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).

What is the incidence of hypersensitivity events with Taltz® (ixekizumab)?

The overall incidence rate of hypersensitivity reactions with ixekizumab across 17 psoriasis trials was 5.6 per 100 patient-years.

UK_cFAQ_IXE359_HYPERSENSITIVITY_REACTION_PsO_PsA_axSpA
UK_cFAQ_IXE359_HYPERSENSITIVITY_REACTION_PsO_PsA_axSpA
en-GB

What is the Label Information Related to Hypersensitivity?

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

Hypersensitivity Reactions in the Clinical Trials

Note that multiple, different dosing regimens, including unapproved doses, are included in this response. Please refer to Taltz summary of product characteristics for full prescribing information. 

Psoriasis Clinical Trials

Integrated Data

Nonanaphylactic Hypersensitivity Events Reported at an Incidence Rate ≥0.1 Per 100 Patient-Years in Patients Exposed to Ixekizumab Across 17 Adult Psoriasis Clinical Trials characterizes nonanaphylactic hypersensitivity events across an integrated data set of 17 adult psoriasis clinical trials (N=6892 patients accounting for 18,025.7 patient-years [PY] of ixekizumab exposure through March 19, 2021).2

No cases of anaphylaxis were confirmed after medical reviews.2

The overall incidence rate of allergic/hypersensitivity reactions across the 17 adult psoriasis clinical trials was 5.6 per 100 PY.2

Nonanaphylactic Hypersensitivity Events Reported at an Incidence Rate ≥0.1 Per 100 Patient-Years in Patients Exposed to Ixekizumab Across 17 Adult Psoriasis Clinical Trials3

All Ixekizumab Exposures
(N=6892)
PY=18,025.7
n (IR)

Patients with ≥1 TEAE nonanaphylactic allergic reactions/hypersensitivity

991 (5.5)

Dermatitis contact

199 (1.1)

Eczema

194 (1.1)

Urticaria

157 (0.9)

Dermatitis

105 (0.6)

Rash

97 (0.5)

Rhinitis allergic

92 (0.5)

Dermatitis allergic

37 (0.2)

Hypersensitivity

36 (0.2)

Conjunctivitis allergic

29 (0.2)

Drug hypersensitivity

27 (0.1)

Dermatitis atopic

21 (0.1)

Hand dermatitis

17 (0.1)

Drug eruption

16 (0.1)

Angioedema

15 (0.1)

Rash pustular

10 (0.1)

Abbreviations: PY = patient-years; TEAE = treatment-emergent adverse event.

12-Week Induction Period

Most hypersensitivity or allergic reactions were mild in severity, and consisted mostly of various skin rashes.4

In the 12-week induction period of the 2 active comparator trials with etanercept (UNCOVER-2 and -3),

  • 2 patients receiving ixekizumab experienced a hypersensitivity event considered to be serious
    • One of the serious events (leukocytoclastic vasculitis) resulted in admission to the hospital. This patient, who was being treated with ixekizumab 80 mg every 2 weeks (Q2W) and had recently started taking lansoprazole, did not discontinue the study.4
    • The other serious event (facial angioedema), reported in a patient being treated with ixekizumab 80 mg every 4 weeks (Q4W), resulted in the patient discontinuing from the study.4
  • an additional ixekizumab-treated patient discontinued the study due to nonserious urticaria
  • across all treatments, <4% of patients reported experiencing an allergic or hypersensitivity reaction, and
  • allergic/hypersensitivity reaction rates were comparable for the ixekizumab 80 mg Q2W and Q4W dosing regimens.4

Hypersensitivity Reactions Through Week 12 in UNCOVER-1, -2, and -3 (Individual Studies, All Treatment Groups) provides the frequency of hypersensitivity reactions through week 12 of UNCOVER-1, -2, and -3.

Hypersensitivity Reactions Through Week 12 in UNCOVER-1, -2, and -3 (Individual Studies, All Treatment Groups)4,5

Hypersensitivity Reactionsa

IXE Q2W

IXE Q4W

ETN

PBO

UNCOVER-1

N

433

432

N/A

431

n (%)

12 (2.8)

17 (3.9)

N/A

8 (1.9)

UNCOVER-2

N

350

347

357

167

n (%)

13 (3.7)

14 (4.0)

11 (3.1)

3 (1.8)

UNCOVER-3

N

384

382

382

193

n (%)

12 (3.1)

11 (2.9)

7 (1.8)

4 (2.1)

Abbreviations: ETN = etanercept 50 mg twice weekly; IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; MedDRA = Medical Dictionary for Regulatory Activities; N/A = not applicable; PBO = placebo; SMQ = standard MedDRA query.

Note: No anaphylaxis events were reported during the 12-week induction period of UNCOVER-1, -2, and -3.

aTerm includes nonanaphylaxis reactions as defined by Hypersensitivity MedDRA SMQ narrow terms.

Psoriatic Arthritis Clinical Trials

Integrated Data

Nonanaphylactic Hypersensitivity Events Reported at an Incidence Rate ≥0.1 Per 100 Patient-Years in Patients Exposed to Ixekizumab Across 4 Psoriatic Arthritis Clinical Trials characterizes hypersensitivity events across a broader data set of 4 psoriatic arthritis clinical trials (N=1401 patients accounting for 2247.7 PY of ixekizumab exposure through March 19, 2021).6

No cases of anaphylaxis were confirmed after medical reviews.6

The overall incidence rate of allergic/hypersensitivity reactions across the 4 psoriatic arthritis clinical trials was 4.5 per 100 PY.6

Nonanaphylactic Hypersensitivity Events Reported at an Incidence Rate ≥0.1 Per 100 Patient-Years in Patients Exposed to Ixekizumab Across 4 Psoriatic Arthritis Clinical Trials3


All Ixekizumab Exposures
(N=1401)
PY=2247.7
n (IR)

Patients with ≥1 TEAE nonanaphylactic allergic reactions/hypersensitivity

101 (4.5)

Rash

19 (0.8)

Eczema

15 (0.7)

Drug hypersensitivity

10 (0.4)

Rhinitis allergic

10 (0.4)

Urticaria

6 (0.3)

Dermatitis atopic

5 (0.2)

Dermatitis contact

5 (0.2)

Hypersensitivity

5 (0.2)

Dermatitis

4 (0.2)

Dermatitis allergic

4 (0.2)

Drug eruption

4 (0.2)

Injection-related reaction

4 (0.2)

Angioedema

3 (0.1)

Conjunctivitis allergic

2 (0.1)

Erythema nodosum

2 (0.1)

Rash erythematous

2 (0.1)

Rash maculo-papular

2 (0.1)

Rash pruritic

2 (0.1)

Swelling of face

2 (0.1)

Swelling of eyelid

2 (0.1)

Abbreviations: PY = patient-years; TEAE = treatment-emergent adverse event.

24-Week Placebo-Controlled Treatment Period

In the 24-week double-blind treatment period of SPIRIT-P1, mild or moderate hypersensitivity events, most commonly manifesting as rash or urticaria, were reported in 7 patients in the total ixekizumab group (ixekizumab 80 mg Q4W and ixekizumab 80 mg Q2W groups combined).

  • None were reported as serious.
  • One patient treated with ixekizumab 80 mg Q4W discontinued the study due to rash.7

In the 24-week double-blind treatment period of SPIRIT-P2, significantly greater proportions of patients in the ixekizumab 80 mg Q4W group (8 [7%] patients; p=.0358) and ixekizumab Q2W group (9 [7%] patients; p=.0192) had allergic reactions or hypersensitivity events than did patients treated with placebo (1 [1%] patient).

  • All events were reported as either mild or moderate and the most common manifestations were angioedema, eczema, rash, or urticaria (2 patients for each manifestation).
  • No cases of anaphylaxis were reported.
  • One patient taking ixekizumab 80 mg Q4W discontinued treatment due to an allergic or hypersensitivity TEAE, a nonserious pruritic rash.8

Hypersensitivity Reactions Through Week 24 in SPIRIT-P1 and -P2 Trials (Individual Studies, All Treatment Groups) provides the incidence of hypersensitivity reactions through 24 weeks in SPIRIT-P1 and SPIRIT-P2.

Hypersensitivity Reactions Through Week 24 in SPIRIT-P1 and -P2 Trials (Individual Studies, All Treatment Groups)7,8

Hypersensitivity Reactions 

IXE Q4W

IXE Q2W

PBO

SPIRIT-P1

N

107

102

106

n (%)

2 (1.9)

5 (4.9)

3 (2.8)

SPIRIT-P2

N

122

123

118

n (%)

8 (7%)a

9 (7%)b

1 (1%)

Abbreviations: IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; PBO = placebo.

ap=.0358 vs PBO.

bp=.0192 vs PBO.

Axial Spondyloarthritis Clinical Trials

Integrated Data

Nonanaphylactic Hypersensitivity Events Reported at an Incidence Rate ≥0.1 Per 100 Patient-Years in Patients Exposed to Ixekizumab Across 4 Axial Spondyloarthritis Clinical Trials characterizes hypersensitivity events across a data set of 4 axial spondyloarthritis (axSpA) clinical trials (COAST-V and COAST-W AS/r-axSpA trials, COAST-X nr-axSpA trial, and COAST-Y long-term extension study in patients with axSpA) through March 19, 2021 from 932 patients (2096.2 PY).6

No cases of anaphylaxis were confirmed after medical reviews.6

The overall incidence rate of allergic/hypersensitivity reactions across the 4 axSpA clinical trials was 4.2 per 100 PY.6

Nonanaphylactic Hypersensitivity Events Reported at an Incidence Rate ≥0.1 Per 100 Patient-Years in Patients Exposed to Ixekizumab Across 4 Axial Spondyloarthritis Clinical Trials3


All Ixekizumab Exposures
(N=932)
PY=2096.2
n (IR)

Patients with ≥1 TEAE nonanaphylactic allergic reactions/hypersensitivity

88 (4.2)

Rash

24 (1.1)

Eczema

17 (0.8)

Dermatitis

11 (0.5)

Urticaria

10 (0.5)

Dermatitis allergic

5 (0.2)

Angioedema

3 (0.1)

Dermatitis atopic

3 (0.1)

Drug eruption

3 (0.1)

Erythema nodosum

3 (0.1)

Drug hypersensitivity

2 (0.1)

Erythema multiforme

2 (0.1)

Rash pruritic

2 (0.1)

Rash pustular

2 (0.1)

Abbreviations: PY = patient-years; TEAE = treatment-emergent adverse event.

16-Week Placebo-Controlled Treatment Periods of AS/r-axSpA Trials

During the 16-week double-blinded treatment period of the COAST-V trial, treatment-emergent allergic or hypersensitivity reactions were more frequent in the active treatment groups

During the 16-week double-blinded treatment period of the COAST-W trial, treatment-emergent allergic or hypersensitivity reactions were reported in

Hypersensitivity Reactions Through Week 16 in COAST-V and COAST-W Clinical Trials (Individual Studies, All Treatment Groups)9,10

Hypersensitivity Reactions 

IXE Q4W

IXE Q2W

ADA Q2W

PBO

COAST-V

N

81

83

90

86

n (%)

3 (4)

3 (4)

4 (4)

1 (1)

COAST-W

N

114

98

N/A

104

n (%)

3 (2.6)

6 (6.1)

N/A

1 (1.0)

Abbreviations: ADA = adalimumab; IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; N/A = not applicable; PBO = placebo.

52-Week Placebo-Controlled Treatment Period of nr-axSpA Trial

During the 52-week double-blinded treatment period of the COAST-X trial, treatment-emergent allergic or hypersensitivity reactions were reported in

  • 3 (3.0%) of 102 patients in the ixekizumab 80 mg Q2W group,
  • 4 (4.0%) of 96 patients in the ixekizumab 80 mg Q4W group, and
  • 4 (4.0%) of 104 patients in the placebo group.
  • No anaphylaxis events were reported during the 52-week double-blinded treatment period in patients treated with ixekizumab.11

Postmarketing Data

Rare events consistent with anaphylaxis (estimated as ≥0.01% to <0.1%) have been identified during postmarketing use of ixekizumab. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a relationship to ixekizumab exposure.3

Examples of serious allergic-type events with ixekizumab treatment in the postmarketing reports include

  • hives
  • lip swelling
  • difficulty breathing
  • difficulty swallowing
  • fast heartbeat
  • abdominal pain
  • itching
  • skin swelling
  • throat swelling
  • chest tightness
  • throat tightness
  • irregular heartbeat
  • redness of the skin, and
  • low blood pressure.3

References

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

2Griffiths CEM, Gooderham M, Colombel JF, et al. Safety of ixekizumab in adult patients with moderate-to-severe psoriasis: data from 17 clinical trials with over 18,000 patient-years of exposure. Poster presented at: Annual Meeting of the American Academy of Dermatology (AAD); March 25-29, 2022; Boston, MA.

3Data on file, Eli Lilly and Company and/or one of its subsidiaries.

4Griffiths 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

5Gordon K, Blauvelt A, Langley RG, et al. Ixekizumab for treatment of moderate-to-severe plaque psoriasis: 12-week results from a phase 3 study (UNCOVER-1). Poster presented at: 23rd World Congress of Dermatology; June 8-13, 2015; Vancouver, Canada.

6Schwartzman S, Deodhar A, Combe B, et al. Safety profile of ixekizumab for the treatment of psoriatic arthritis and axial spondyloarthritis up to 3 years: an updated integrated safety analysis. Poster presented at: Annual Meeting of the America College of Rheumatology (ACR Convergence Virtual); November 1-10, 2021.

7Mease 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

8Nash 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

9van 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

10Deodhar 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

11Deodhar 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

Date of Last Review: 10 March 2022


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