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)

Safety of Taltz® (ixekizumab) in Patients from Psoriatic Arthritis Clinical Trials

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

UK_cFAQ_IXE027_GENERAL_SAFETY_PsA
UK_cFAQ_IXE027_GENERAL_SAFETY_PsA
en-GB

What are the General Safety Information from the Label?

Hypersensitivity: Ixekizumab is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients (Sodium citrate, Citric acid Anhydrous, Sodium chloride, Polysorbate 80, Water for injections).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

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

Treatment with ixekizumab is associated with an increased rate of infections such as upper respiratory tract infection, oral candidiasis, conjunctivitis, and tinea infections.1

Ixekizumab should be used with caution in patients with clinically important chronic infection or a history of recurrent infection. 1

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

Inflammatory Bowel Disease (including Crohn's disease and ulcerative colitis): 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

Immunisations: 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

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 reactions

Treatment-Emergent Adverse Events Reported in the Double-Blind Treatment Period of SPIRIT-P1 and -P2

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

SPIRIT-P1

SPIRIT-P1 Safety Overview During Double-Blind Treatment Period (Ixekizumab and Placebo Groups)2,3

 

PBO
N=106
n (%)

IXE Q4W
N=107
n (%)

IXE Q2W
N=102
n (%)

TEAE

50 (47.2)

71 (66.4) 

67 (65.7) 

Mild

27 (25.5)

43 (40.2) 

41 (40.2) 

Moderate

21 (19.8)

24 (22.4)

21 (20.6)

Severe

2 (1.9)

4 (3.7)

5 (4.9)

SAEs

2 (1.9)a

6 (5.6)b

3 (2.9)c

DC due to AE

2 (1.9)

2 (1.9)

4 (3.9)

AEs of Special Interestd

36 (34.0)

52 (48.6) 

56 (54.9) 

Infection

27 (25.5)

30 (28.0)

24 (23.5)

Any candida Infection

0

1 (0.9)

1 (1.0)

Active or reactivated tuberculosis

0

0

0

Injection site reactions

5 (4.7)

26 (24.3) 

27 (26.5) 

Hepatic event

7 (6.6)

5 (4.7)

9 (8.8)

Allergic reaction/hypersensitivity

3 (2.8)

2 (1.9)

5 (4.9)

Cytopenia (all types)

6 (5.7)

1 (0.9)

4 (3.9)

Neutropenia

0

0

1 (1.0)

Depression

0

2 (1.9)

1 (1.0)

Cerebrocardiovascular event

0

0

0

Malignancy

1 (0.9)

0

0

Abbreviations: AE = adverse event; DC = discontinuation; IXE Q2W = 80 mg ixekizumab every 2 weeks following a 160 mg starting dose; IXE Q4W = 80 mg ixekizumab every 4 weeks following a 160 mg starting dose; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo every 2 weeks; SAE = serious adverse event; TEAE = treatment-emergent adverse event.

aThe 2 SAEs were Bartholin's cyst and hepatic enzyme increased.

bSix patients reported a total of 8 SAEs (more than 1 event occurred in a single patient): gastroenteritis, pancreatitis acute, post-traumatic headache, uterine polyp, cholelithiasis, fall, fibula fracture, and lumbar spinal stenosis.

cThree patients reported a total of 5 SAEs (more than 1 event occurred in a single patient): herpes zoster, esophageal candidiasis, impaired gastric emptying, cervical myelopathy, and acquired phimosis.

dReported as adverse events and coded using MedDRA v17.1. Groups of adverse events of special interest are shown.

SPIRIT-P2

SPIRIT-P2 Safety Overview During 24 Week Double-Blind Treatment Period4

 

PBO
N=118
n (%)

IXE Q4W
N=107
n (%)

IXE Q2W
N=102
n (%)

TEAE

76 (64)

83 (68) 

90 (73)

Mild

32 (27)

48 (39)

43 (35)

Moderate

42 (36)

31 (25)

38 (31)

Severe

2 (2)

4 (3)

9 (7)

SAE

4 (3)a

3 (2)b

8 (7)c

AEs of Special Interest 

Infection

35 (30.0)

47 (39)

47 (38)

Any candida infection

0

2 (2)

6 (5)

Active or reactivated tuberculosis

0

0

0

Injection site reactions

5 (4)

14 (11)b

29 (24)

Hepatic event

2 (2)

2 (2)

5 (4)

Allergic reaction/hypersensitivity

1 (1)

8 (7)

9 (7)

Cytopenia (all types)

6 (5.7)

1 (0.9)

4 (3.9)

Neutropenia

0

0

1 (1.0)

Depression

3 (3)

2 (2)

2 (2)

Cerebrocardiovascular event

2 (2)

0

0

Malignancy

1 (0.9)

0

0

DC due to AE

6 (5)

5 (4)

8 (7)

Abbreviations: AE = adverse event; DC = discontinuation; IXE Q2W = 80 mg ixekizumab every 2 weeks; IXE Q4W = 80 mg ixekizumab every 4 weeks; PBO = placebo every 2 weeks; SAE = serious adverse event; TEAE = treatment-emergent adverse event.

aFour patients reported a total of 5 SAEs (more than 1 event occurred in a single patient): abdominal pain, femoral neck fracture, tendon rupture, adnexa uteri cyst, and peripheral arterial occlusive disease.

bThree patients reported a total of 4 SAEs (more than 1 event occurred in a single patient): vertigo, myofascial pain syndrome, prostate cancer, and cervicobrachial syndrome.

cEight patients reported a total of 10 SAEs (more than 1 event occurred in a single patient): abscess jaw, anal abscess, perirectal abscess, iron deficiency anemia, vertigo, anal fistula, foot fracture, diabetes mellitus, spontaneous abortion, and uterine prolapse.

Integrated Safety Data Across 4 Psoriatic Arthritis Clinical Trials

The integrated safety dataset includes data through March 19, 2020 from 4 clinical trials in patients with active PsA, including pivotal phase 3 trials SPIRIT-P1 and -P2, phase 3 trial SPIRIT-P3, and phase 4 trial SPIRIT-H2H (N=1401, accounting for 2247.7 PYs of total ixekizumab exposure).5

Treatment-Emergent Adverse Events and Serious Adverse Events in All Treatment Periods in All Psoriatic Arthritis Ixekizumab Exposures Integrated Analysis Set Through March 20205

Event, n (%) [IR]a

Pooled IXE
(N=1401; PY=2247.7)

Patients with ≥1 TEAEb

1131 (80.7) [50.3]c

Mild

461 (32.9) [20.5]

Moderate

556 (39.7) [24.7]

Severe

114 (8.1) [5.1]

Patients with ≥1 SAE

134 (9.6) [6.0]

Deaths

6 (0.4) [0.3]

Discontinuation due to AE

115 (8.2) [5.1]

Abbreviations: AE = adverse event; IR = incidence rate; IXE = ixekizumab; PY = patient-years; SAE = serious adverse event; TEAE = treatment-emergent adverse event.
Note: Patients with multiple occurrences of the same event are categorized by the highest severity. Deaths are included among SAEs and among discontinuations due to AEs.

aIncidence rate per 100 PYs.

bPatients with multiple occurrences of the same event were counted under the highest severity.

cThe most commonly reported TEAEs (IR per 100 PYs) were nasopharyngitis (9.0), upper respiratory tract infection (8.3), and injection site reactions (6.9).

Adverse Events of Special Interest in All Treatment Periods in All Psoriatic Arthritis Ixekizumab Exposures Integrated Analysis Set Through March 20205

Event, n (%) [IR]

Pooled IXE
(N=1401; PY=2247.7)

Infections

759 (54.2) [33.8]

Serious infections

28 (2.0) [1.2]

Candida infections

45 (3.2) [2.0]

Potential opportunistic infections

40 (2.9) [1.8]

Injection site reactionsa

260 (18.6) [11.6]

Hepatic reactionsb

112 (8.0) [5.0]

Allergic/hypersensitivity reactions 

102 (7.3) [4.5]

Cytopeniasc

56 (4.0) [2.5]

Inflammatory bowel disease (adjudicated)d

3 (0.2) [0.1]e

MACE (adjudicated)

12 (0.9) [0.5]

Malignancies

15 (1.1) [0.7]

Depression

37 (2.6) [1.6]

Abbreviations: IBD = inflammatory bowel disease; IR = incidence rate; IXE = ixekizumab; MACE = major adverse cerebrocardiovascular events; MedDRA = Medical Dictionary for Regulatory Activities; PY = patient-years; SMQ = Standardized MedDRA Query.

aBroad according to SMQ classification.

bThe most common hepatic reactions were alanine aminotransferase increased (n=37), aspartate aminotransferase increased (n=28), gamma-glutamyltransferase increased (n=21), and hepatic steatosis (n=21).

cBroad according to SMQ classification. The most common cytopenias were neutropenia (n=29), leukopenia (n=18), and neutrophil count decreased (n=9).

dThe data represent cases classified as “definite” and “probable” per external adjudication.

eThree patients had events of IBD confirmed by adjudication. One patient had more than 1 event. Crohn's disease (n=2); ulcerative colitis (n=1).

References

1Taltz [Summary of Product Characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2Mease 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

3Mease PJ, van der Heijde D, Ritchlin CT, et al. A randomized, double-blind, active- and placebo-controlled phase 3 study of efficacy and safety of ixekizumab, adalimumab, and placebo therapy in patients naïve to biologic disease modifying anti-rheumatic drugs with active psoriatic arthritis. Arthritis Rheumatol. 2015;67(suppl 10):997. 2015 ACR/ARHP Annual Meeting abstract 997. https://acrabstracts.org/abstract/a-randomized-double-blind-active-and-placebo-controlled-phase-3-study-of-efficacy-and-safety-of-ixekizumab-adalimumab-and-placebo-therapy-in-patients-naive-to-biologic-disease-modifying-anti/.

4Nash 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

5Sesin 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.

Glossary

AE = adverse event

CD = Crohn's disease

IBD = inflammatory bowel disease

PsA = psoriatic arthritis

PY = patient-years

SAE = serious adverse event

TB = tuberculosis

TEAE = treatment-emergent adverse event

UC = ulcerative colitis

Date of Last Review: April 27, 2021


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