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
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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-SR 16) 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-SR 16 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-SR 16 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.
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In those trials, 45% of patients treated with ixekizumab remitted compared with 18% on placebo.
“Moreover, 45% of patients treated with ixekizumab remitted compared to 18% on placebo.”
From Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories (2023) · cites this paper as [175]
The improvement in depressive symptoms correlated with reductions in CRP and the psoriasis area index.
“The improvement in depressive symptoms correlated with reductions in CRP and the psoriasis area index (175).”
From Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories (2023) · cites this paper as [175]
In 3 randomized, double-blind, controlled trials in patients with moderate-to-severe plaque psoriasis, ixekizumab, an anti-IL-17 antibody, reduced QIDS-SR-16 scores and improved depression at week 12.
“A study analyzing the efficacy of 3 randomized, double-blind, controlled trials in patients with moderate-to-severe plaque psoriasis, found that ixekizumab, an anti-IL-17 antibody, reduced scores on the QIDS-SR-16 and improved depression at week 12.”
From Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories (2023) · cites this paper as [175]
A targeted anti-IL-17A approach using Ixekizumab has shown promise in reducing depressive symptoms in 40% of psoriasis patients with co-occurring MDD.
“A targeted anti-IL-17A approach using Ixekizumab has shown promise in reducing depressive symptoms in 40% of psoriasis patients with co-occurring MDD”
From Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress (2025) · cites this paper as [64]
Anti-IL-17A therapy induces remission of depression in 40% of psoriasis patients experiencing moderately severe depression.
“anti-IL-17A therapy induces remission of depression in 40% of psoriasis patients experiencing moderately severe depression (Griffiths et al., 2017).”
From Distinct characteristics of hippocampal pathogenic th17 cells in a mouse model of depression (2018) · cites this paper as Griffiths et al., 2017
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References 20 · Cited by 115
- Authors
- Griffiths, C. E. M., Fava, M., Miller, A. H., Russell, J., Ball, S. G., Xu, W., Acharya, N., & Rapaport, M. H.
- Affiliations
- Manchester Academic Health Science Centre (GB)
- Emory University (US)
- Oregon Health & Science University (US)
- Eli Lilly (United States) (US)
- Venue
- Psychotherapy and Psychosomatics
- Publisher
- S. Karger AG
- Published
- 2017
- Volume
- 86
- Issue
- 5
- Pages
- 260-267
- ISSN
- 0033-3190 (ISSN-L)
- 1423-0348
- OpenAlex
- W2754104556
- Cited by
- 115
- References
- 20
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 12 · 2023: 15 · 2022: 15 · 2021: 16 · 2020: 14 · 2019: 8 · 2018: 11
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Psychotherapy and Psychosomatics (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by-nc-nd)
- Funders
- Eli Lilly and Company
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Rheumatology › Spondyloarthritis Studies and Treatments
- Keywords
- ixekizumab, psoriasis, depressive symptoms, comorbid depression, systemic inflammation, C-reactive protein, IL-17A, anti-IL-17A therapy, etanercept, QIDS-SR16, PASI, depression remission
- MeSH terms
- Etanercept, Anti-Inflammatory Agents, Non-Steroidal, Depression, Dermatologic Agents, Double-Blind Method, Female, Humans, Inflammation, Male, Middle Aged, Psoriasis, Severity of Illness Index, Treatment Outcome, Antibodies, Monoclonal, Humanized
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