Taltz ® (ixekizumab)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information. Please refer to the link for full prescribing information: Taltz Summary of Product Characteristics (SmPC)

Is there any risk for depression and suicide-related adverse events with Taltz® (ixekizumab) treatment?

Analyses of ixekizumab clinical trial data do not show evidence of increased risk of depression or suicide-related events associated with ixekizumab treatment.

UK_cFAQ_IXE025_SUICIDE_RELATED_TEAEs_DEPRESSION_PsO_PsA_axSpA
UK_cFAQ_IXE025_SUICIDE_RELATED_TEAEs_DEPRESSION_PsO_PsA_axSpA
en-GB

Summary

Depression or Suicidal Ideation and Behaviour are not listed as adverse reactions in the Taltz summary of product characteristics.1

There was not any evidence of worsening of depression up to 60 weeks treatment with ixekizumab as assessed by the Quick Inventory of Depressive Symptomatology Self Report.1

Across the psoriasis clinical development program (15 adult and 1 pediatric trials) including data for 6645 patients with 17,902 PY of exposure to ixekizumab as of March 19, 2020

  • depression was reported by 218 (3.3%) patients (IR=1.2 per 100 PY), and
  • there were no completed suicides2 

Across the psoriatic arthritis clinical development program (4 trials) including data for 1401 patients with 2247.7 PY of exposure to ixekizumab as of March 19, 2020

  • depression was reported by 37 (2.6%) patients (IR=1.6 per 100 PY)3
  • suicidal ideation was reported by 1 (0.1%) patient (IR=0.0 per 100 PY), and
  • there were no suicide attempts or completed suicides.2

Across the axial spondyloarthritis clinical development program (AS/r-axSpA and nr-axSpA trials) including data for 932 patients with 1792.2 PY of exposure to ixekizumab as of March 19, 2020

  • depression was reported by 18 (1.9%) patients (IR=1.0 per 100 PY)4
  • suicidal ideation was reported by 2 (0.2%) patients (IR=0.1 per 100 PY)2
  • there was 1 completed suicide (0.1% of total axSpA patient population) in the ixekizumab 80 mg Q2W treatment arm (N=98) in the 16-week double-blind treatment period of the COAST-W trial.5

Neuropsychiatric-Related Exclusion Criteria in Ixekizumab Clinical Trial Programs

Patients with comorbid depression were not excluded from the psoriasis, PsA, or axSpA clinical trials.5-9

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.7-10

Depression and Suicidal Ideation and Behavior in Psoriasis Clinical Trials

Please note that the dosing schedule IXEQ4W during the first 12 weeks of treatment (induction phase) and the dosing schedule IXEQ12W mentioned below are not consistent with the approved dosing schedule for plaque psoriasis. Please refer to the Taltz summary of product characteristics for approved dosing.

Treatment-Emergent Depression in the UNCOVER Clinical Trials

Depression Adverse Events Through Week 12 in Active- and Placebo-Controlled Psoriasis Clinical Trials: UNCOVER-1, -2, and -3, ITT Population lists depression AEs reported in the 12-week induction period of active- and placebo-controlled pooled clinical trials 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 Population2

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 only.

Across the psoriasis clinical development program (15 adult and 1 pediatric trials) including data for 6645 patients with 17,902 PY of exposure to ixekizumab as of March 19, 2020, depression was reported by 218 (3.3%) patients (IR=1.2 per 100 PY).

Suicidal Ideation and Behavior Incidence in the UNCOVER Clinical Trials

Analyses of ixekizumab clinical trial data do not show evidence of increased risk of suicide-related events associated with ixekizumab treatment.2 

Across the entire ixekizumab clinical development program, the incidence of suicidal behavior and ideation events was

  • consistent with the background incidence rates observed in patients with psoriasis, and
  • comparable across ixekizumab, placebo, and etanercept treatment groups.2,11,12

Across the psoriasis clinical development program (15 adult and 1 pediatric trials) as of March 19, 2020 data cutoff date, there were no completed suicides in 17,902 PY of exposure to ixekizumab (N=6645).2 Lilly will continue to evaluate AE data from the ixekizumab-integrated clinical trial database.

Suicide and Self-Injury Preferred Term Adverse Events in Ixekizumab Psoriasis Clinical Trials lists suicidal ideation and self-injurious behavior AEs in the psoriasis clinical trials.

Suicide and Self-Injury Preferred Term Adverse Events in Ixekizumab Psoriasis Clinical Trials2


Induction Dosing Period,
Weeks 0-12
(UNCOVER-1, -2, and -3)

Induction Dosing Period,
Weeks 0-12
(UNCOVER-1, -2, and -3)

Induction Dosing Period,
Weeks 0-12
(UNCOVER-1, -2, and -3)

Induction Dosing Period,
Weeks 0-12
(UNCOVER-1, -2, and -3)

Randomized Withdrawal Period,

Weeks 12-60
(UNCOVER-1 and -2)

Randomized Withdrawal Period,

Weeks 12-60
(UNCOVER-1 and -2)

Randomized Withdrawal Period,

Weeks 12-60
(UNCOVER-1 and -2)

All PsO IXE,
March 2020 DBL
(16 Trials)

Preferred Term

PBO
N=791
n (%)

ETNa
N=739
n (%)

IXE Q2W
N=1161
n (%)

IXE Q4W
N=1167
n (%)

IXE/PBO
N=402
n (%)

IXE/IXE Q4W
N=416
n (%)

IXE/IXE Q12W
N=408
n (%)

All IXE Exposures
N=6645
n (%)

Suicide attempt

0

0

1 (0.1)

1 (0.1)

0

0

1 (0.2)

11 (0.2)

Suicidal ideation

0

1 (0.1)

0

0

0

0

0

6 (0.1)

Intentional overdose

0

0

0

0

0

0

0

1 (0.0)

Intentional self-injury

0

0

0

0

0

0

0

1 (0.0)

Abbreviations: DBL = database lock; ETN = etanercept; IXE = ixekizumab; PBO = placebo; PsO = psoriasis; Q2W = every 2 weeks; Q4W = every 4 weeks; Q12W = every 12 weeks.

aData from UNCOVER-2 and -3 only.

Depression and Suicidal Ideation and Behavior in Psoriatic Arthritis Clinical Trials

Please note that the dosing schedule IXEQ2W mentioned below is not consistent with the approved dosing schedule for psoriatic arthritis. Please refer to the Taltz summary of product characteristics for approved dosing.1

Treatment-Emergent Depression in the SPIRIT Clinical Trials

Depression Adverse Events Through Week 24 in Psoriatic Arthritis Clinical Trials: SPIRIT-P1 and -P2, Safety Population lists depression AEs reported in the 24-week double-blind treatment period of SPIRIT-P1 and -P2.

Depression Adverse Events Through Week 24 in Psoriatic Arthritis Clinical Trials: SPIRIT-P1 and -P2, Safety Population7,13,14

SPIRIT-P1 

SPIRIT-P1 

SPIRIT-P1 

SPIRIT-P1 

SPIRIT-P2 

SPIRIT-P2

SPIRIT-P2


PBO
N=106
n (%)

ADA Q2Wa
N=101
n (%)

IXE Q2W
N=102
n (%)

IXE Q4W
N=107
n (%)

PBO
N=116
n (%)

IXE Q2W
N=123
n (%)

IXE Q4W
N=122
n (%)

Depression 

1 (1.0)

1 (1.0)

2 (1.9)

3 (2.5)

2 (1.6)

2 (1.6)

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.

Across the PsA clinical development program (4 trials) including data for 1401 patients with 2247.7 PY of exposure to ixekizumab as of March 19, 2020, depression was reported by 37 (2.6%) patients (IR=1.6 per 100 PY).3

Suicidal Ideation and Behavior Incidence in the SPIRIT Clinical Trials

Across the PsA clinical development program (4 trials) including data for 1401 patients with 2247.7 PY of exposure to ixekizumab as of March 19, 2020, suicidal ideation was reported by 1 (0.1%) patient (IR=0.0 per 100 PY). There were no suicide attempts or completed suicides.2

Depression and Suicidal Ideation and Behavior in Ankylosing Spondylitis/Radiographic Axial Spondyloarthritis Clinical Trials

Please note that the dosing schedule IXEQ2W mentioned below is not consistent with the approved dosing schedule for axial spondyloarthritis. Please refer to the Taltz summary of product characteristics for approved dosing.1

Treatment-Emergent Depression in the COAST Clinical Trials

Depression Adverse Events Through Week 16 in AS/r-axSpA Clinical Trials: COAST-V and COAST-W, Safety Population lists depression AEs reported in the 16-week double-blind treatment period of COAST-V and COAST-W.

Depression Adverse Events Through Week 16 in AS/r-axSpA Clinical Trials: COAST-V and COAST-W, Safety Population5,8

COAST-V

COAST-V

COAST-V

COAST-V

COAST-W 

COAST-W 

COAST-W 


PBO
N=86
n (%)

ADA Q2Wa
N=90
n (%)

IXE Q2W
N=83
n (%)

IXE Q4W
N=81
n (%)

PBO
N=104
n (%)

IXE Q2W
N=98
n (%)

IXE Q4W
N=114
n (%)

Depression 

1 (1.0)

0

0

5 (4.8)

2 (2.0)

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 52 in COAST-X Trial in nr-axSpA Patients, Safety Population lists depression AEs reported in the 52-week double-blind treatment period of COAST-X.

Depression Adverse Events Through Week 52 in COAST-X Trial in nr-axSpA Patients, Safety Population9

 

PBO
N=104

IXE Q4W
N=96

IXE Q2W
N=102

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 was discontinued due to a TEAE of suicidal ideation after switching to open label ixekizumab.

Across the axSpA clinical development program (AS/r-axSpA and nr-axSpA trials) including data for 932 patients with 1792.2 PY of exposure to ixekizumab as of March 19, 2020, depression was reported by 18 (1.9%) patients (IR=1.0 per 100 PY).4

Suicidal Ideation and Behavior Incidence in the COAST Clinical Trials

Across the axSpA clinical development program (AS/r-axSpA and nr-axSpA trials) including data for 932 patients with 1792.2 PY of exposure to ixekizumab as of March 19, 2020, suicidal ideation was reported by 2 (0.2%) patients (IR=0.1 per 100 PY).2

There was 1 completed suicide (0.1% of total axSpA patient population) in the ixekizumab 80 mg Q2W treatment arm (N=98) in the 16-week double-blind treatment period of the COAST-W trial. This patient had a documented history of depression for about 1 year that was reported as mild at study entry. The blinded principal investigator judged the event as unrelated to the investigational product.5

References

1Taltz [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands

2Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3Sesin C, Gallo G, Gellett AM, et al. Safety of ixekizumab in patients with psoriatic arthritis: an integrated analysis of 4 clinical trials. Poster presented at: European League Against Rheumatism Virtual Congress; June 2-5, 2021.

4Schwartzman S, Sandoval D, Kronbergs A, et al. Long-term safety profile of ixekizumab treatment on patients with axial spondyloarthritis. Poster presented at: American College of Rheumatology/ARP 2020 Annual Scientific Meeting (Virtual); November 5-9, 2020.

5Deodhar 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

6Gordon 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

7Nash 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

8van 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

9Deodhar 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

10Griffiths CEM, Fava M, Miller AH, Russell J, 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

11Olivier 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

12Strober B, Leonardi C, Papp KA, et al. Short- and long-term safety outcomes with ixekizumab from 7 clinical trials in psoriasis: etanercept comparisons and integrated data. J Am Acad Dermatol. 2017;76(3);432-440.e17. http://dx.doi.org/10.1016/j.jaad.2016.09.026

13Mease 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

14Nash 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.

Glossary

AE = adverse event

AS/r-axSpA = ankylosing spondylitis/radiographic axial spondyloarthritis

axSpA = axial spondyloarthritis

IR = incidence rate

Lilly = Eli Lilly and Company

nr-axSpA = nonradiographic axial spondyloarthritis

PsA = psoriatic arthritis

PY = patient-years

QIDS-SR16 = 16-item Quick Inventory of Depressive Symptomatology - Self-Report

Date of Last Review: October 20, 2020


Contact Lilly

Call or Email us

If you want to ask a Medical Information question or you want to report an adverse event or product complaint you can call us or email us at ukmedinfo@lilly.com

Available Mon - Fri, 10am - 4pm, excluding Bank Holidays

Or you can

Chat with Us

Click to Chat is Offline

If you have a question, you can chat online with a Lilly Medical Information professional.

Submit a request