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).

Taltz® (ixekizumab): Can it be used in patients with hepatic impairment? Is a dose adjustment recommended?

Ixekizumab has not been studied in patients with hepatic impairment. No dose recommendations can be made. Hepatic safety data for each indication is provided.

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UK_cFAQ_IXE340_HEPATIC_IMPAIRMENT_PsO_PsA_axSpA
en-GB

Ixekizumab Label Information Related to Hepatic Impairment

Specific clinical pharmacology studies to evaluate the effects of renal impairment and hepatic impairment on the PK of ixekizumab have not been conducted.

  • Renal elimination of intact ixekizumab, an IgG MAb, is expected to be low and of minor importance;
  • similarly, IgG MAbs are mainly eliminated via intracellular catabolism and hepatic impairment is not expected to influence clearance of ixekizumab.1

Ixekizumab has not been studied in patients with renal or hepatic impairment. No dose recommendations can be made.1

Please refer to Taltz summary of product characteristics for full prescribing information.

Clinical Trial Data

Study exclusion criteria for all clinical trials included

  • having a hepatic disorder that, in the opinion of the investigator, poses an unacceptable risk to the patient if participating in the study or of interfering with the interpretation of data,
  • or having aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels more than 2.5 times the upper limit of normal (ULN).2-6

Brief descriptions of the pivotal clinical trials for moderate-to-severe psoriasis, active psoriatic arthritis, and active axial spondyloarthritis (axSpA) are provided at the end of this response.

Note that data from multiple, different dosing regimens, including unapproved doses, are included in this response.

Psoriasis

An integrated analysis of the phase 3 clinical trials demonstrated no significant differences between ixekizumab treatment groups and placebo, during either the 12-week induction or 48-week maintenance periods, in the proportions of patients with treatment-emergent elevations in

  • ALT or AST ≥3 times ULN, 5 times ULN, and 10 times ULN, or
  • alkaline phosphatase >2 times ULN.6

The percentages of patients reporting hepatic-related AEs were similar across the treatment groups in the induction and maintenance periods.6

Overall there were no clinically important changes from baseline in mean liver biochemical test results (ALT, AST, total bilirubin, alkaline phosphatase) in any treatment group in ixekizumab patients compared to placebo or etanercept patients in the 12-week induction period of the active-controlled pivotal trials UNCOVER-2 and UNCOVER-3.5 In the PsO population, longer term exposure with ixekizumab is not associated with an increase in clinically important hepatic-related laboratory changes or with an increased risk of hepatic-related AEs.6

Across 17 pooled psoriasis trials in adult patients (N=6892), accounting for 18,025.7 patient-years (PYs) of total ixekizumab exposure as of the March 19, 2021 database lock,

  • increased ALT was reported in 122 patients (1.8%) with incidence rate (IR) 0.7 per 100 PYs and
  • increased AST was reported in 83 patients (1.2) with IR 0.5 per 100 PYs.6

These treatment-emergent adverse events (TEAEs) are based on the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs) "alanine aminotransferase increased" and "aspartate aminotransferase increased."

Reports of Increased AST and ALT During 12-Week Placebo-Controlled Periods of UNCOVER-1, 2, and -3 Trials shows reported TEAEs of increased AST and ALT during the 12-week placebo-controlled periods of the pivotal UNCOVER-1, -2, and -3 trials in adult patients with psoriasis.6

Reports of Increased AST and ALT During 12-Week Placebo-Controlled Periods of UNCOVER-1, 2, and -3 Trials6

Preferred Term

IXE Q2W
(N=1167)
n (%)

IXE Q4W
(N=1161)
n (%)

PBO
(N=791)
n (%)

Increased AST

6 (0.5)

5 (0.4)

3 (0.4)

Increased ALT

5 (0.4)

4 (0.3)

2 (0.3)

Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; PBO = placebo.

Psoriatic Arthritis

Analyses of hepatic-related laboratory analytes and hepatic-related AEs do not demonstrate clinically important adverse effects related to ixekizumab treatment in patients with psoriatic arthritis. No patient in the psoriatic arthritis population met the laboratory screening criteria for potential drug-induced liver injury.6

Overall, the safety profile observed in patients with psoriatic arthritis treated with ixekizumab 80 mg every 4 weeks (Q4W) is consistent with the safety profile in patients with plaque psoriasis with the exception of the frequencies of influenza and conjunctivitis.6

Across 4 pooled psoriatic arthritis trials (N=1401, accounting for 2247.7 PYs of total ixekizumab exposure as of the March 19, 2021 database lock), 

  • increased ALT was reported in 37 patients (2.6%) with IR 1.6 per 100 PYs and
  • increased AST was reported in 28 patients (2.0%) with IR 1.2 per 100 PYs.6

Reports of Increased AST and ALT During 24-Week Placebo-Controlled Periods of SPIRIT-P1 and SPIRIT-P2 Trials shows reported TEAEs of increased AST and ALT during the 24-week placebo-controlled periods of the pivotal SPIRIT-P1 and SPIRIT-P2 trials in with psoriatic arthritis.6

Reports of Increased AST and ALT During 24-Week Placebo-Controlled Periods of SPIRIT-P1 and SPIRIT-P2 Trials6

Preferred Term

IXE Q4W
(N=229)

IXE Q2W
(N=225)

PBO
(N=224)

AST increased

3 (1.3)

4 (1.8)

2 (0.9)

ALT increased

3 (1.3)

5 (2.2)

1 (0.4)

Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; PBO = placebo.

Axial Spondyloarthritis

An integrated analysis of the phase 3 clinical trials demonstrated no clinically meaningful differences in the frequency of hepatic-related TEAEs across treatment groups. The most commonly reported hepatic-related TEAEs were ALT increased and AST increased. No patient met the laboratory screening criteria for potential drug-induced hepatotoxicity.6

Overall, the safety profile observed in patients with AS/r-axSpA treated with ixekizumab Q4W is consistent with the safety profile in patients with plaque PsO with the exception of IBD and rhinitis. The safety profile in patients with nr-axSpA is consistent with that of patients with plaque PsO with the exception of IBD, influenza, and conjunctivitis.6

Across 4 axial spondyloarthritis trials that included patients with AS/r-axSpA and nr-axSpA (N=932, accounting for 2096.2 PYs of total ixekizumab exposure as of the March 19, 2021 database lock),

  • increased ALT was reported in 38 patients (4.1%) with IR 1.8 per 100 PYs and
  • increased AST was reported in 34 patients (3.6%) with IR 1.6 per 100 PYs.6

Reports of Increased AST and ALT During 16-Week Placebo-Controlled Periods of COAST-V, COAST-W, and COAST-X Trials shows reported TEAEs of increased AST and ALT during the 16-week placebo-controlled periods of the pivotal COAST-V, COAST-W, and COAST-X trials in with AS/r-axSpA (COAST-V and COAST-W) and nr-axSpA (COAST-X).6

Reports of Increased AST and ALT During 16-Week Placebo-Controlled Periods of COAST-V, COAST-W, and COAST-X Trials6

Preferred Term

IXE Q4W
(N=291)

IXE Q2W
(N=283)

PBO
(N=294)

AST increased

3 (1.0)

2 (0.7)

3 (1.0)

ALT increased

4 (1.4)

1 (0.4)

3 (1.0)

Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; PBO = placebo.

References

1Taltz [summary of product characteristics]. Eli Lilly and Company (Ireland) Limited, Ireland

2Nash 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

3van 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

4Deodhar 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

5Griffiths CEM, Reich K, Lebwohl M, et al; UNCOVER-2, UNCOVER-3 Investigators. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386(9993):541-551. https://doi.org/10.1016/S0140-6736(15)60125-8

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

Date of Last Review: 23 May 2022


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