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)

Taltz® ▼ (ixekizumab): Is there any risk for depression and suicide-related adverse events with 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.

Ixekizumab Label Information

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

Neuropsychiatric-Related Exclusion Criteria in Ixekizumab Clinical Trial Programs

Patients with comorbid depression were not excluded from the psoriasis, PsA, or axSpA clinical trials.2-6

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.3,4,6,7

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. 1

Treatment-Emergent Depression in the UNCOVER Clinical Trials

Depression AEs reported in the 12-week induction period of active- and placebo-controlled pooled clinical trials UNCOVER-1, -2, and -3 are listed in Table 1

Table 1. Depression AEs Through Week 12 in Active- and Placebo-Controlled Psoriasis Clinical Trials: UNCOVER-1, -2, and -3, ITT Population8


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: AE = adverse event; ETN = etanercept; ITT: Intent to Treat; IXE = ixekizumab; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

a Data from UNCOVER-2 and -3 only.

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.8 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.8-10

Across the psoriasis clinical development program (14 trials) as of March 21, 2019 data cutoff date, there were no completed suicides in 17,499.3 PY of exposure to ixekizumab (N=6091).11 Lilly will continue to evaluate AE data from the ixekizumab integrated clinical trial database.

Suicidal ideation and self-injurious behavior AEs are listed in Table 2.

Table 2. Suicide and Self-Injury Preferred Term Adverse Events in Ixekizumab Psoriasis Clinical Trials8


Induction Dosing Perioda

Induction Dosing Period a

Induction Dosing Period a

Induction Dosing Period a

Randomized Withdrawal Periodb

Randomized Withdrawal Period b

Randomized Withdrawal Period b

All PsO IXE,
Mar 2019 DBL
(14 trials)


PBO
N= 791
n (%)

ETNc
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=6091
n (%)

Preferred term





 




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

5 (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.

a Week 0-12 (UNCOVER-1, -2, -3)

b Week 12-60 (UNCOVER-1 and -2)

c Data 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 AEs reported in the 24-week double-blind treatment period of SPIRIT-P1 and -P2 are listed in Table 3.

Table 3. Depression AEs Through Week 24 in Psoriatic Arthritis Clinical Trials: SPIRIT-P1 and -P2, Safety Population3,12,13










SPIRIT-P1 

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; AE = adverse event; IXE = ixekizumab; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

a Adalimumab 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.

Suicidal Ideation and Behavior Incidence in the SPIRIT Clinical Trials

Across the PsA clinical development program (4 trials) including data for 1401 patients with 2228.6 PY of exposure to ixekizumab as of March 2019, suicidal behavior/self-injury was reported by 1 patient.14 There were no completed suicides.11

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 AEs reported in the 16-week double-blind treatment period of COAST-V and COAST-W are listed in Table 4.

Table 4. Depression AEs Through Week 16 in AS/r-axSpA Clinical Trials: COAST-V and COAST-W, Safety Population4,5










COAST-V

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; AE = adverse event; IXE = ixekizumab; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

a Adalimumab 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.

Suicidal Ideation and Behavior Incidence in the COAST Clinical Trials

Of 929 patients (1336.2 PY) exposed to ixekizumab in the axSpA clinical development program (including AS/r-axSpA and nr-axSpA trials) with data through March 2019, 2 (0.2% [IR=0.1 per 100 PYs) patients reported suicidal behavior/self-injury.14 There was 1 completed suicide (1.0%) 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

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

2. Gordon KB, Blauvelt A, Papp KA, et al. 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

3. Nash P, Kirkham B, Okada M, et al. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomized, 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

4. van der Heijde D, Cheng-Chung Wei J, Dougados M, et al. 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

5. Deodhar A, Poddubnyy D, Pacheco-Tena C, et al. 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

6. Deodhar A, van der Heijde D, Gensler LS, et al. 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

7. Griffiths 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

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

9. Olivier 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

10. Strober 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

11. Genovese MC, Kameda H, Rahman P, et al. Safety profile of ixekizumab in patients with moderate-to-severe plaque psoriasis and psoriatic arthritis: integrated analysis of 18 clinical trials. Poster presented at: American College of Rheumatology/ARP; November 8-13, 2019; Atlanta, GA.

12. Mease PJ, van der Heijde D, Ritchlin CT, et al. 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

13. Nash 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.

14. Genovese MC, Mysler E, Tomita T, et al. Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials. Rheumatology (Oxford). Published online May 25, 2020. https://doi.org/10.1093/rheumatology/keaa189

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 = Quick Inventory of Depressive Symptomatology-Self Report (16 items)

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Date of Last Review: July 20, 2020


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