Taltz (ixekizumab) is indicated for the treatment of moderate to severe plaque psoriasis in patients who are candidates for systemic therapy. The recommended dose is 160mg by subcutaneous injection at week 0, followed by 80mg every other week starting 2 weeks after the initial dose for 12 weeks. The recommended maintenance dose is 80mg every 4 weeks; treatment should be reassessed if there is no response after 16 to 20 weeks.
The efficacy and safety of ixekizumab were assessed in three randomised, double-blind, phase III trials (UNCOVER-1, -2 and -3).
In the UNCOVER-1 trial (n=1296) patients were randomly assigned to receive ixekizumab 80mg every 2 weeks or 80mg every 4 weeks (both after a starting dose of 160mg at week 0), or placebo. In the UNCOVER-2 (n=1224) and -3 (n=1346) trials, participants were randomly assigned to the same treatment groups, with an additional group receiving etanercept 50mg twice weekly.
In the UNCOVER-1 and -2 trials patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 or 1) at week 12 entered a randomised withdrawal period where they were randomly assigned to receive ixekizumab 80mg every 4 weeks, 80mg every 12 weeks, or placebo through week 60. In the UNCOVER-3 trial, patients entered a long-term extension period at week 12 where they received ixekizumab 80mg every 4 weeks until week 60.
The co-primary endpoint for all three studies was a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and an sPGA score of 0 or 1 at week 12.
In the UNCOVER-1 trial all primary endpoints were met with significantly greater improvements in the ixekizumab groups than in the placebo group. Response rates were highest in the 2-week dosing group. Among patients in the 2-week dosing group, 89.1% had a PASI 75 response and 81.8% had an sPGA score of 0 or 1 at week 12, compared with 82.6% and 76.4%, respectively in the 4-week group and 3.9% and 3.2%, respectively in the placebo group (p less than 0.001 for all comparisons of ixekizumab with placebo).
Similar results were observed in the UNCOVER-2 and -3 trials with ixekizumab given in either regimen showing greater efficacy, as measured by PASI 75 and sPGA, than placebo and etanercept over 12 weeks.
In the UNCOVER-1 and -2 trials, 73.8% of patients who were randomised to receive ixekizumab every 4 weeks maintained an sPGA score of 0 or 1 at week 60 compared with 39.0% and 7.0% of those randomised to ixekizumab every 12 weeks and placebo, respectively. High rates for PASI-75, PASI-90 (near complete resolution of plaques) and PASI-100 (complete resolution of plaques) were also maintained or attained during weeks 12 and 60.
During the long-term extension period in the UNCOVER-3 trial, the high rates of response observed during the initial 12 weeks of treatment were generally maintained. Most patients had maintained or attained PASI-90 or PASI-100 responses at week 60.
Nasopharyngitis, upper respiratory tract infections and injection-site reactions were the most commonly reported adverse effects in patients given ixekizumab. Cellulitis, which occurred in three patients, was the most common serious adverse event reported during weeks 0 to 12.