Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

Vitamin D May Be Connected with Health-Related Quality of Life in Psoriasis Patients Treated with Biologics

Suboptimal states of vitamin D may play a role in psoriasis evolution, but the interconnections have been studied over the past years with controversial results. Although a peerless therapy among moderate to severe types of psoriasis, the therapeutic effectiveness of biological therapy may vary unforeseeably between patients and leads to biologics switch. We conducted a pilot study in patients diagnosed with psoriasis and treated with biologics, the purpose of which was to explore the prevalence of suboptimal states of vitamin D, especially in the group of patients characterized by the failure of previous biologics, and to investigate the associations between vitamin D levels and psoriasis, regarding aspects such the severity of the disease and quality of life. Their current result of latent tuberculosis infection (LTBI) was also considered concerning a feasible relationship with vitamin D levels. From July to December 2021, 45 patients corresponding to our inclusion criteria were assessed. Variables such as Psoriasis Area and Severity Index (PASI) score and the Dermatology Life Quality Index (DLQI) score, as well as vitamin D serum concentrations and their LTBI result, were recorded for them. Lower serum concentrations of vitamin D were not more common in patients characterized by failure to previous biologics (p = 0.443), but we concluded a weak correlation between the DLQI score and vitamin D (rho = &minus;0.345, p-value = 0.020), although a statistically insignificant result was obtained between vitamin D and the PASI score (rho = &minus;0.280, p-value = 0.062), and with the LTBI result (rho = &minus;0.053, p-value = 0.728). These results establish a connection between higher levels of vitamin D and a better outcome of psoriasis from the perspective of the patient&rsquo;s quality of life, with no significant association with psoriasis severity and no significant prevalence of suboptimal states among patients that failed previous biologics compared to those with a continuously good response