Taltz ® (ixekizumab) injection

80 mg/mL

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

The majority of cases of neutropenia reported with Taltz (ixekizumab) were either grade 1 or grade 2. In general, neutropenia was transient, did not require discontinuation of ixekizumab, and was not associated with an increased frequency of infections.

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en-US

Ixekizumab Prescribing Information Related to Neutropenia

The incidences of treatment-emergent neutropenia from the prescribing information are listed in Neutropenia Grade 1, Grade 2, > Grade 3 Through Week 12 of UNCOVER Psoriasis Clinical Trials and Neutropenia Incidence Weeks 0 Through 60 of UNCOVER Psoriasis Clinical Trials. These data are from the UNCOVER clinical trials that were conducted in adult patients with moderate-to-severe plaque psoriasis.1

  • The majority of cases of neutropenia were either grade 1 or grade 2.1
  • In patients treated with ixekizumab, the incidence rate of neutropenia during weeks 13 to 60 was lower than the incidence rate during weeks 0 to 12.1
  • Neutropenia in the ixekizumab group was not associated with an increased rate of infection compared with the placebo group.1
Neutropenia Grade 1, Grade 2, > Grade 3 Through Week 12 of UNCOVER Psoriasis Clinical Trials1

Neutropenia

Ixekizumab Q2W

Placebo

Grade 1a

7%

3%

Grade 2b

2%

0.3%

Grade ≥3c

0.2%d

0.1%e

Abbreviation: Q2W = ixekizumab 80 mg every 2 weeks following a 160-mg starting dose.

aGrade 1 neutropenia defined as >1500 to <2000 cells/mm3.

bGrade 2 neutropenia defined as >1000 to <1500 cells/mm3.

cGrade >3 neutropenia defined as <1,000 cells/mm3.

dCorresponds to 0.007 events per subject-year of follow-up.

eCorresponds to 0.006 events per subject-year of follow-up.

Neutropenia Incidence Weeks 0 Through 60 of UNCOVER Psoriasis Clinical Trials1

Neutropenia

Ixekizumab

Placebo

All Grades

11%a

3%b

aCorresponds to 0.24 events per subject-year of follow-up.

bCorresponds to 0.14 events per subject-year of follow-up.

Clinical Trial Laboratory Assessment of Neutropenia Results

Psoriasis

UNCOVER-1, -2, and -3 Pivotal Trials

Neutropenia Laboratory Assessments Across the 3 UNCOVER Psoriasis Clinical Trials Combined shows the number of patients with reductions in neutrophil counts from normal levels in the 3 UNCOVER psoriasis clinical studies.

The results reflect all patients with at least 1 postbaseline value for neutrophil level across all 3 pivotal UNCOVER clinical trials combined. Results are included for weeks 0 to 12 and weeks 0 to 60.2,3

Neutropeniaa Laboratory Assessments Across the 3 UNCOVER Psoriasis Clinical Trials Combined2,3

 

Weeks 0-12

Weeks 0-60

IXE Q2W
(N=1167; Nx=1163)

IXE Q4W
(N=1161; Nx=1152)

PBO
(N=791; Nx=787)

All Ixekizumab Exposuresb
(N=3736; Nx=3716)

Grades 1-4 combined, n (%)

108 (9.3)

99 (8.6)

26 (3.3)

428 (11.5)

Grade 1c neutropenia, n (%)

81 (7.0)

76 (6.6)

23 (2.9)

321 (8.6)

Grade 2d neutropenia, n (%)

25 (2.1)

22 (1.9)

2 (0.3)

97 (2.6)

Grade 3e neutropenia, n (%)

2 (0.2)

0

1 (0.1)

8 (0.2)

Grade 4f neutropenia, n (%)

0

1 (0.1)g

0

2 (0.1)

Abbreviations: IXE Q2W = ixekizumab 80 mg every 2 weeks following 160 mg starting dose; IXE Q4W = ixekizumab 80 mg every 4 weeks following 160 mg starting dose; n = number of patients who experienced respective neutropenia events; N = total number of patients in each analysis group; Nx = number of evaluable patients in each analysis group (ie, patients with at least 1 postbaseline neutropenia value); PBO = placebo.
Note: % reflects n/Nx (number of patients who experienced respective neutropenia events/number of evaluable patients in each analysis group).

aNeutropenia data include patients with postbaseline neutrophil counts that worsened from a normal level or from the grade at baseline.

bConsists of all patients who received ixekizumab at any point through week 60 including those patients initially randomized to IXE Q2W, IXE Q4W, and PBO across all 3 studies and patients initially randomized to etanercept (N=740) in UNCOVER-2 and UNCOVER-3. Trial design details are available upon request.

cGrade 1 neutropenia defined as ≥1500 to <2000 cells/mm3.

dGrade 2 neutropenia defined as ≥1000 to <1500 cells/mm3.

eGrade 3 neutropenia defined as ≥500 to <1000 cells/mm3.

fGrade 4 neutropenia defined as <500 cells/mm3.

gIn patient with grade 4 neutropenia, neutrophil count was within normal range in a 2-day retest.

All Psoriasis Ixekizumab Exposures Integrated Analysis

An integrated safety analysis was conducted from all ixekizumab adult psoriasis exposures (N=6892; 18,025.7 patient-years [PYs] of exposure) across 17 clinical trials with data up to March 19, 2021. Neutropenia grade ≥3 (<1000 cells/mm3) was reported in 29 (0.4%) patients (IR=0.2 per 100 PYs of exposure).4

Psoriatic Arthritis

SPIRIT-P1 and -P2 Double-Blind Treatment Periods

Neutropenia Laboratory Assessments Through Week 24 of SPIRIT-P1 and SPIRIT-P2 Psoriatic Arthritis Clinical Trials shows the number of patients with reductions in neutrophil counts from normal levels in the SPIRIT-P1 and -P2 clinical studies.

From the 24-week double-blind treatment periods of both SPIRIT-P1 and -P2 studies

Neutropenia Laboratory Assessments Through Week 24 of SPIRIT-P1 and SPIRIT-P2 Psoriatic Arthritis Clinical Trials5,6

SPIRIT-P1

SPIRIT-P2

Total Ixekizumab
(N=209; Nx=209)

Total Ixekizumab
(N=245; Nx=244)

Grades combined, n (%)

23 (11.0)

22 (9.0)

Grade 1a neutropenia, n (%)

13 (6.2)

19 (7.8)

Grade 2bc neutropenia, n (%)

10d (4.8)

3 (1.2)

Abbreviations: n = number of patients who experienced respective neutropenia events; N = total number of patients in each analysis group; Nx = number of evaluable patients in each analysis group (ie, patients with at least 1 postbaseline neutropenia value).
Note: % reflects n/Nx (number of patients who experienced respective neutropenia events/number of evaluable patients in each analysis group). 
Note: There were no instances of grade 3 (≥500 to <1000 cells/mm3) or grade 4 (<500 cells/mm3) neutropenia in either SPIRIT-P1 or SPIRIT-P2.

aGrade 1 neutropenia defined as ≥1500 to <2000 cells/mm3.

bGrade 2 neutropenia defined as ≥1000 to <1500 cells/mm3.

cNo infection onset occurred within 14 days of any report of grade 2 neutropenia in either SPIRIT-P1 or SPIRIT-P2.

dOne patient had grade 2 neutropenia on more than 1 assessment in SPIRIT-P1.

SPIRIT-P1 and -P2 Extension Periods

In the SPIRIT-P1 (up to 52 weeks) and SPIRIT-P2 (up to 52 weeks) extension periods of treatment with ixekizumab, all cases of treatment-emergent neutropenia were either grade 1 or grade 2. There were no laboratory parameters of absolute neutropenia shifts from normal to grade 3 or higher.7,8

All Psoriatic Arthritis Ixekizumab Exposures Integrated Analysis

An integrated safety analysis was conducted from all ixekizumab psoriatic arthritis exposures (N=1401; 2247.7 PYs of exposure) across 4 clinical trials with data up to March 19, 2021. Neutropenia grade ≥3 (<1000 cells/mm3) was reported in 8 (0.6%) patients (IR=0.4 per 100 PYs of exposure).9

Axial Spondyloarthritis

Ankylosing Spondylitis/Radiographic Axial Spondyloarthritis Trials

COAST-V and COAST-W Double-Blinded Treatment Periods

Treatment-Emergent Neutropenia During the Double-Blind Treatment Period of COAST-V and COAST-W  shows the incidence of treatment-emergent neutropenia during the double-blind periods of COAST-V and COAST-W.

In COAST-V and COAST-W, mild neutropenia (grade 1) was reported more often in the ixekizumab groups than in the placebo group.10,11 The cases of grade 1 neutropenia were transient in nature and resolved without discontinuation of ixekizumab.10,12 

Treatment-Emergent Neutropenia During the Double-Blind Treatment Period of COAST-V and COAST-W10,11 

Event

COAST-V

COAST-W

PBO
(N=86)
n (%)

ADA Q2W
(N=90)
n (%)

IXE Q2W
(N=83)
n (%)

IXE Q4W
(N=81)
n (%)

PBO
(N=104)
n (%)

IXE Q2W
(N=98)
n (%)

IXE Q4W
(N=114)
n (%)

Grade 1a neutropenia

2 (2)

18 (20)

8 (10)

6 (8)

1 (1)

8 (8)

10 (9)

Grade 2b neutropenia

1 (1)

3 (3)

3 (4)

2 (3)

0

1 (1)

1 (1)

Grade 3c neutropenia

0

1 (1)

0

0

0

0

0

Grade 4d neutropenia

0

0

0

0

0

0

1 (1)e

 Abbreviations: ADA Q2W = adalimumab 40 mg every 2 weeks; 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 or 80 mg starting dose; PBO = placebo.

aGrade 1 neutropenia defined as ≥1.5 to <2.0 × 109 cells/L.

bGrade 2 neutropenia defined as ≥1.0 to <1.5 × 109 cells/L.

cGrade 3 neutropenia defined as ≥0.5 to <1.0 × 109 cells/L.

dGrade 4 neutropenia defined as <0.5 × 109 cells/L.

eThe patient was diagnosed with acute promyelocytic leukemia 4 weeks postbaseline. A post-hoc analysis of a serum sample collected prior to study entry identified a genetic risk factor for acute promyelocytic leukemia. The patient discontinued from the study.

COAST-V and COAST-W Dose Double-Blind Extension Period

During the dose double-blinded extended treatment period of COAST-V and COAST-W (weeks 16-52), no patients reported a treatment-emergent adverse event (TEAE) of grade 3 or 4 neutropenia. The pooled incidence rate of grade 3 or 4 neutropenia was 0.2 per 100 PYs for weeks 0-52.13

Nonradiographic Axial Spondyloarthritis Trials

COAST-X 52-Week Double-Blinded Treatment Period

During the double-blinded treatment period of COAST-X, a TEAE of grade 3 or 4 neutropenia was not reported in patients treated with ixekizumab. Grade 4 neutropenia was reported in one patient in the placebo group (Treatment-Emergent Neutropenia Through the 52-week Double-Blinded Treatment Period of COAST-X).14

Treatment-Emergent Neutropenia Through the 52-week Double-Blinded Treatment Period of COAST-X14

Event  

PBO
(N=104)
n (%)

IXE Q4W
(N=96)
n (%)

IXE Q2W
(N=102)
n (%)

Grade 1a neutropenia

8 (8)

11 (11)

13 (13)

Grade 2b neutropenia

0

1 (1)

2 (2)

Grade 3c neutropenia

0

0

0

Grade 4d neutropenia

1 (1)

0

0

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

aGrade 1 neutropenia defined as ≥1.5 to <2.0 x 109 cells/L.

bGrade 2 neutropenia defined as ≥1.0 to <1.5 x 109 cells/L.

cGrade 3 neutropenia defined as ≥0.5 to <1.0 x 109 cells/L.

dGrade 4 neutropenia defined as <0.5 x 109 cells/L.

All Axial Spondyloarthritis Ixekizumab Exposures Integrated Analysis

An integrated safety analysis was conducted from all ixekizumab axial spondyloarthritis exposures (N=932; 2096.2 PYs of exposure) across 4 trials (including ankylosing spondylitis/radiographic axial spondyloarthritis and nonradiographic axial spondyloarthritis) with data up to March 19, 2021. Neutropenia grade ≥3 (<1000 cells/mm3) was reported in 4 (0.4%) patients (IR=0.2 per 100 PYs of exposure).9

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; 2021.

2Strober B, Pangallo B, Veenhizen M, et al. Safety and tolerability of ixekizumab: analysis of neutropenia in 7 clinical studies of moderate-to-severe plaque psoriasis. Poster presented at: 24th European Academy of Dermatology and Venereology Congress; October 7-11, 2015; Copenhagen, Denmark.

3Gordon 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

4Griffiths 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.

5Mease 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

6Nash 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

7Mease PJ, Okada M, Kishimoto M, et al. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis: 52-week results from a phase 3 study (SPIRIT P1). Abstract presented at: European League Against Rheumatism (EULAR) Congress; June 8-11, 2016; London, England.

8Genovese MC, Combe B, Kremer JM, et al. Safety and efficacy of ixekizumab in patients with PsA and previous inadequate response to TNF inhibitors: week 52 results from SPIRIT-P2. Rheumatology. 2018;57(11):2001-2011. http://dx.doi.org/10.1093/rheumatology/key182

9Schwartzman 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.

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

11van 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

12Data on file, Eli Lilly and Company and/or one of its subsidiaries.

13Dougados M, Cheng-Chung Wei J, Landewé R, et al; COAST-V and COAST-W Study Groups. Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W). Ann Rheum Dis. 2020;79(2):176-185. http://dx.doi.org/10.1136/annrheumdis-2019-216118

14Deodhar 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: March 16, 2022


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