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): General Safety Information in Non-radiographic Axial Spondyloarthritis Clinical Trials

Safety information from the ixekizumab prescribing information and clinical trials are available in this response.

Ixekizumab Label Information Related to Safety

Contraindications

Ixekizumab is contraindicated in patients with serious hypersensitivity to the active substance or to any of the excipients.1

Ixekizumab is contraindicated in patients with clinically important active infections (e.g. active tuberculosis).1

Warnings and Precautions

Treatment with ixekizumab is associated with an increased rate of infections such as upper respiratory tract infection, oral candidiasis, conjunctivitis, and tinea infections. Ixekizumab should be used with caution in patients with clinically important chronic infection or a history of recurrent infection. Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur.1

If an infection develops,

  • patients should be carefully monitored and 

  • ixekizumab discontinued if

    • the patient is not responding to standard therapy or if

    • the infection becomes serious.1

Ixekizumab should not be resumed until the infection resolves.1

Ixekizumab must not be given to patients with active tuberculosis (TB).1

  • Anti-TB therapy prior to initiation of ixekizumab in patients with latent TB should be considered.1

Serious hypersensitivity reactions, including some cases of

  • anaphylaxis,

  • angioedema,

  • urticaria

  • and, rarely, late (10-14 days following injection) serious hypersensitivity reactions including

    • widespread urticaria,

    • dyspnea and

    • high antibody titres

have been reported.

If a serious hypersensitivity reaction occurs, administration of ixekizumab should be discontinued immediately and appropriate therapy initiated.1

Cases of new or exacerbations of inflammatory bowel disease have been reported with ixekizumab. Ixekizumab is not recommended in patients with inflammatory bowel disease. If a patient develops signs and symptoms of inflammatory bowel disease or experiences an exacerbation of pre-existing inflammatory bowel disease, ixekizumab should be discontinued and appropriate medical management should be initiated. 1

Ixekizumab should not be used with live vaccines. No data are available on the response to live vaccines; there are insufficient data on response to inactive vaccines.1

Adverse Drug Reactions

Adverse drug reactions are listed in Table 1.

Table 1. List of adverse reactions in clinical studies and postmarketing reports1

System organ class

Frequency

Adverse reaction

Infections and infestations

 

Very common

Upper respiratory tract infection

Common

Tinea infection, Herpes simplex (mucocutaneous)

Uncommon

Influenza, Rhinitis, Oral candidiasis, Conjunctivitis, Cellulitis 

Blood and lymphatic system disorders

Uncommon

Neutropenia, Thrombocytopenia

Immune system disorders

Uncommon

Angioedema

Rare

Anaphylaxis

Respiratory, thoracic and mediastinal disorders

Common

Oropharyngeal pain

Gastrointestinal disorders

Common

Nausea

Uncommon

Inflammatory bowel disease

Skin and subcutaneous disorders

Uncommon

Urticaria, Rash, Eczema,  

General disorders and administration site conditions

Very common

Injection site reactionsa

a See section description of selected adverse reactions

Adverse drug reactions in patients treated with ixekizumab (80 mg or 160 mg at week 0) by subcutaneous injection followed by 80 mg every 4 weeks in the nr-axSpA clinical trials were similar with the exception of the frequency of IBD (common, defined as occurring at a frequency of ≥1% and <10%), influenza (common), and conjunctivitis (common).2

Treatment-Emergent Adverse Events Reported in nr-axSpA Trials

Treatment-emergent adverse events were evaluated using MedDRA terms.

Treatment-emergent adverse events were defined as events that first occurred or worsened in severity, relative to baseline, at any time during a clinical study. Treatment-emergent adverse events reported during the studies are not always attributed to study medications and the frequencies do not reflect investigator assessment of causality.2

Serious Adverse Event Definition

In ixekizumab clinical trials, an SAE was defined as any AE that resulted in

  • death

  • initial or prolonged inpatient hospitalization

  • a life-threatening experience (that is, immediate risk of dying)

  • persistent or significant disability/incapacity,

  • congenital anomaly/birth defect, and

  • considered significant by the investigator for any other reason.3

Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious adverse drug events when, based upon appropriate medical judgement, they may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.3

Treatment-Emergent Adverse Events Reported in Double-Blind Treatment Period of COAST-X

Most TEAEs for both ixekizumab 80 mg Q2W and ixekizumab 80 mg Q4W dosing regimens were mild-to-moderate in severity. The frequency of TEAEs were similar for both ixekizumab dosing regimens.

The most frequent TEAEs (defined as occurring in ≥5% of patients receiving ixekizumab) were nasopharyngitis, injection site reaction, headache, upper respiratory tract infection, and hypertension. Adverse events during the double-blind treatment period are summarized in Table 2.4

 

Table 2. Adverse Events During the 52-Week Double-Blind Treatment Period of COAST-X2,4

 

PBO
N=104
n (%)

IXE Q2W
N=102
n (%)

IXE Q4W
N=96
n (%)

TEAEsa

60 (57)

79 (77)

63 (66)

Severeb

4 (4)

7 (7)

1 (1)

Discontinuation due to AE

2 (2)

1 (1)

1 (1)

Serious AE

1 (1)c

1 (1)d

2 (2)e

Death

0

0

0

Common Adverse Eventsf

Nasopharyngitis

8 (8)

16 (16)

18 (19)

Injection site reaction

4 (4)

17 (17)

11 (11)

Headache

4 (4)

5 (5)

7 (7)

Upper respiratory tract infection

4 (4)

6 (6)

4 (4)

Hypertension

3 (3)

4 (4)

6 (6)

Adverse events of special interest

Neutropeniag

Grade 1

8 (8)

13 (13)

11 (11)

Grade 2

0

2 (2)

1 (1)

Grade 3

0

0

0

Grade 4

1 (1)

0

0

Hepatic eventsh

6 (6)

5 (5)

3 (3)

Infections

30 (29)

43 (42)

38 (40)

Serious infections

0

0

1 (1)i

Oral candidiasis

1 (1)

0

0

Herpes zoster

1 (1)

0

2 (2)

Reactivated TB

0

0

0

Injection site reactions 

7 (7)

25 (25)

18 (19)

Severe

0

2 (2)

0

Allergic reactions and hypersensitivities

4 (4)

3 (3)

4 (4)

Potential anaphylaxis

1 (1)

0

0

Cerebrocardiovascular eventsj

0

1 (1)

0

Malignancies

0

0

0

IBDj

1 (1)

0

1 (1)

Depression

0

4 (4)k

0

Abbreviations: AE = adverse event; IBD = inflammatory bowel disease; IXE Q2W = ixekizumab 80 mg every 2 weeks after a 160 mg or 80 mg starting dose; IXE Q4W = ixekizumab 80 mg every 4 weeks after a 160 mg starting dose; PBO = placebo; TB = tuberculosis; TEAEs = treatment-emergent adverse events.

a TEAEs were summarized using the safety population, defined as all patients who received at least 1 dose of the trial drug, per the assigned treatment. TEAEs were summarized before any switch to open-label ixekizumab.

b Patients with multiple occurrences of the same event are counted under the event with the highest severity.

c Anaphylactoid reaction.

d Major depression.

e Abdominal pain, erysipelas.

f Common TEAEs were defined as those that occurred at a frequency of at least 5% for patients receiving ixekizumab (both dosing regimens combined).

g Neutropenia percentages are calculated for patients with a baseline and at least one postbaseline value: placebo, n =102; ixekizumab Q4W, n = 96; ixekizumab Q2W, n = 102.

h Patients with ≥1 hepatic-related TEAE; most were due to transaminase elevations.

i Erysipelas

j Adjudicated by an external committee.

k One patient with preexisting anxiety was withdrawn from the study by the physician due to a TEAE of suicidal ideation after switching to open-label ixekizumab.

Note: The dosing schedule IXE Q2W is not consistent with the approved dosing schedule for axial spondyloarthritis. Please refer to the Taltz Summary of Product Characteristics for approved dosing.1

References

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

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

3. Gordon 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

4. Deodhar 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

Glossary

AE = adverse event

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

IBD = inflammatory bowel disease

MedDRA = Medical Dictionary for Regulatory Activities

nr-axSpA = nonradiographic axial spondyloarthritis

PY = patient-years

Q2W = every 2 weeks

Q4W = every 4 weeks

SAE = serious adverse event

TB = tuberculosis

TEAE = treatment-emergent adverse event

TNF = tumor necrosis factor

Date of Last Review: February 28, 2020


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