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)

Taltz® ▼ (ixekizumab): Long Term Safety in Axial Spondyloarthritis

Reported TEAEs in patients exposed to ixekizumab in axial spondyloarthritis clinical trials through April 2019 are shown in this response.

Safety Results for Double-Blind Treatment Periods of Axial Spondyloarthritis Trials

Note: The below mentioned dosing schedule IXE Q2W is not cosistent with the approved dosing schedule for axial spondyloarthritis. Please refer to the Taltz Summary of Product Characteristics for approved dosing.1

COAST-V

Most TEAEs for both ixekizumab Q2W and ixekizumab Q4W dosing regimens were mild-to-moderate in severity. The frequencies of TEAEs were similar for both ixekizumab dosing regimens.2

COAST-W

Most TEAEs for both ixekizumab 80 mg Q2W and Q4W dosing regimens were mild-to-moderate in severity. The frequencies of TEAEs were similar for both ixekizumab dosing regimens.3

COAST-X

Most TEAEs for both ixekizumab 80 mg Q2W and Q4W dosing regimens were mild-to-moderate in severity. The frequencies of TEAEs were similar for both ixekizumab dosing regimens.4

Integrated Safety Analysis of Axial Spondyloarthritis Trials

Overview

An integrated analysis of data through April 2019 from COAST-V, COAST-W, COAST-X, and COAST-Y axSpA trials (including AS/r-axSpA and nr-axSpA) evaluated the safety of ixekizumab in 929 patients accounting for 1336.2 PYs of exposure with axSpA and includes exposures up to 2 years. Overall, 747 patients (IR 55.9 per 100 PYs; 95% CI, 52.0-60.1) reported at least one TEAE. Of these events,

  • 306 (IR, 22.9; 95% CI, 20.5-25.6) were mild

  • 358 (IR, 26.8; 95% CI, 24.2-29.7) were moderate, and

  • 83 (IR, 6.2; 95% CI, 5.0-7.7) were severe.5

A total of 74 patients (IR, 5.5 per 100 PY; 95% CI, 4.4-7.0) reported at least 1 SAE and 52 patients (IR, 3.9 per 100 PY; 95% CI, 3.0-5.1) discontinued from the study due to an AE.5

One death in a patient who received ixekizumab was reported due to suicide. The patient had a prior history of mild depression, and the suicide was not considered to be related to study drug. One death in a patient who received ixekizumab was reported due to murder.5

The most commonly-reported TEAEs were

  • nasopharyngitis, n=147 (IR, 11.0; 95% CI, 9.4-12.9)

  • upper respiratory tract infection, n=98 (IR, 7.3; 95% CI, 6.0-8.9)

  • unspecified injection site reaction, n=91 (IR, 6.8; 95% CI, 5.5-8.4), and

  • headache, n=31 (IR, 2.3; 95% CI, 1.6-3.3).5

Infections

The IRs of infections in the long-term integrated safety analysis of 4 axSpA trials are presented in Table 1.

Infections with an IR ≥2 were

  • nasopharyngitis, n=147 (IR, 11.0; 95% CI, 9.4-12.9)

  • upper respiratory tract infection, n=98 (IR, 7.3; 95% CI, 6.0-8.9)

  • bronchitis, n=55 (IR, 4.1; 95% CI, 3.2-5.4)

  • pharyngitis, n=51 (IR, 3.8; 95% CI, 2.9-5.0)

  • sinusitis, n=30 (IR, 2.2; 95% CI, 1.6-3.2), and 

  • urinary tract infection, n=30 (IR=2.2; 95% CI, 1.6-3.2).5,6

There were no confirmed cases of tuberculosis reactivation and no cases of positive tuberculosis seroconversion.5

Table 1. Incidence of Infection in the Longer-Term Integrated Safety Analysis From axSpA Trials (COAST-V, -W, -X, and -Y) as of April 20195

 

Number of Events
(N=929; PY=1336.2)

IR (95% CI)

Infections

478

35.8 (32.7-39.1)

Serious Infections

17

1.3 (0.8-2.0)

Opportunistic Infections

23

1.7 (1.1-2.6)

Candida

22

1.6 (1.1-2.5)

Herpes zoster

11

0.8 (0.5-1.5)

Latent tuberculosisa

1

0.1 (0.0-0.5)

Abbreviations: axSpA = axial spondyloarthritis; IFN = interferon; IR = incidence rate per 100 patient-years; PY = patient-years; TB = tuberculosis.

a Includes cases positive for any of the following: tuberculin skin test, IFN-gamma release assay, history of TB, completed TB treatments.

Other Adverse Events of Special Interest

The IRs of AEs of special interest in the long-term integrated safety analysis from axSpA trials COAST-V, -W, -X, and -Y are presented in Table 2.

 

Table 2. Adverse Events of Special Interest in the Long-Term Integrated Safety Analysis of axSpA Trials (COAST-V, -W, -X, and -Y)5

Adverse Event

Number of Events
(N=929; PY=1336.2)

IR (95% CI)

Injection site reactions

154

11.5 (9.8-13.5)

Hypersensitivity/allergic reactions

74

5.5 (4.4-7.0)

Major Adverse Cerebrocardiovascular Events (adjudicated)

2a

0.1 (0.0-0.6)

Malignancies

6b

0.4 (0.2-1.0)

Depression

13

1.0 (0.6-1.7)

Suicidal behavior/self-injury

2

0.1 (0.0-0.6)

Cytopenia

23c

1.7 (1.1-2.6)

Inflammatory Bowel Disease (adjudicated)

13d

1.0 (0.6-1.7)

Crohn's disease

7

0.5 (0.2-1.1)

Ulcerative colitis

6

0.4 (0.2-1.0)

Iritis

6

0.4 (0.2-1.0)

Iridocyclitis

42

3.1 (2.3-4.3)

Abbreviations: axSpA = axial spondyloarthritis; IBD = inflammatory bowel disease; IR = incidence rate per 100 patient-years; MedDRA = Medical Dictionary for Regulatory Activities; PY = patient-years; UC = ulcerative colitis.

a Both cases were nonfatal myocardial infarction.

b Ovarian cancer, acute promyelocytic leukemia, anal cancer, bladder cancer, breast cancer, chronic lymphocytic leukemia.

c Broad, according to Standard MedDRA Query classification.

d The data represents adjudicated cases. Events classified as ‘definite’ and ‘probable’ per external adjudication are included when determining IR and were considered positively adjudicated. IR was calculated as the total of ‘definite’ and ‘probable’ cases/total patient-years, then multiplied by 100. In the axSpA program, one patient event of UC was reported in placebo group and later adjudicated as Crohn's disease; and another placebo patient with history of ulcerative colitis had reported event of ulcerative colitis but was later adjudicated as insufficient information.

Change in Incidence of Adverse Events Over Time

In a long-term integrated safety analysis of COAST-V, COAST-W, COAST-X, and COAST-Y trials in axSpA (including AS/r-axSpA and nr-axSpA) patients as of April 2019,

  • the IRs for TEAEs, SAEs, infections, and injection site reactions decreased over time, and

  • the IRs for inflammatory bowel disease, malignancy, and serious infections were low and did not increase over time.5

Clinical Trials of Ixekizumab for the Treatment of Axial Spondyloarthritis Brief Descriptions

COAST-V (N=341) is a phase 3, 16-week double-blind, placebo-controlled trial with an active reference arm and a dose double-blind extension period to 52 weeks in patients with active AS/r-axSpA who are naive to bDMARDs.2

COAST-W (N=316) is a phase 3, 16-week double-blind, placebo-controlled trial with a dose double-blind extension period to 52 weeks in patients with active AS/r-axSpA and an inadequate response or intolerance to 1 or 2 TNF inhibitors.3

COAST-X (N=303) is a phase 3, 52-week double-blind, placebo-controlled trial in patients with nr-axSpA who are naive to bDMARDs.4

COAST-Y (N=750) is a phase 3, 104-week, long-term extension trial including a double-blind, placebo-controlled 40-week randomized withdrawal-retreatment period in patients with axial spondyloarthritis who have completed the final study visit in COAST-V, COAST-W, or COAST-X.7

References

1. Taltz [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2. van der Heijde D, Cheng-Chung Wei J, Dougados M, et al. 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

3. Deodhar A, Poddubnyy D, Pacheco-Tena C, et al. 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

4. Deodhar A, van der Heijde D, Gensler LS, et al. 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

5. Genovese 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). Published online May 25, 2020. https://doi.org/10.1093/rheumatology/keaa189

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

7. A Long Term Extension Study of Ixekizumab (LY2439821) in Participants With Axial Spondyloarthritis. ClinicalTrials.gov identifier: NCT031129100. Updated May 3, 2019. Accessed June 24, 2019. https://www.clinicaltrials.gov/ct2/show/NCT03129100

Glossary

AE = adverse event

ASAS40 = improvement of ≥40% and ≥2 units in ≥3 ASAS domains, with no deterioration in the potential remaining domain

AS/r-axSpA = ankylosing spondylitis/radiographic axial spondyloarthritis

axSpA = axial spondyloarthritis

bDMARD = biologic disease-modifying antirheumatic drug

IR = incidence rate

nr-axSpA = nonradiographic axial spondyloarthritis

PY = patient-years

Q2W = every 2 weeks

Q4W = every 4 weeks

SAE = serious adverse event

TEAE = treatment-emergent adverse event

TNF = tumor necrosis factor

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Date of Last Review: July 19, 2020


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