Taltz ® (ixekizumab)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information.For current prescribing information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk (England, Scotland, Wales) or www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).

What is the Incidence of Depression with Taltz® (ixekizumab)?

Analyses of ixekizumab clinical trial data do not show evidence of increased risk of depression with ixekizumab treatment.

UK_cFAQ_IXE025_X1_DEPRESSION_TEAEs_PsO_PsA_axSpA
UK_cFAQ_IXE025_X1_DEPRESSION_TEAEs_PsO_PsA_axSpA
en-GB

Treatment-Emergent Depression in the Ixekizumab Clinical Trials

Note that multiple, different dosing regimens, including unapproved doses, are included in this response. Please refer to Taltz summary of product characteristics for full prescribing information. 

Psoriasis Clinical Trials

Psoriasis is associated with an increased risk of depression and suicide-related thoughts and behaviors, with higher severity of psoriasis associated with increased levels of depression.1-5

Depression Adverse Events Through Week 12 in Active- and Placebo-Controlled Psoriasis Clinical Trials: UNCOVER-1, -2, and -3, ITT Population lists depression adverse events (AEs) reported in the 12-week induction period of active- and placebo-controlled pooled clinical trials, such as UNCOVER-1, -2, and -3.

Depression Adverse Events Through Week 12 in Active- and Placebo-Controlled Psoriasis Clinical Trials: UNCOVER-1, -2, and -3, ITT Population6

PBO
(N=791)
n (%) 

ETNa
(N=739)
n (%)

IXE Q4W
(N=1161)
n (%) 

IXE Q2W
(N=1167)
n (%) 

Depression 

4 (0.5) 

3 (0.4)

4 (0.3) 

4 (0.3)

Abbreviations: ETN = etanercept; ITT = intent-to-treat; IXE = ixekizumab; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

aData from UNCOVER-2 and -3 studies only.

An integrated safety analysis was conducted from all exposures of ixekizumab in adult patients with psoriasis (N=6892; 18,025.7 patient-years [PYs] of exposure) across 17 clinical trials with data up to March 19, 2021. Depression was reported in 215 (3.1%) patients (incidence rate [IR] of 1.2 per 100 PYs of exposure).7

Psoriatic Arthritis Clinical Trials

Depression Adverse Events Through Week 24 in Psoriatic Arthritis Clinical Trials: SPIRIT-P1, Safety Population8,9

SPIRIT-P1 

PBO
(N=106)
n (%)

ADA Q2Wa
(N=101)
n (%)

IXE Q2W
(N=102)
n (%)

IXE Q4W
(N=107)
n (%)

Depression 

0 

1 (1.0)

1 (1.0)

2 (1.9)

Abbreviations: ADA = adalimumab; IXE = ixekizumab; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

aAdalimumab represents an active reference arm; the study was not powered to test equivalence or noninferiority of active treatment arms to each other, including adalimumab vs ixekizumab.

Depression Adverse Events Through Week 24 in Psoriatic Arthritis Clinical Trials: SPIRIT-P2, Safety Population9,10

SPIRIT-P2 

PBO
(N=116)
n (%)

IXE Q2W
(N=123)
n (%)

IXE Q4W
(N=122)
n (%)

Depression 

3 (2.5)

2 (1.6)

2 (1.6)

Abbreviations: IXE = ixekizumab; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

Across the psoriatic arthritis (PsA) clinical development program (4 trials) including data for 1401 patients with 2247.7 PY of exposure to ixekizumab as of March 19, 2021, depression was reported by 37 (2.6%) patients (IR=1.6 per 100 PY).11

Axial Spondyloarthritis Clinical Trials

Depression Adverse Events Through Week 16 in AS/r-axSpA Clinical Trials: COAST-V, Safety Population and Depression Adverse Events Through Week 16 in AS/r-axSpA Clinical Trials: COAST-W, Safety Population list depression AEs reported in the 16-week double-blind treatment period of the COAST-V and COAST-W ankylosing spondylitis/radiographic axial spondyloarthritis (AS/r-axSpA) clinical trials.

Depression Adverse Events Through Week 16 in AS/r-axSpA Clinical Trials: COAST-V, Safety Population12

COAST-V

PBO
(N=86)
n (%)

ADA Q2Wa
(N=90)
n (%)

IXE Q2W
(N=83)
n (%)

IXE Q4W
(N=81)
n (%)

Depression 

0 

1 (1.0)

0

0

Abbreviations: ADA = adalimumab; AS/r-axSpA = ankylosing spondylitis/radiographic axial spondyloarthritis; IXE = ixekizumab; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

aAdalimumab represents an active reference arm; the study was not powered to test equivalence or noninferiority of active treatment arms to each other, including adalimumab vs ixekizumab.

Depression Adverse Events Through Week 16 in AS/r-axSpA Clinical Trials: COAST-W, Safety Population13

COAST-W 

PBO
(N=104)
n (%)

IXE Q2W
(N=98)
n (%)

IXE Q4W
(N=114)
n (%)

Depression 

5 (4.8)

2 (2.0)

0

Abbreviations: AS/r-axSpA = ankylosing spondylitis/radiographic axial spondyloarthritis; IXE = ixekizumab; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

Depression Adverse Events Through Week 52 in COAST-X Trial in nr-axSpA Patients, Safety Population  lists depression AEs reported in the 52-week double-blind treatment period of the COAST-X nonradiographic axial spondyloarthritis (nr-axSpA) clinical trial.

Depression Adverse Events Through Week 52 in COAST-X Trial in nr-axSpA Patients, Safety Population6,14 

 

PBO
(N=104)
n (%)

IXE Q4W
(N=96)
n (%)

IXE Q2W
(N=102)
n (%)

Depressiona

0

0

4 (3.9)

Abbreviations: IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; PBO = placebo; TEAE = treatment-emergent adverse event.

aOne patient with preexisting anxiety in the IXE Q2W arm discontinued study drug due to a TEAE of suicidal ideation after switching to open-label ixekizumab.

Across the axial spondyloarthritis (axSpA) clinical development program (AS/r-axSpA and nr-axSpA trials) including data for 932 patients with 2096.2 PY of exposure to ixekizumab as of March 19, 2021, depression was reported by 19 (2.0%) patients (IR=0.9 per 100 PY).11

Neuropsychiatric-Related Exclusion Criteria in Ixekizumab Clinical Trial Programs

Patients with comorbid depression were not excluded from the psoriasis, PsA, or axSpA clinical trials.10,12-15

Patients were excluded from the ixekizumab clinical trial programs if they had 

  • a score of 3 on Item 12 (thoughts of death or suicide) of the QIDS-SR16
  • a history of suicide attempt (limited to recent history within 30 days of screening or any time between screening and baseline in axSpA trials)
  • presence of an uncontrolled neuropsychiatric disorder, or
  • been clinically judged by the investigator to be at risk for suicide.10,12,14,16

A total of 8 patients of the 5101 screened (0.2%) were excluded for meeting at least 1 neuropsychiatric-related exclusion criterion in the UNCOVER psoriasis trials.6 

In the SPIRIT PsA trials, 5 patients of the 1704 screened (0.3%) were excluded based on QIDS-SR16 exclusion criterion.6

In the COAST-V and COAST-W AS/r-axSpA trials, 2 patients of the 671 screened (0.3%) were excluded based on QIDS-SR16 exclusion criterion.6

In the COAST-X nr-axSpA trial, 1 patient of the 436 screened (0.2%) was excluded based on QIDS-SR16 exclusion criteria.6

References

1Gelfand JM, Troxel AB, Lewis JD, et al. The risk of mortality in patients with psoriasis: results from a population-based study. Arch Dermatol. 2007;143(12):1493-1499. http://dx.doi.org/10.1001/archderm.143.12.1493

2Olivier C, Robert PD, Daihung D, et al. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol. 2010;146(8):891-895. http://dx.doi.org/10.1001/archdermatol.2010.186

3Yeung H, Takeshita J, Mehta NN, et al. Psoriasis severity and the prevalence of major medical comorbidity: a population-based study. JAMA Dermatol. 2013;149(10):1173-1179. http://dx.doi.org/10.1001/jamadermatol.2013.5015

4Armstrong A, Robertson A, Edson-Heredia E, et al. Association of psoriasis severity with health-related quality of life, depression, and work productivity. Poster presented at: 73rd Annual Meeting of the American Academy of Dermatology; March 20-24, 2015; San Francisco, CA.

5Griffiths C, Fava M, Miller A, et al. Impact of ixekizumab treatment on depressive symptoms: an integrated analysis of three phase 3 clinical studies in patients with moderate-to-severe psoriasis. Poster presented at: 74th Annual Meeting of the American Academy of Dermatology; March 4-8, 2016; Washington, DC.

6Data on file, Eli Lilly and Company and/or one of its subsidiaries.

7Griffiths CEM, Gooderham M, Colombel JF, et al. Safety of ixekizumab in adult patients with moderate-to-severe psoriasis: data from 17 clinical trials with over 18,000 patient-years of exposure. Poster presented at: Annual Meeting of the American Academy of Dermatology (AAD); March 25-29, 2022; Boston, MA.

8Mease PJ, van der Heijde D, Ritchlin CT, et al; SPIRIT-P1 Study Group. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76(1):79-87. http://dx.doi.org/10.1136/annrheumdis-2016-209709

9Nash P, Kirkham B, Okada M, et al. A Phase 3 study of the efficacy and safety of ixekizumab in patients with active psoriatic arthritis and inadequate response to tumour necrosis factor inhibitor(s). Poster presented at: 2017 European League Against Rheumatism; June 14-17, 2017; Madrid, Spain.

10Nash P, Kirkham B, Okada M, et al; SPIRIT-P2 Study Group. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet. 2017;389(10086):2317-2327. http://dx.doi.org/10.1016/S0140-6736(17)31429-0

11Schwartzman S, Deodhar A, Combe B, et al. Safety profile of ixekizumab for the treatment of psoriatic arthritis and axial spondyloarthritis up to 3 years: an updated integrated safety analysis. Poster presented at: Annual Meeting of the America College of Rheumatology (ACR Convergence Virtual); November 1-10, 2021.

12van der Heijde D, Cheng-Chung Wei J, Dougados M, et al; COAST-V Study Group. Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial. Lancet. 2018;392(10163):2441-2451. http://dx.doi.org/10.1016/s0140-6736(18)31946-9

13Deodhar A, Poddubnyy D, Pacheco-Tena C, et al; COAST-W Study Group. Efficacy and safety of ixekizumab in the treatment of radiographic axial spondyloarthritis: sixteen-week results from a phase III randomized, double-blind, placebo-controlled trial in patients with prior inadequate response to or intolerance of tumor necrosis factor inhibitors. Arthritis Rheumatol. 2019;71(4):599-611. http://dx.doi.org/10.1002/art.40753

14Deodhar A, van der Heijde D, Gensler LS, et al; COAST-X Study Group. Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial. Lancet. 2020;395(10217):53-64. http://dx.doi.org/10.1016/S0140-6736(19)32971-X

15Gordon KB, Blauvelt A, Papp KA, et al; UNCOVER-1, UNCOVER-2, and UNCOVER-3 Study Groups. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375(4):345-356. http://dx.doi.org/10.1056/NEJMoa1512711

16Griffiths CEM, Fava M, Miller AH, et al. 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. Psychother Psychosom. 2017;86(5):260-267. http://dx.doi.org/10.1159/000479163

Date of Last Review: 04 April 2022


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