. For this purpose, Dr. Dutronc and his coinvestigators used as their metric the change over time in the Nail Psoriasis Severity Index (NAPSI) total score, which entails a quadrant-by-quadrant assessment of every fingernail.

By play of chance, the 84 patients randomized to ixekizumab had slightly more severe nail psoriasis at baseline than that of the 105 ustekinumab patients. Their mean baseline NAPSI total score was 28.3, compared with 24.8 for the ustekinumab group. More than one-quarter of patients in the ixekizumab arm had a baseline NAPSI score greater than 43, whereas the top quartile of nail psoriasis severity in the ustekinumab group began with a NAPSI score above 34.

Not surprisingly, not much happened in terms of improvement in nail appearance in the first 12 weeks, since new nail grows slowly. But by week 8 the between-group difference in improvement in NAPSI score had become significant in favor of ixekizumab, with a mean 12.9-point reduction from baseline versus a 5.6-point drop in the ustekinumab group. This difference continued to grow over time, such that at week 24 the ixekizumab had a mean 19.9-point reduction, compared with a 13.2-point decrease for the ustekinumab group.

At week 12, 15.5% of the ixekizumab group and 11.3% of the ustekinumab group had reached complete clearance of their fingernail psoriasis. At week 24, complete clearance had been achieved in 48.8% of the ixekizumab group and 22.9% of patients on ustekinumab.

This is an interim analysis. Final results of the IXORA-S nail psoriasis substudy will be reported at 52 weeks of follow-up.

SOURCE: Dutronc Y.