VANCOUVER, B.C. – Ixekizumab-treated patients with plaque psoriasis reported markedly faster and larger improvements in itch severity than those on high-dose etanercept or placebo in a large head-to-head phase III randomized trial.
Ixekizumab is an investigational humanized IgG4 monoclonal antibody directed against the proinflammatory cytokines interleukin-17A. In the 1,224-patient phase III UNCOVER-2 trial, itch severity was rapidly reduced in ixekizumab-treated patients as early as week 1, when the first assessment occurred, Dr. Gil Yosipovitch reported at the World Congress of Dermatology.
Moreover, a clinically meaningful itch response – defined by Dr. Yosipovitch and coinvestigators as at least a 4-point drop from baseline on a 0-10 Itch Numeric Rating Scale based upon 24-hour recall – occurred in the ixekizumab-treated patients by week 4. Patients randomized to etanercept (Enbrel) at 50 mg twice per week never reached that bar during the 12-week study. Neither did the placebo-treated controls, noted Dr. Yosipovitch, professor and chairman of the department of dermatology at Temple University in Philadelphia.
The average baseline itch severity score in UNCOVER-2 was 6.6 points. The mean 12-week reduction in itch score was 0.4 points, or 14%, with placebo; 3.6 points, or 51%, with etanercept; 4.9 points, or 75%, with ixekizumab at 80 mg every 4 weeks; and 5.2 points, or 76%, with ixekizumab 80 mg every 2 weeks.
“The most important part of my presentation today is the rapid response to ixekizumab. There’s a significant reduction in itch in the first week and a 75% reduction at 12 weeks. I have to tell you, as someone who’s been in the itch field for a very long time, those are very impressive results,” the dermatologist declared. “Fast improvement is the issue, really. It we want a drug that claims to have an antipruritic effect, it has to work fast, because that’s what really bothers the patient.”
Another impressive statistic: 41% of ixekizumab-treated patients reported “no itching” at 12 weeks, compared with 17% on high-dose etanercept and 2% with placebo, he continued.
A recurring theme at WCD 2015, bolstered by an impressively large survey of North American and European dermatologists, rheumatologists, and patients, is that psoriasis patients feel itch hasn’t gotten the attention it deserves from physicians. Itch is the most common symptom of psoriasis, and more psoriasis patients rate itch as the most bothersome aspect of their chronic inflammatory skin disease than they do any other symptom, Dr. Yosipovitch noted.
Aside from this UNCOVER-2 analysis, very few data exist regarding the antipruritic effects of various biologic agents, he observed.
“I am very excited about this type of approach. Hopefully other companies wil now put more focus on itch. I think this is what the patients want, and if we can achieve fast responses, we are doing our job well,” the dermatologist said.
One audience member asked why the itch score is based upon recall over the previous 24 hours. Why not a week?
Dr. Yosipovitch replied that from other studies he’s done, he has found itch recall beyond 24 hours to be highly problematic.
“I actually recommend doing it twice a day, because itch is not constant throughout the day. It fluctuates. It is worst at nighttime, and that affects quality of life. In trials, I try to have patients keep a diary capturing itch evening and morning,” Dr. Yosipovitch said.
Another audience member asked whether a rapid response to itch might be a biomarker predictive of a later favorable response in terms of lesion size. If so, he continued, perhaps failure to experience a reduction in itch within the first week or so on an agent such a ixekizumab might be a signal to switch to another drug, rather than waiting for 4-8 weeks.
Dr. Yosipovitch replied that it’s an excellent thought and worthy of study, but the answer simply isn’t known yet.
The primary outcomes of UNCOVER-2 have previously been presented (Lancet 2015 June 10 [doi: 10.1016/S0140-6736(15)60125-8]). Briefly, the Psoriasis Area Severity Index (PASI) 75 response rate was 2% with placebo, 42% with etanercept, 78% with ixekizumab every 4 weeks, and 90% with ixekizumab every 2 weeks. When the bar was set higher – a PASI 100 – the response rate was 1% with placebo, 5% with etanercept, and 31% and 41% with ixekizumab every 4 and 2 weeks.
The UNCOVER-2 trial was sponsored by Eli Lilly. Dr. Yosipovitch is a recipient of research grants from and/or a consultant to Eli Lilly and roughly a dozen other pharmaceutical companies.