SummaryIn this article by Gordon et al, 60-week data from the UNCOVER-1, 2, and 3 trials of the ixekizumab phase 3 program, and 12-week data from UNCOVER-1, are reported (12-week data from UNCOVER-2 and 3 have previously been presented1 ). Results from the placebo-controlled phase of UNCOVER-3 were consistent with those of UNCOVER-1 and 2. In the 2-weekly dosing group, 81.8% and 89.1% of patients achieved the co-primary endpoints of sPGA (static Physicians Global Assessment) score of 0/1 and PASI (Psoriasis Area Severity Index) 75 response, respectively, while 76.4% and 82.6% achieved these endpoints in the 4-weekly dosing group, and 3.2% and 3.9% in the in the placebo group (P<0.001).
At week 12 in UNCOVER-1 and 2, only patients who had an sPGA 0/1 response to ixekizumab continued into the long-term extension (LTE) period where they entered a randomized withdrawal period and were assigned to two dosing regimens of ixekizumab or placebo. If a patient achieved an sPGA 3 response at any stage between weeks 12 and 60, they were classified as a non-responder, regardless of their response at week 60. Despite these stringent criteria, 74% of patients receiving the currently approved maintenance dose of ixekizumab maintained an sPGA score of 0/1 compared with 7.0% of placebo-treated patients. In the UNCOVER-3 trial, all patients could enter the LTE period, where they received 80 mg of ixekizumab every 4 weeks until week 60, serving as a continuously treated cohort; 73% and 80% of patients who received continuous treatment of ixekizumab from week 0 to 60, achieved an sPGA 0/1 or PASI 75 response, respectively. Eleven patients reported inflammatory bowel disease (IBD) while receiving ixekizumab, with an additional 3 cases reported in patients receiving placebo during the randomized withdrawal period. The rate of cardiovascular events did not differ between ixekizumab and placebo-treated patients, but there were 22 (0.6%) cardiovascular events and two cardiovascular deaths throughout the 60 weeks. The rates of candida infection were significantly higher in ixekizumabtreated patients, the majority of which were mild.