Conference Coverage

Prior biologic exposure doesn’t diminish ixekizumab’s efficacy


 

REPORTING FROM THE EADV CONGRESS

– Psoriasis patients switched to ixekizumab after previous exposure to another interleukin-17 inhibitor respond as well as those who are IL-17 antagonist naive, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

This finding is of importance in real-world clinical practice because it’s not at all uncommon for psoriasis patients on one biologic to have to switch to another because of insufficient efficacy, side effects, or a change in insurance coverage. Physicians would like to know what sort of responses can be expected to whatever agent they prescribe next.

Ixekizumab smashes psoriasis despites prior use of IL-17 inhibitors
“We’ve seen many cases in which previous use of biologics may detrimentally impact the efficacy of subsequent biologic treatments. It’s a general rule of thumb that patients tend not to respond as well,” noted Dr. Papp, president of Probity Medical Research in Waterloo, Ont.

However, that was not a problem in this secondary analysis of a large clinical trial whose primary purpose was to evaluate the relative safety and efficacy of ixekizumab (Taltz) when dosed every 2 weeks versus every 4 weeks.

“I think what we have seen here is a very compelling story: Previous exposure to biologics – and specifically to IL-17 antagonists – does not impact efficacy when you treat with ixekizumab, nor for that matter does it appear to impact safety,” the dermatologist said.

He reported on 1,227 patients with moderate to severe plaque psoriasis who were randomized to ixekizumab at 80 mg every 2 or 4 weeks following an initial 160 mg loading dose. Among those who started out on ixekizumab every 4 weeks, 306 patients got a per-protocol dose adjustment to biweekly therapy because of an insufficient response to monthly dosing as defined by a Physician’s Global Assessment score of 2 or more on two consecutive office visits during study weeks 12-40.

A total of 939 patients were IL-17 inhibitor naive. The other 288 had previously been on the IL-17 antagonists brodalumab (Siliq) or secukinumab (Cosentyx). The two groups had similar baseline demographics with the exception that the experienced cohort had on average a 22.2-year duration of psoriasis, 3.7 years more than IL-17 antagonist-naive patients.

In an intent-to-treat analysis, Psoriasis Area and Severity Index (PASI) 75, 90, and 100 responses at week 52 didn’t differ significantly between the IL-17 inhibitor-naive and -experienced groups. In fact, patients with prior exposure to other IL-17 antagonists showed a consistent trend for slightly higher response rates (see graphic).

It was clear from this analysis that dosing ixekizumab every 2 weeks provides significantly better efficacy than was dosing every 4 weeks, Dr. Papp noted. Yet the approved dosing is 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.

No new safety issues arose in this study. The only difference between the naive and experienced groups was a lower rate of allergic reactions/hypersensitivity in the experienced group. For example, in patients on ixekizumab every 2 weeks for the entire 52-week study period the incidence of such reactions was 11.5% in the IL-17 antagonist-naive group, compared with 4.1% in the experienced cohort. This isn’t really surprising, according to Dr. Papp.

“Most injection site reactions occur in the newbies,” he said.

The study was sponsored by Eli Lilly. Dr. Papp serves as a consultant and/or adviser to Lilly and numerous other pharmaceutical companies involved in the development of dermatologic therapies.

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