Impact of Ixekizumab Treatment on Depressive Symptoms and Systemic Inflammation in Patients with Moderate-to-Severe Psoriasis: An Integrated Analysis of Three Phase 3 Clinical Studies

Abstract

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.

Burden, predictors and temporal relationships of comorbidities in patients with hidradenitis suppurativa: a hospital‐based cohort study

“…Biological drugs inhibiting the action of IL‐17, i.e. ixekizumab have been associated with statistically significant reductions in depressive symptom scores in patients with moderate‐to‐severe psoriasis …”

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

“…This depression‐like behaviour may be due to the activation of NFκB/p38MAPK pathways. Griffiths et al . showed in patients with moderate‐to‐severe psoriasis and clinical depression treated with ixekizumab, greater improvements in depression symptoms compared to placebo were observed.…”

What Is New about New Antidepressants?

“…In a comparison of intravenous ketamine and placebo in patients with MDD and controls [13], a rapid antidepressant response to ketamine in the depressed patients was accompanied by an equally rapid improvement of connectivity between the salience network and the DMN. Examples of some of the intracellular, interneuronal, and network effects of antidepressants are summarized in Figure 1 [17, 19-31]. …”