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 cardiovascular events? Can it be used in patients with coexisting cardiovascular disease?

The use of ixekizumab in patients with cardiovascular disease has not been studied. In clinical trials, major adverse cardiac events were uncommon.

General Information

The Summary of Product Characteristics for ixekizumab does not contain any contraindication, warnings or precautions, or other language involving the use of ixekizumab in patients with cardiovascular comorbidities.1

  • The use of ixekizumab specifically in patients with CV comorbidities has not been studied. 

  • Patients with preexisting CV disorders were permitted to enroll in the studies and continue their medications as long as their condition and medication doses were stable.2-4

  • Ixekizumab exposure has not been associated with an increased risk of MACE in psoriasis, PsA, or axSpA clinical trials.5-9

  • Investigators have concluded that ixekizumab use is not associated with clinically meaningful changes in glucose, total cholesterol, LDL, HDL, VLDL, TG, and LDL/HDL ratio in patients with moderate-to-severe plaque psoriasis.10

Major Adverse Cerebro-cardiovascular Events

Clinical Trials in Moderate-to-Severe Psoriasis

In an integrated analysis of the UNCOVER clinical trial data, MACE were uncommon, balanced across treatment groups, and exposure-adjusted incidence rates per 100 PY remained stable over time.10

For the analyses described in this medical response, MACE was defined as a composite endpoint for

  • nonfatal MI

  • nonfatal stroke, and

  • CV death.11

Total MACE incidence and EAIRs integrated across all ixekizumab psoriasis exposures as of March 21, 2019 are available in Table 1.

Table 1. Incidence of Major Adverse Cerebrocardiovascular Events in Ixekizumab-Treated Psoriasis Patients11,12

 

All IXE-Treated Patients
N=6091
PY=17,499.3
a

Total Adjudicated MACE, n (%) [IR]

85b (1.5) [0.5]

Vascular death [IR]

20 [0.1]

Nonfatal MI [IR]

45 [0.3]

Nonfatal stroke [IR]

21 [0.1]

Abbreviations: IR = incidence rate (per 100 patient-years); IXE = ixekizumab; MACE = major adverse cardiac events; MI = myocardial infarction; PY = patient-years.

a Data as of March 21, 2019.

b One patient experienced nonfatal stroke and vascular death.

Clinical Trials in Psoriatic Arthritis

For the analyses described in this medical response, MACE was defined as a composite endpoint for

  • nonfatal MI

  • nonfatal stroke, and

  • CV death.11

Total MACE incidence and EAIRs integrated across all ixekizumab PsA exposures as of March 21, 2019 is available in Table 2.

Table 2. Incidence of Major Adverse Cerebrocardiovascular Events in Ixekizumab-Treated Psoriatic Arthritis Patients11,12

 

All IXE-Treated Patients
N=1401
PY=2228.6
a

Total Adjudicated MACE, n (%) [IR]

12 (0.9) [0.5]

Vascular death [IR]

2 (0.1) [0.1]

Nonfatal MI [IR]

6 (0.4) [0.3]

Nonfatal stroke [IR]

4 (0.3) [0.2]

Abbreviations: IR = incidence rate (per 100 patient-years); IXE = ixekizumab; MACE = major adverse cardiac events; MI = myocardial infarction; PY = patient-years.

a Data as of March 21, 2019.

Rates of MACE were similar in psoriasis and PsA clinical trials. There was no pattern of increased risk of MACE with longer exposures to ixekizumab, and rates of MACE were consistent with the overall background rates among patients with PsA.11,12

There is no evidence that treatment with ixekizumab in patients with PsA modifies the underlying risk for adverse cerebro-cardiovascular events such as MI or stroke.11

Clinical Trials in Axial Spondyloarthritis

There were no MACE reported in COAST-V and COAST-W in patients with AS/r-axSpA through the 16-week double-blinded treatment periods.7,8

In the COAST-V trial (N=341), an AE of aphasia, later adjudicated as a TIA, occurred in 1 patient in the ixekizumab 80 mg Q4W cohort.11

In the COAST-W trial (N=316), an AE of stent placement and atrial fibrillation occurred in 1 patient each in the placebo and ixekizumab 80 mg Q2W cohorts, respectively.11

In the COAST-X trial in patients with nr-axSpA, there were no MACE events reported during the 52-week double-blinded treatment period prior to rescue with ixekizumab 80 mg Q2W.11

In the COAST-X trial (N=302), an AE of ventricular arrhythmia (MedDRA preferred term extrasystoles) occurred in 1 patient in the ixekizumab 80 mg Q2W treatment group.11

Total MACE incidence and EAIRs integrated across 4 ixekizumab axSpA trials (including AS/r-axSpA and nr-axSpA patients) exposures  (N=929) as of April 2019 is available in Table 3.

Table 3. Incidence of Major Adverse Cerebro-Cardiovascular Events in Ixekizumab-Treated Axial Spondyloarthritis Patients11


All IXE-Treated Patients 
N=929
PY=1336.2

Total adjudicated MACE, n (%) [IR]

2 (0.2) [0.1]

Vascular death [IR]

0

Nonfatal MI [IR]

2 (0.2) [0.1]

Nonfatal stroke [IR]

0

Abbreviations: IXE = ixekizumab; MACE = major adverse cerebro-cardiovascular events; MI = myocardial infarction; IR = incidence rate; PY = patient-years.

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. 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

4. 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

5. Mease P, Roussou E, Burmester GR, et al. Safety of ixekizumab in patients with psoriatic arthritis: results from a pooled analysis of three clinical trials. Arthritis Care Res (Hoboken). 2019;71(3):367-378. http://dx.doi.org/doi:10.1002/acr.23738

6. Papp K, Bissonette R, Ohtsuki M, et al. Ixekizumab shows no association with major adverse cardiac events (MACE) in patients with moderate-to-severe psoriasis: an integrated safety analysis of clinical trials. Poster presented at: 74th Annual Meeting of the American Academy of Dermatology; March 4-8, 2016; Washington, DC. https://www.aad.org/eposters/Submissions/getFile.aspx?id=3413&type=sub

7. 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

8. 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

9. 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

10. Wu JJ, Egeberg A, Solomon JA, et al. Ixekizumab treatment shows a neutral impact on the glucose and lipid profile of patients with moderate-to-severe psoriasis: results from UNCOVER-1, -2, and -3. Poster presented at: 75th Annual Meeting of the American Academy of Dermatology; March 3-7, 2017; Orlando, FL. https://www.aad.org/eposters/Submissions/getFile.aspx?id=4662&type=sub

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

12. 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.

Glossary

AE = adverse event

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

axSpA = axial spondyloarthritis

CV = Cardiovascular

EAIR = exposure adjusted incidence rate

HDL = high density lipoprotein

LDL = Low density lipoprotein

MACE - major adverse cardiovascular events

MI = myocardial infarction

nr-axSpA = nonradiographic axial spondyloarthritis

PsA = psoriatic arthritis

PY = patient-years

Q2W = every 2 weeks

Q4W = every 4 weeks

TG = triglycerides

TIA = transient ischemic attack

VLDL (-C) = very low density lipoprotein cholesterol

VLDL = very low density lipoprotein

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: March 18, 2020

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