Taltz ® (ixekizumab)

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Taltz® (ixekizumab): What is the Long-Term Safety in Axial Spondyloarthritis?

Overall, the long-term safety profile of ixekizumab was consistent with what has been previously reported and no new safety signals were identified.

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Integrated Safety Analysis of Axial Spondyloarthritis Trials

The safety analysis in this response included data from all patients who received at least 1 dose of ixekizumab from week 0 of the originating trials COAST-V, COAST-W, and COAST-X (each trial lasting 52 weeks) and up to week 104 of the long-term extension trial COAST-Y. The analysis evaluated the safety of ixekizumab in 932 patients accounting for 2097.7 patient-years (PYs) of exposure.1

Overall, the long-term safety profile of ixekizumab was consistent with what has been previously reported and no new safety signals were identified. Most treatment-emergent adverse events (TEAEs) were mild or moderate in severity (Summary of Adverse Events in the Long-Term Integrated Safety Analysis of axSpA Trials (COAST-V, -W, -X, and -Y)).

A total of 101 patients (10.8%; IR 4.8 per 100 PYs) reported at least 1 serious adverse event and 66 patients (7.1%; IR 3.1 per 100 PYs) discontinued from the study because of an adverse event.1

Three reported deaths in patients who received ixekizumab were due to

  • suicide (the patient had a prior history of mild depression, and the suicide was not considered to be related to study drug by the investigator)1,2
  • murder, and
  • sepsis (reported in a patient with a history of chronic renal failure and atrial fibrillation).1
Summary of Adverse Events in the Long-Term Integrated Safety Analysis of axSpA Trials (COAST-V, -W, -X, and -Y)1

Treatment-Emergent Adverse Eventa

IXE Q4W
(N=454; 878.2 PYs)b
n (%) [IR]

IXE Q2W
(N=604; 1219.5 PYs)b
n (%) [IR]

TEAE

380 (83.7) [43.3]

462 (76.5) [37.9]

Mild

141 (31.1) [16.1]

161 (26.7) [13.2]

Moderate

198 (43.6) [22.5]

238 (39.4) [19.5]

Severe

41 (9.0) [4.7]

63 (10.4) [5.2]

Infections

248 (54.6) [28.2]

309 (51.2) [25.3]

Serious infections

9 (2.0) [1.0]

14 (2.3) [1.1]

Serious adverse event

44 (9.7) [5.0]

57 (9.4) (4.7)

Discontinuation due to AE

26 (5.7) [3.0]

40 (6.6) [3.3]

Injection site reactions

53 (11.7) [6.0]

107 (17.7) [8.8]

Hypersensitivity/allergic reactions

39 (8.6) [4.4]

52 (8.6) [4.3]

Potential anaphylaxis

0

1 (0.2) [0.1]c

Cerebrocardiovascular events

8 (1.8) [0.9]

10 (1.7) [0.8]

MACEd

2 (0.4) [0.2]

4 (0.7) [0.3]

Anterior uveitis

28 (6.2) [3.2]

30 (5.0) [2.5]

With history

18 (4.0) [2.0]

23 (3.8) [1.9]

Without history

10 (2.2) [1.1]

7 (1.2) [0.6]

Malignancies

3 (0.7) [0.3]

6 (1.0) [0.5]

Depression

6 (1.3) [0.7]

13 (2.2) [1.1]

Cytopenias

8 (1.8) [0.9]

21 (3.5) [1.7]

Neutropenia

4 (0.9) [0.5]

9 (1.5) [0.7]

IBD (adjudicated)e

11 (2.4) [1.3]

6 (1.0) [0.5]

Crohn's disease

5 (1.1) [0.6]

2 (0.3) [0.2]

Ulcerative colitis

6 (1.3) [0.7]

4 (0.7) [0.3]

Abbreviations: AE = adverse event; axSpA = axial spondyloarthritis; IBD = inflammatory bowel disease; IR = incidence rate per 100 patient-years; MACE = major adverse cerebrocardiovascular event; PYs = patient-years; Q2W = every 2 weeks; Q4W = every 4 weeks; TEAE = treatment-emergent adverse event.

aIncludes data from all patients who received at least 1 dose of ixekizumab since week 0 of the originating trials COAST-V, COAST-W, and COAST-X up to week 104 of a long-term extension trial COAST-Y.

bDuring COAST-X, 40 patients switched from IXE Q4W to Q2W and COAST-Y had 86 patients escalated from IXE Q4W to IXE Q2W. Data while patients were on IXE Q4W are reported in the IXE Q4W group; data while patients were on IXE Q2W are reported in the IXE Q2W group. These 126 patients were counted in both IXE Q4W and IXE Q2W but only counted once in total IXE.

cPotential case of anaphylaxis (not confirmed).

dMACE cases include confirmed cases of vascular death (including cardiovascular and cerebrovascular deaths and excluding hemorrhagic deaths outside of the central nervous system), nonfatal myocardial infarction, and nonfatal stroke.

eOf the 17 IBD cases that were confirmed by adjudication, 5 patients had a history of IBD (1 Crohn’s disease and 4 ulcerative colitis); 2 additional cases of IBD reported, 1 case during the long-term extension period (weeks 64-104) and 1 case during the posttreatment follow-up period.

Brief Safety Results for Placebo-Controlled Treatment Periods of Axial Spondyloarthritis Trials

Note: The dosing schedule IXE Q2W is not consistent with the approved dosing schedule for axial spondyloarthritis. Please refer to the Taltz Summary of Product Characteristics for approved dosing.3

COAST-V

COAST-V (N=341) was a phase 3, 16-week double-blind, placebo-controlled trial with an active reference arm and a dose double-blind extension period of 52 weeks, conducted in patients with active ankylosing spondylitis/radiographic axial spondyloarthritis (AS/r-axSpA) who were naïve to biologic disease-modifying antirheumatic drugs (bDMARDs).4

Most TEAEs for both ixekizumab every 2 weeks (Q2W) and ixekizumab every 4 weeks (Q4W) dosing regimens were mild-to-moderate in severity. The frequencies of TEAEs were similar for both ixekizumab dosing regimens.4

COAST-W

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

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.2

COAST-X

COAST-X (N=303) was a phase 3, 52-week double-blind, placebo-controlled trial, conducted in patients with nr-axSpA who were naïve to bDMARDs.5

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.5

COAST-Y Extension Trial

COAST-Y (N=773) was a phase 3, 104-week, long-term extension trial that included a double-blind, placebo-controlled 40-week randomized withdrawal-retreatment period, conducted in patients with axial spondyloarthritis who completed the final study visit in COAST-V, COAST-W, or COAST-X trials.6

References

1Deodhar A, Poddubnyy D, Rahman P, et al. Safety and efficacy of ixekizumab treatment in patients with axial spondyloarthritis: 3-year clinical trial results from the COAST program. Poster presented at: European League Against Rheumatism (EULAR); June 1-4, 2022.

2Deodhar 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

3Taltz [summary of product characteristics]. Eli Lilly and Company (Ireland) Limited, Ireland

4van 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

5Deodhar 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

6A long term extension study of ixekizumab (LY2439821) in participants with axial spondyloarthritis. ClinicalTrials.gov identifier: NCT03129100. Updated June 13, 2022. Accessed June 28, 2022. https://www.clinicaltrials.gov/ct2/show/NCT03129100

Date of Last Review: 13 July 2022


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