Long-term safety profile of ixekizumab in patients with moderate-to-severe plaque psoriasis: an integrated analysis from 11 clinical trials.

BACKGROUND: Psoriasis in many patients is a chronic and recalcitrant disease that requires long-term treatment, reinforcing the importance of long-term safety data. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, is approved for treating patients with moderate-to-severe plaque psoriasis. OBJECTIVE: To determine long-term safety of ixekizumab in psoriasis. METHODS: Integrated safety data are presented from 12-week induction period, 12-60-week maintenance period, and from all ixekizumab-treated patients from 11 clinical studies. Exposure-adjusted incidence rates (IRs) per 100 patient-years are reported. RESULTS: Overall, 5689 patients accounted for 12 061.5 patient-years of ixekizumab exposure from 11 studies. Over 156 weeks, a total of 83.9% (n = 4775) of patients reported treatment-emergent adverse events (AEs). Most opportunistic infections (IR [95% confidence interval; CI] 1.8 [1.6, 2.1]) reported were mucocutaneous candidiasis. The IR (95% CI) for oral Candida infection was 0.9 (0.8, 1.1). There was no trend of increase in IR of AEs of special interest. Serious AEs were reported in 11.8% of patients; death occurred in 0.4% (n = 23) of patients. CONCLUSION: The 3-year, long-term maintenance treatment with ixekizumab did not show any new safety signals in patients with moderate-to-severe plaque psoriasis.

Phase 3, open-label, randomized study of the pharmacokinetics, efficacy and safety of ixekizumab following subcutaneous administration using a prefilled syringe or an autoinjector in patients with moderate-to-severe plaque psoriasis (UNCOVER-A).

BACKGROUND: The efficacy of ixekizumab, an anti-interleukin-17A (anti-IL-17A) monoclonal IgG4 antibody, was demonstrated in moderate-to-severe psoriasis patients when administered via prefilled syringe (PFS). OBJECTIVE: To evaluate the effect of two drug delivery devices on the pharmacokinetics (PK) of ixekizumab as well as efficacy and safety with both devices. METHODS: In the first 12 weeks of an open-label, phase 3 study, moderate-to-severe psoriasis patients were randomized to ixekizumab delivery via PFS or autoinjector device. Randomization was stratified by weight (<80 kg, 80-100 kg, >100 kg), injection assistance (yes/no) and injection site (arm, thigh or abdomen). Following a 160-mg initial dose at week 0, patients received subcutaneous 80-mg ixekizumab as a single injection every 2 weeks for 12 weeks. Blood samples were collected following the initial 160-mg dose on days 2, 4, 7, 10 and 14 for PK analysis. Primary PK parameters were maximum concentration (Cmax ) and area under the curve (AUC0-tlast ) where tlast is the time of last sample (14 days ± 24 h). Efficacy was assessed by percent improvement on the Psoriasis Area and Severity Index (PASI) at week 12. Adverse event reporting, vital signs and clinical laboratory data were used to evaluate safety. RESULTS: Of 204 randomized patients, 192 were included in the PK analysis (PFS: 94; autoinjector: 98). The PFS and autoinjector showed similar geometric mean Cmax (90% CI) [15.0 µg/mL (13.9-16.1) vs. 14.8 µg/mL (13.8-15.9)] and geometric mean AUC0-tlast (90% CI) [157 µg × day/mL (147-168) vs. 154 µg × day/mL (144-165)]. When comparing Cmax and AUC0-tlast of the autoinjector to PFS, the geometric LS mean ratios were 0.97. At week 12, mean percent PASI improvement (via modified baseline observation carried forward) was similar with the PFS (89.3%) and autoinjector (86.9%). Both devices had safety results that were consistent with the known safety profile of ixekizumab. CONCLUSION: The PK, efficacy and safety of ixekizumab administered subcutaneously by PFS and autoinjector were similar. Clinicaltrials.gov number: NCT01777191 https://clinicaltrials.gov/ct2/show/NCT01777191.