Damian McNamara

October 05, 2016

VIENNA — In patients with psoriasis, ixekizumab (Taltz, Lilly) is more effective at 12 weeks than ustekinumab (Stelara, Janssen), according to a randomized direct-comparison study of the two biologic agents.

However, itch, skin pain, and treatment-emergent adverse events were not significantly different between the two drugs.

"Ixekizumab joins the club of interleukin [IL]-17A inhibitors showing superiority to one the world's best biologics in psoriasis to date, ustekinumab," said Kristian Reich, MD, from Dermatologikum Hamburg in Germany.

When a new class of biologics enters the arena, people often ask, "What more do we get?" Dr Reich told Medscape Medical News. "That's a very justifiable question, and the best way to answer it is to do a direct head-to-head trial."

He presented results from the phase 3b IXORA-S study here at the 25th European Academy of Dermatology and Venereology Congress.

In two previous studies Dr Reich was involved with — UNCOVER-2 and UNCOVER-3 — ixekizumab, a high-affinity monoclonal antibody that selectively targets IL-17A, was shown to be more effective than etanercept and placebo in patients with moderate to severe psoriasis (Lancet. 2015;386:541-551).

In IXORA-S, Dr Reich and his colleagues randomized 136 patients to ixekizumab 160 mg at baseline followed by 80 mg every 2 weeks for 12 weeks, and 166 patients to the IL-12 and IL-23 inhibitor ustekinumab, dosed by weight according to the label.

Mean Psoriasis Activity Severity Index (PASI) scores at baseline were about 19.8 to 19.9, so "patients were severely affected by their psoriasis," Dr Reich reported.

Many participants complained of itch; mean score on the itch numeric rating scale was 6.2 at baseline. Mean weight in the study cohort was 85 to 90 kg, mean age was 42 to 44 years, and about two-thirds of the cohort was male.

The primary end point was a 90% improvement in psoriasis (PASI 90) at 12 weeks. This threshold was chosen instead of a 75% improvement (PASI 75) because "more patients who achieve PASI 90 say they are no longer controlled by their psoriasis," Dr Reich explained.

Table. IXORA-S Patient Responses at 12 Weeks

Response Ixekizumab, % Ustekinumab, % P Value
PASI 75 91 69 <.001
PASI 90 75 42 <.001
PASI 100 37 15 <.001
Static Physicians Global Assessment score of 0 43 18 <.05
Dermatology Life Quality Index score of 0 or 1 63 45 <.001

 

On logistic regression analysis, PASI 75 was achieved by significantly more patients in the ixekizumab group than in the ustekinumab group, after adjustment for weight, affected region, disease severity, and other factors (P < .001).

There were no significant differences between groups on the itch 4-point response, the itch numeric rating scale, or the skin pain visual analogue scale (P > .05).

Rates of treatment-emergent adverse events were similar in the ixekizumab and ustekinumab groups (56% vs 63%; P = .288).

 
It will be interesting to see what goes on at week 24 and at 1 year.
 

The fact that the study was only 12 weeks is a potential limitation, Dr Reich acknowledged. "It will be interesting to see what goes on at week 24 and at 1 year."

After his presentation, Dr Reich was asked whether participants who had previously been treated with tumor necrosis factor (TNF) inhibitors were included in IXORA-S.

"They were allowed. Both drugs will work in patients who not only previously used anti-TNFs, but also in those who failed anti-TNFs, but their response will be lower," he reported. "That is a general pattern we see."

"Nowadays, there are a lot of therapeutic options for psoriasis," said session cochair Giovanna Zambruno, MD, from the Istituto Di Ricovero e Cura a Carattere Scientifico in Rome.

"This study compared two very good biologics that target different interleukins," he told Medscape Medical News.

Although the comparison favored ixekizumab, ustekinumab has demonstrated maximum activity beyond 12 weeks; therefore, the study duration was not sufficient, said Dr Zambruno.

The IXORA-S study was sponsored by Eli Lilly and Co. Dr Reich has served as an advisor, paid speaker, and participated in clinical trials sponsored by Lilly and Janssen-Cilag. Dr Zambruno has disclosed no relevant financial relationships.

25th European Academy of Dermatology and Venereology (EADV) Congress: Abstract D3T01.1K. Presented October 1, 2016.

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