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Taltz ® (ixekizumab) injection
80 mg/mL
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What is the incidence of hypersensitivity events with Taltz® (ixekizumab)?
The overall incidence rate of hypersensitivity reactions across 17 psoriasis trials using the original commercial ixekizumab formulation was 5.6 per 100 patient-years. Hypersensitivity events reported with citrate-free ixekizumab are also included.
Prescribing Information Related to Hypersensitivity Reactions
Contraindication: Ixekizumab is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients.1
Warnings and Precautions: Serious hypersensitivity reactions, including angioedema and urticaria (each ≤0.1%), occurred in the ixekizumab group in clinical trials. Anaphylaxis, including cases leading to hospitalization, has been reported in postmarketing use with ixekizumab. If a serious hypersensitivity reaction occurs, discontinue ixekizumab immediately and initiate appropriate therapy.1
Original Commercial Ixekizumab Formulation and Citrate-Free Ixekizumab Formulation
The original commercial formulation of ixekizumab was used in clinical trials conducted in patients with moderate-to-severe plaque psoriasis, active psoriatic arthritis, ankylosing spondylitis/radiographic axial spondyloarthritis (AS/r-axSpA), and nonradiographic axial spondyloarthritis (nr-axSpA). Information is available in Hypersensitivity Reactions in Trials Using Original Commercial Ixekizumab Formulation.
Citrate-free ixekizumab was studied in clinical trials conducted in healthy participants.2,3 Information is available in Hypersensitivity Reactions in Trials Using Citrate-Free Ixekizumab.
Hypersensitivity Reactions in Trials Using Citrate-Free Ixekizumab
Trials of citrate-free ixekizumab conducted in healthy participants were not designed to compare the incidence of hypersensitivity reactions with citrate-free ixekizumab and the original commercial ixekizumab formulation. Hypersensitivity reactions were reported as treatment-emergent adverse events (unsolicited data).4
RHCS was a phase 1 clinical trial in healthy volunteers that compared the tolerability of the original commercial ixekizumab formulation to 2 alternate citrate-free test formulations. No participants experienced hypersensitivity adverse events during the RHCS trial.2,4
RHCU was a phase 1 clinical trial in healthy volunteers that evaluated bioequivalence of citrate-free ixekizumab to the original commercial ixekizumab formulation. No participants experienced systemic hypersensitivity adverse events during the RHCU trial.3,4
Treatment-emergent adverse events were evaluated using Medical Dictionary for Regulatory Activities (MedDRA) terms. Treatment-emergent adverse events (TEAEs) were defined as events that first occurred or worsened in severity, relative to baseline, at any time during a clinical study. The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a TEAE of the type listed. Adverse events reported during the studies were not necessarily caused by the therapy and the frequencies do not reflect investigator assessment of causality.4
Hypersensitivity Reactions in Trials Using Original Commercial Ixekizumab Formulation
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 2022).5
No cases of anaphylaxis were confirmed after medical reviews.6,7
The overall incidence rate of allergic/hypersensitivity reactions across the 17 adult psoriasis clinical trials was 5.6 per 100 PY.5
All Ixekizumab Exposures |
|
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.8
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 and had recently started taking lansoprazole, did not discontinue the study.8
- The other serious event (facial angioedema), reported in a patient being treated with ixekizumab 80 mg every 4 weeks, resulted in the patient discontinuing from the study.8
- 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 every 2 weeks and every 4 weeks dosing regimens.8
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 Reactionsa |
IXE 80 mg |
IXE 80 mg |
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 = ixekizumab; 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 2022).4,5
No cases of anaphylaxis were confirmed after medical reviews.5,10
The overall incidence rate of allergic/hypersensitivity reactions across the 4 psoriatic arthritis clinical trials was 4.5 per 100 PY.5
All Ixekizumab Exposures |
|
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 every 4 weeks and ixekizumab 80 mg every 2 weeks groups combined).
- None were reported as serious.
- One patient treated with ixekizumab 80 mg every 4 weeks discontinued the study due to rash.11
In the 24-week double-blind treatment period of SPIRIT-P2, significantly greater proportions of patients in the ixekizumab 80 mg every 4 weeks group (8 [7%] patients; p=.0358) and ixekizumab every 2 weeks 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 every 4 weeks discontinued treatment due to an allergic or hypersensitivity TEAE, a nonserious pruritic rash.12
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 |
IXE 80 mg |
IXE 80 mg |
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 = ixekizumab; 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 2022 from 932 patients (2097.7 PY).5
The overall incidence rate of allergic/hypersensitivity reactions across the 4 axSpA clinical trials was 4.2 per 100 PY.5
All Ixekizumab Exposures |
|
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 |
2 (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 (3 [4%] of 83 patients in the ixekizumab 80 mg every 2 weeks group, 3 [4%] of 81 patients in the ixekizumab 80 mg every 4 weeks group, 4 [4%] of 90 patients in the adalimumab group) than in the placebo group (1 [1%] of 86 patients) (Hypersensitivity Reactions Through Week 16 in COAST-V and COAST-W Clinical Trials (Individual Studies, All Treatment Groups)). All of these events were nonanaphylactic events.13
During the 16-week double-blinded treatment period of the COAST-W trial, treatment-emergent allergic or hypersensitivity reactions were reported in 6 (6.1%) of 98 patients in the ixekizumab 80 mg every 2 weeks group, 3 (2.6%) of 114 patients in the ixekizumab 80 mg every 4 weeks group, and 1 (1.0%) of 104 patients in the placebo group (Hypersensitivity Reactions Through Week 16 in COAST-V and COAST-W Clinical Trials (Individual Studies, All Treatment Groups)). No anaphylaxis events were reported during the 16-week double-blinded treatment period.14
Hypersensitivity Reactions |
IXE 80 mg |
IXE 80 mg |
ADA |
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 = ixekizumab; 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 every 2 weeks group, 4 (4.0%) of 96 patients in the ixekizumab 80 mg every 4 weeks 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.15
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.4
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.4
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2024.
2Study of ixekizumab in healthy participants. ClinicalTrials.gov identifier: NCT03848403. Updated November 30, 2022. Accessed December 9, 2022. https://clinicaltrials.gov/show/NCT03848403
3A study of two formulations of ixekizumab in healthy participants. ClinicalTrials.gov identifier: NCT04259346. Updated April 8, 2022. Accessed December 9, 2022. https://clinicaltrials.gov/show/NCT04259346
4Data on file, Eli Lilly and Company and/or one of its subsidiaries.
5Deodhar A, Blauvelt A, Lebwohl M, et al. Long-term safety of Ixekizumab in adults with psoriasis, psoriatic arthritis, or axial spondyloarthritis: a post-hoc analysis of final safety data from 25 randomized clinical trials. Arthritis Res Ther. 2024;26(1):49. https://doi.org/10.1186/s13075-023-03257-7
6Griffiths 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.
7Griffiths 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. Dermatol Ther (Heidelb). 2022;12(6):1431-1446. https://doi.org/10.1007/s13555-022-00743-9
8Griffiths 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
9Gordon 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.
10Deodhar AA, Combe B, Accioly AP, et al. Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure. Ann Rheum Dis. 2022;81(7):944-950. https://doi.org/10.1136/annrheumdis-2021-222027
11Mease 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
12Nash 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
13van 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
14Deodhar 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
15Deodhar 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: November 21, 2022