Safety of Ixekizumab Treatment for up to 5 Years in Adult Patients with Moderate-to-Severe Psoriasis: Results from Greater Than 17,000 Patient-Years of Exposure

Abstract

Introduction: Long-term safety data are critical for evaluating therapies for psoriasis. Ixekizumab has demonstrated efficacy and is well tolerated for the treatment of moderate-to-severe plaque psoriasis. We examined the safety and tolerability of up to 5 years of ixekizumab therapy in patients with psoriasis. Methods: Integrated safety data were analyzed from 13 ixekizumab clinical studies. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for the 12-week induction period in the combined pivotal studies, and for all pooled studies by year(s) of therapy and overall, reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (p-y) and/or frequencies. Results: Total ixekizumab exposure was 17,003.4 p-y (N = 5898); 2749 patients had C 4 years of exposure. When compared across years of exposure, rates for AEs remained largely stable or declined, including TEAEs leading to discontinuation (3.8/100 p-y in year 1, declining to 2.0/100 p-y in year 5); SAEs (range 6.2-7.0/100 p-y); serious infections (range 1.3-1.7/100 p-y); nonmelanoma skin cancer (ranging from 0.5/100 p-y in year 1 to Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.10067021.

Efficacy and Safety of Ixekizumab Through 5 Years in Moderate-to-Severe Psoriasis: Long-Term Results from the UNCOVER-1 and UNCOVER-2 Phase-3 Randomized Controlled Trials

“…Few opportunistic infections were reported (IR: 3.6) using Medical Dictionary for Regulatory Activities terms. Incidence rates of cerebro-cardiovascular events, depression and malignancy were similar to those observed in integrated analyses across 13 clinical trials [47].…”

“…These data comprise all patients in the approved dosing regimen patient population, including those who escalated to every-2-week dosing during the long-term extension period. Adverse events related to discontinuation were arthralgia, ischemic stroke, laryngeal squamous cell carcinoma, maternal exposure during pregnancy, prostate cancer, necrotizing fasciitis and venous thrombosis of the limb b Total patient years = total time patients were in the treatment period approximately 17,000 patient-years across 13 clinical trials in adult patients with psoriasis [23,47]. The SAE IR during year 1 was lower than in subsequent years, which may have been a reflection of the small sample size of this data set.…”

A head‐to‐head comparison of ixekizumab vs. guselkumab in patients with moderate‐to‐severe plaque psoriasis: 12‐week efficacy, safety and speed of response from a randomized, double‐blinded trial

“…By contrast, IXORA‐R was designed to assess eight of the nine primary and major secondary time points in the first 12 weeks of the study, with one major secondary time point (PASI 100 at week 24) remaining to be disclosed after the trial finishes. IXORA‐R did not measure long‐term efficacy and safety because previous trials have demonstrated efficacy and safety of ixekizumab with up to 4 and 5 years of continuous treatment, respectively . The focus on early responses allowed direct comparison of the speed at which improvements in psoriasis occur for patients treated with ixekizumab vs. guselkumab.…”

“…Ixekizumab, a high‐affinity monoclonal antibody that selectively targets IL‐17A, has demonstrated greater and faster skin clearance than etanercept and ustekinumab, with consistent long‐term efficacy, safety and durability of response for up to 5 years of continuous treatment . Here, we report the primary 12‐week results of IXORA‐R, which compared the efficacy, safety and speed of response of ixekizumab vs. guselkumab, an IL‐23p19 inhibitor, in patients with moderate‐to‐severe plaque psoriasis.…”

Treatment strategies in axial spondyloarthritis: what, when and how?

“…Despite promising pre-clinical data in IBD, inhibition of IL-17 with secukinumab and brodalumab was associated with worsening Crohn’s disease [ 66 , 67 ]. Reassuringly, the incidence of new-onset IBD with IL-17A inhibition appears uncommon in axSpA and psoriasis [ 68 , 69 ]. While inhibition of IL-23 appears to be an effective strategy in IBD [ 70 ], this is not effective for axSpA [ 35 , 36 ].…”