Olanzapine was effective in the treatment of bipolar mania in adolescent patients. Patients treated with olanzapine, however, had significantly greater weight gain and increases in the levels of hepatic enzymes, prolactin, fasting glucose, fasting total cholesterol, and uric acid.

Ixekizumab had an acceptable safety profile with no unexpected safety findings during ixekizumab maintenance in psoriasis.

Summary Background Plaque psoriasis affects children and adults, but treatment options for paediatric psoriasis are limited. Objectives To evaluate the efficacy and safety of ixekizumab (IXE), a high‐affinity monoclonal antibody that selectively targets interleukin‐17A, for moderate‐to‐severe paediatric psoriasis. Methods In a randomized, double‐blind, placebo‐controlled, phase III study (IXORA‐PEDS), patients aged 6 to < 18 years with moderate‐to‐severe plaque psoriasis were randomized 2 : 1 to weight‐based dosing of IXE every 4 weeks (IXE Q4W, n = 115) or placebo (n = 56) through week 12, followed by open‐label IXE Q4W. Coprimary endpoints were the proportions of patients at week 12 achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and those achieving a static Physician's Global Assessment score of 0 or 1 (sPGA 0,1). Results IXE was superior (P < 0·001) to placebo for both coprimary endpoints of PASI 75 (IXE Q4W, 89%; placebo, 25%) and sPGA (0,1) (IXE Q4W, 81%; placebo, 11%). IXE was also superior for all gated secondary endpoints, including PASI 75 and sPGA (0,1) at week 4, improvement in itch, and complete skin clearance. IXE Q4W provided significant (P < 0·001) improvements vs. placebo in quality of life and clearance of scalp and genital psoriasis. Responses at week 12 were sustained or further improved through week 48. Through week 12, 45% (placebo) and 56% (IXE) of patients reported treatment‐emergent adverse events. One serious adverse event was reported (IXE), one patient discontinued due to an adverse event (placebo) and no deaths were reported. Conclusions IXE was superior to placebo in the treatment of moderate‐to‐severe paediatric psoriasis, and the safety profile was generally consistent with that observed in adults. What is already known about this topic? Paediatric psoriasis affects approximately 1% of children and can negatively impact health‐related quality of life. Treatment options for paediatric psoriasis are typically limited to off‐label treatments and approved systemic biologics. Ixekizumab, a high‐affinity monoclonal antibody that selectively targets interleukin‐17A, is approved for moderate‐to‐severe plaque psoriasis in adults and was recently approved by the US Food and Drug Administration for moderate‐to‐severe paediatric psoriasis. What does this study add? Ixekizumab resulted in rapid and statistically significant improvements over placebo in skin involvement, itch and health‐related quality of life, which persisted through 48 weeks of treatment in paediatric patients with moderate‐to‐severe plaque psoriasis. The safety profile of ixekizumab was generally consistent with that seen in adults. Ixekizumab may be an additional potential therapeutic option and an additional class of biologic therapy (interleukin‐17A antagonist) for the treatment of moderate‐to‐severe paediatric psoriasis. Plain language summary available online

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Background: Depression is a common comorbidity in psoriasis, and both conditions are associated with systemic inflammation. The efficacy of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, was evaluated in patients with moderate-to-severe plaque psoriasis (psoriasis) and depressive symptoms that were at least moderately severe. Methods: Data were integrated from 3 randomized, double-blind, controlled phase 3 trials. At baseline and week 12, depressive symptoms and inflammation were assessed by the 16-item Quick Inventory of Depressive Symptomology - Self-Report (QIDS-SR₁₆) and by a high-sensitivity assay of serum C-reactive protein (hsCRP), respectively. A subgroup of patients with at least moderately severe depressive symptoms at baseline (QIDS-SR₁₆ total score ≥11) was analyzed. Improvement in psoriasis was assessed by the Psoriasis Area and Severity Index (PASI). Results: Approximately 10% of the overall psoriasis population had at least moderately severe depressive symptoms at baseline. At week 12, comorbid patients treated with ixekizumab had significantly greater improvements in their QIDS-SR₁₆ total score (ixekizumab 80 mg every 2 weeks [Q2W], -7.1; ixekizumab 80 mg every 4 weeks [Q4W], -6.1) vs. placebo (-3.4) (p < 0.001, both comparisons) and higher rates of remission of depressive symptoms (ixekizumab Q2W, 45.2%; ixekizumab Q4W, 33.6%) vs. placebo (17.8%) (p ≤ 0.01, both comparisons). Patients treated with ixekizumab also had significant reductions in hsCRP and PASI compared to placebo. Etanercept treatment was not associated with significant improvements in depressive symptoms compared to placebo. Conclusions: In this comorbid population, 12 weeks of ixekizumab therapy resulted in remission of depression for approximately 40% of patients and improved systemic inflammation as indicated by hsCRP.

The 3-year, long-term maintenance treatment with ixekizumab did not show any new safety signals in patients with moderate-to-severe plaque psoriasis.

Objectives The aim of this integrated analysis is to evaluate the long-term safety and tolerability of ixekizumab in adults with psoriasis, PsA and axial SpA. Methods Integrated safety data from 21 clinical trials are presented by indication in patients who received at least one dose of ixekizumab. Adverse events (AEs) and treatment-emergent adverse events (TEAEs) adjusted incidence rates (IRs) per 100 patient-years (PY) up to 5 years’ exposure are reported. Results A total of 8228 patients with an ixekizumab exposure of 20 895.9 PY were included in this analysis. The most common TEAEs were nasopharyngitis, upper respiratory tract infection and injection-site reactions. Across populations, IRs were low for AEs leading to discontinuation (IRs ≤5.1 per 100 PY), serious AEs (IRs ≤6.0 per 100 PY) and death (IRs ≤0.3 per 100 PY). The most reported TEAEs of special interest were infections (IRs ≤35.8 per 100 PY). Patients rarely reported malignancies (IR ≤0.8), IBD including ulcerative colitis and Crohn’s disease (IR ≤0.8) and major adverse cardiovascular events (IR ≤0.5). TEAEs were most commonly reported the first 2 years of exposure with ixekizumab and IR decreased over the years (infections, injection-site reactions and depression) or remained constant over the entire treatment period (serious infections, major adverse cardiovascular events, malignancies and IBD). Conclusion This long-term analysis on the safety of ixekizumab was consistent with previously published reports and did not show any new safety signals. The safety profile and tolerability reported in this integrated analysis remained consistent with the known safety profile for ixekizumab.

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.