Taltz ® (ixekizumab)

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Are injection site reactions with Taltz® (ixekizumab) frequent?

ISRs were more frequently reported with ixekizumab compared with placebo in trials in patients with PsO, PsA, or axSpA.

UK_cFAQ_IXE040_X1_INJECTION_SITE_REACTIONS_PsO_PsA_axSpA
UK_cFAQ_IXE040_X1_INJECTION_SITE_REACTIONS_PsO_PsA_axSpA
en-GB

Injection Site Reactions in Clinical Trials

Injection site reactions (ISR) were reported in 15.1% (1004/6645) of patients across 16 adult and pediatric psoriasis trials.1

The majority of reported ISRs in pivotal phase 3 psoriasis trials

  • occurred after the initial 160-mg starting dose
  • were mild-to-moderate in severity
  • decreased over time, and
  • did not lead to discontinuation.2-4

A similar safety profile was observed with ISRs in psoriasis (PsO) and psoriatic arthritis (PsA) clinical trials.3

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.

Injection Site Reactions in Patients with Psoriasis

Psoriasis Integrated Data

Injection site reactions were reported as an adverse event in 15.3% (1056/6892) (incidence rate [IR]=5.9 per 100 patient-years [PYs] of exposure) of patients exposed to ixekizumab across 17 adult psoriasis trials as of March 19, 2021.5 Of these, Incidence of Injection Site Reactions in All Patients Exposed to Ixekizumab Across 17 Adult Psoriasis Clinical Trials summarizes the most commonly reported types of ISRs.

Incidence of Injection Site Reactions in All Patients Exposed to Ixekizumab Across 17 Adult Psoriasis Clinical Trials3,5

 

All Ixekizumab Exposures Across 17 Adult Psoriasis Trials
N=6892; 18,025.7 PYs of Exposure
n (%) [IR]

Injection site reactions

1056 (15.3) [5.9]

Injection site reaction (unspecified)

698 (10.1) [3.9]

Injection site erythema

203 (2.9) [1.1]

Injection site pain

117 (1.7) [0.6]

Abbreviations: IR = incidence rate per 100 patient-years of exposure; PY = patient-year.

The incidence of ISRs decreased over time in psoriasis trials with an IR of 16.0 per 100 patient-years (PYs) during year 0 to 1 to 

  • 4.0 per 100 PYs during years 1 to 2, and 
  • 2.0 per 100 PYs during years 2 to 5.1

In the adult plaque psoriasis studies, injection site reactions were more common in subjects with a body weight <60 kg compared with the group with a body weight ≥60kg (25% vs. 14% for the combined Q2W and Q4W groups).4

Data From 12-Week, Double-Blind, Placebo-Controlled Induction Period

Most ISRs (≥95%) were mild-to-moderate in severity. Of patients who reported an ISR, 0.2% discontinued ixekizumab due to ISR.6,7

Frequency of Injection Site Reactions During 12-Week Induction Periods of UNCOVER-1, -2, and -3 Psoriasis Trials summarizes the most commonly reported types of ISRs during the 12-week induction periods of UNCOVER-1, -2, and -3 for the ixekizumab 80 mg every 2 weeks (Q2W) and every 4 weeks (Q4W) dosing groups and placebo.

Frequency of Injection Site Reactions During 12-Week Induction Periods of UNCOVER-1, -2, and -3 Psoriasis Trials2,3


IXE Q2W
(N=1167) 
n (%)

IXE Q4W
(N=1161)
n (%)

PBO
(N=791)
n (%)

Injection site reaction (unspecified)

117 (10.0)a

89 (7.7)a

9 (1.1)

Injection site erythema

52 (4.5)a

32 (2.8)a

2 (0.3)

Injection site pain

28 (2.4)

17 (1.5)

14 (1.8)

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

ap<.001 vs PBO.

Additional Patient Follow-Up on Injection Site Reactions

Patients who reported an ISR of any type during psoriasis trials were given a follow-up form to collect additional information. Follow-up forms of patients who spontaneously reported an ISR of any type showed that 51% reported pain, the majority (>90%) of which were categorized by the patient as mild-to-moderate in severity.3

  • The majority of reported ISRs in UNCOVER-1, -2, and -3 occurred following the initial 160-mg starting dose.3 Median time to onset was 7 days for the first 160-mg dose. For those with multiple ISRs reported, subsequent doses had earlier median time to onset of 1.5 days for weeks 2 and 4 injections.2
  • The median duration of ISRs was 2 days.8
  • Generally, injection site pain was typically reported to occur during injection and erythema onset was delayed.2
  • Timing of ISRs varied depending on treatment group (ixekizumab 80 mg Q2W and Q4W dosing groups, etanercept, or placebo) and symptom reported.9

Injection Site Reactions in Patients with Psoriatic Arthritis

Psoriatic Arthritis Integrated Data

Injection site reactions were reported as an adverse event in 18.6% (260/1401) (IR=11.6 per 100 PYs of exposure) of patients exposed to ixekizumab across 4 psoriatic arthritis trials (SPIRIT-P1, SPIRIT-P2, SPIRIT-P3, and SPIRIT-H2H) as of March 19, 2021.10 Of these, Incidence of Injection Site Reactions in All Patients Exposed to Ixekizumab Across 4 Psoriatic Arthritis Trials summarizes the most commonly reported types of ISRs.

Incidence of Injection Site Reactions in All Patients Exposed to Ixekizumab Across 4 Psoriatic Arthritis Trials3,10

 

All Ixekizumab Exposures Across 4 Psoriatic Arthritis Trials
(N=1401; 2247.7 PYs of Exposure)
n (%) [IR]

Injection site reactions

260 (18.6) [11.6]

Injection site reaction (unspecified)

156 (11.1) [6.9]

Injection site erythema

60 (4.3) [2.7]

Injection site pain 

22 (1.6) [1.0]

Abbreviations: IR = incidence rate per 100 patient-years of exposure; PY = patient-year.

The incidence of ISRs decreased over time in psoriatic arthritis trials with an IR of 22.0 per 100 PYs during year 0 to 1 to 

  • 4.0 per 100 PYs during year 1 to 2, and 
  • 2.0 per 100 PYs during year 2 to 3.11

In the psoriatic arthritis studies, injection site reactions were more common in subjects with a body weight <100 kg compared with the group with a body weight ≥100 kg (24% vs. 13% for the combined Q2W and Q4W groups).4

Data From 24-Week Double-Blind Treatment Periods of SPIRIT-P1 and SPIRIT-P2 Trials

Most ISRs (>95%) were mild-to-moderate in severity.3,12 Of patients who reported an ISR, 1.1% discontinued ixekizumab due to ISR.12,13

Frequency of Injection Site Reactions During 24-week Placebo-Controlled Periods of SPIRIT-P1 and SPIRIT-P2 Psoriatic Arthritis Trials summarizes the most commonly reported types of ISRs during the 24-week placebo-controlled periods of SPIRIT-P1 and SPIRIT-P2 for the ixekizumab 80 mg Q2W and Q4W dosing groups and placebo.

Frequency of Injection Site Reactions During 24-week Placebo-Controlled Periods of SPIRIT-P1 and SPIRIT-P2 Psoriatic Arthritis Trials3


IXE Q2W
(N=225)
n (%)

IXE Q4W
(N=229)
n (%)

PBO
(N=224)
n (%)

Injection site reaction (unspecified)

32 (14.2)a

22 (9.6)a

1 (0.4)

Injection site erythema

17 (7.6)a

9 (3.9)b

0

Injection site hypersensitivity 

6 (2.7)c

1 (0.4)

0

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

ap<.001 vs PBO.

bp<.005 vs PBO.

cp<.05 vs PBO.

In addition to the most commonly reported types of ISRs, as listed in Frequency of Injection Site Reactions During 24-week Placebo-Controlled Periods of SPIRIT-P1 and SPIRIT-P2 Psoriatic Arthritis Trials, injection site pain was reported in 

  • 0.9% of patients in both the ixekizumab 80 mg Q2W and Q4W groups, and
  • 2.2% of patients in the placebo group.3

The first occurrence of ISRs was most often within the first 6 weeks of treatment in the SPIRIT-P1 and SPIRIT-P2 studies. The median duration of ISRs was 3 days.3

Additional Patient Follow-Up on Injection Site Reactions

Patients who reported an ISR of any type during trials were given a follow-up form to collect additional information. Follow-up of patients who spontaneously reported an ISR of any type treated with ixekizumab 80 mg Q4W showed that 32.5% reported pain, the majority (>90%) of which were categorized by the patient as mild-to-moderate in severity.3

Injection Site Reactions in Patients with Axial Spondyloarthritis

Axial Spondyloarthritis Integrated Data

Injection site reactions were reported as an adverse event in 16.7% (156/932) [IR= 7.4 per 100 PYs of exposure] of patients across 4 axial spondyloarthritis (axSpA) trials (including AS/r-axSpA and nr-axSpA trials) as of March 19, 2021.10 Of these, Incidence of Injection Site Reactions in All Patients Exposed to Ixekizumab Across 4 Axial Spondyloarthritis Trials summarizes the most commonly reported types of ISRs.

Incidence of Injection Site Reactions in All Patients Exposed to Ixekizumab Across 4 Axial Spondyloarthritis Trials3,10

 

All Ixekizumab Exposures Across 4 axSpA Trials
(N=932; 2096.2 PYs of Exposure)
n (%) [IR]

Injection site reactions 

156 (16.7) [7.4]

Injection site reaction (unspecified)

93 (10.0) [4.4]

Injection site erythema

33 (3.5) [1.6]

Injection site swelling

16 (1.7) [0.8]

Abbreviations: axSpA = axial spondyloarthritis; IR = incidence rate per 100 patient-years; PY = patient-year.

The incidence of ISRs decreased over time in axSpA trials with an IR of 18.2 per 100 PYs during year 0 to 1 to 2.6 per 100 PYs during year 1 to 2.14

In the axial spondyloarthritis studies, injection site reactions were similar in subjects with a body weight <100 kg compared with the group with a body weight ≥100 kg (14% vs. 9% for the combined Q2W and Q4W groups).4

Data From 16-Week Double-Blind, Placebo-Controlled Treatment Periods of COAST-V and COAST-W AS/r-axSpA Trials

Most ISRs (>95%) were mild-to-moderate in severity.3,15,16 Of patients who reported an ISR, 1.1% discontinued ixekizumab due to ISR.15,16

Frequency of Injection Site Reactions During 16-Week Placebo-Controlled Periods of COAST-V and COAST-W AS/r-axSpA Trials summarizes the most commonly reported types of ISRs during the 16-week placebo-controlled periods of COAST-V and COAST-W for the ixekizumab 80 mg Q2W and Q4W dosing groups and placebo.

Frequency of Injection Site Reactions During 16-Week Placebo-Controlled Periods of COAST-V and COAST-W AS/r-axSpA Trials3

 

IXE Q2W
(N=181)
n (%)

IXE Q4W 
(N=195)
n (%)

PBO
(N=190)
n (%)

Injection site reaction (unspecified)

15 (8.3)

3 (1.5)

3 (1.6)

Injection site pain

5 (2.8)

4 (2.1)

4 (2.1)

Injection site erythema

4 (2.2)

3 (1.5)

1 (0.5)

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

  • The frequency and exposure-adjusted IR was greater during the first 2 weeks of treatment compared with later 2-week intervals.3
  • The median duration of ISRs was 2.8 days.3

Data From 52-Week Double-Blind, Placebo-Controlled Treatment Period of COAST-X nr-axSpA Trial

Injection site reactions were reported in 21.7% (43/198) of patients with nr-axSpA treated with ixekizumab during the 52-week double-blind treatment period of COAST-X.17

Most ISRs (>95%) were mild-to-moderate in severity. Of patients who reported ISR, 1.6% discontinued due to ISR.17

Incidence of Injection Site Reactions During 52-Week Placebo-Controlled Period of COAST-X Clinical nr-axSpA Trial summarizes the most commonly reported types of ISRs during the 52-week placebo-controlled period of COAST-X for the ixekizumab 80 mg Q2W and Q4W dosing groups and placebo are shown in Incidence of Injection Site Reactions During 52-Week Placebo-Controlled Period of COAST-X Clinical nr-axSpA Trial.

Incidence of Injection Site Reactionsa During 52-Week Placebo-Controlled Period of COAST-X Clinical nr-axSpA Trial3

IXE Q2W
N=102
n (%)

IXE Q4W
N=96
n (%)

PBO
N=104
n (%)

Injection site reaction (unspecified)

17 (16.7)b

11 (11.5)

4 (3.8)

Injection site erythema

4 (3.9)

3 (3.1)

1 (1.0)

Injection site swelling

2 (2.0)

2 (2.1)

0

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

aTEAEs 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.

bp<.001 vs PBO.

 In addition to the most commonly reported types of ISRs, as listed in Incidence of Injection Site Reactions During 52-Week Placebo-Controlled Period of COAST-X Clinical nr-axSpA Trial, injection site pain was reported in 1 patient (1.0%) each in the ixekizumab 80 mg Q2W and Q4W and placebo groups.3 

References

1Genovese MC, Kameda H, Rahman P, et al. Safety profile of ixekizumab in patients with moderate-to-severe plaque psoriasis and psoriatic arthritis: integrated analysis of 18 clinical trials. Poster presented at: American College of Rheumatology/ARP; November 8-13, 2019; Atlanta, GA.

2Shear NH, Paul C, Blauvelt A, et al. Safety and tolerability of ixekizumab: integrated analysis of injection-site reactions from 11 clinical trials. J Drugs Dermatol. 2018;17(2):200-206. http://jddonline.com/articles/dermatology/S1545961618P0200X

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

4Taltz [summary of product characteristics]. Eli Lilly and Company (Ireland) Limited, Ireland

5Griffiths 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.

6Griffiths CEM, Reich K, Gooderham M, et al. Long-term safety of ixekizumab in patients with moderate-to-severe psoriasis up to 5 years: pooled data from 16 clinical trials. Poster presented at: 29th Annual Meeting of the European Academy of Dermatology and Venereology (EADVirtual); October 29-31, 2020.

7Gordon 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

8Reich K, Leonardi C, Ohtsuki M, et al. Safety and tolerability of ixekizumab: integrated analysis of injection-site reactions in patients with moderate-to-severe psoriasis treated with ixekizumab compared with placebo or etanercept from three phase 3 trials. Poster presented at: 25th European Academy of Dermatology and Venereology Congress; September 28-October 2, 2016; Vienna, Austria.

9Sheth P, Muram T, Lin C, et al. Patient perspectives on injection site reactions in 2 phase 3 trials of ixekizumab versus etanercept and placebo in psoriasis. Poster presented at: 77th Annual Meeting of the American Academy of Dermatology; March 1-15, 2019; Washington, D.C.

10Schwartzman 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.

11Genovese MC, Mysler E, Tomita T, et al. Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials. Rheumatology (Oxford). 2020;59(12):3834-3844. https://doi.org/10.1093/rheumatology/keaa189

12Mease 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

13Nash 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

14Schwartzman S, Sandoval D, Kronbergs A, et al. Long-term safety profile of ixekizumab treatment on patients with axial spondyloarthritis. Poster presented at: Florida Society of Rheumatology 2021 Annual Meeting; July 9-11, 2021; Orlando, FL.

15Deodhar 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

16van 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

17Deodhar 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: 09 March 2022


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