Taltz ® (ixekizumab) injektion

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Taltz® (ixekizumab): Säkerhet och effekt vid behandling av AS/r-axSpA hos patienter med tidigare TNF-hämmare

I COAST-W var ixekizumab överlägsen placebo i det primära effektmåttet andelen patienter som fick ASAS40-svar vid vecka 16.

Summary

Ixekizumab is being studied for the treatment of AS/r-axSpA in 2 phase 3 double-blind, placebo-controlled trials.1,2

  • COAST-V (N=341) is a phase 3, 16-week double-blind, placebo-controlled trial with an active reference arm and an extension period to 52 weeks in patients with active AS/r-axSpA who are naive to bDMARDs.1

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

This response includes efficacy and safety information from a trial in patients with active AS/r-axSpA with an inadequate response or intolerance to at least 1, but no more than 2 TNF inhibitors (COAST-W).

In COAST-W, ixekizumab was superior to placebo in the primary outcome of the proportion of patients achieving an ASAS40 response at week 16. 

COAST-W Clinical Trial Data

Efficacy

The proportion of patients achieving an ASAS40 response (primary endpoint) and an ASAS20 response (secondary endpoint) in the ixekizumab 80 mg Q2W and Q4W, and placebo treatment groups at week 16 is shown below in Figure 1.

Figure 1. Proportion of Patients Achieving ASAS40 and ASAS20 Responses at Week 16 in COAST-W, NRI2,3

Abbreviations: ASAS = Assessment of Spondyloarthritis International Society; 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; NRI = nonresponder imputation; PBO = placebo.
*
p<.05 vs PBO.
p<.01 vs PBO.
ǂ
p<.001 vs PBO.

Safety

Most TEAEs for both ixekizumab 80 mg Q2W and Q4W dosing regimens were mild-to-moderate in severity. The frequency of TEAEs were similar for both ixekizumab dosing regimens.2

The most common TEAEs (defined as occurring in ≥5% of patients receiving ixekizumab) were upper respiratory tract infections and injection site reactions. Adverse events reported during the double-blind treatment period are summarized in Table 1.2

Table 1. Adverse Events During the Double-Blind Treatment Period of COAST-W2

 

PBO
N=104

IXE Q2W
N=98

IXE Q4W
N=114

TEAE

51 (49.0)

59 (60.2)

73 (64.0)

Mild

18 (17.3)

23 (23.5)

34 (29.8)

Moderate

26 (25.0)

32 (32.7)

35 (30.7)

Severe

7 (6.7)

4 (4.1)

4 (3.5)

Discontinuation due to AE

2 (1.9)

3 (3.1)

4 (3.5)

Serious AE

5 (4.8)

3 (3.1)

4 (3.5)

Deatha

1 (1.0)

0

Common TEAEsb

Upper respiratory tract infection

3 (2.9)

4 (4.1)

9 (7.9)

Injection site reaction

1 (1.0)

8 (8.2)

3 (2.6)

TEAEs of special interest

Hepatic 

2 (1.9)

1 (1.0)

5 (4.4)

Cytopenia

2 (2.0)

0

Grade 1 neutropeniac

1 (1.0)

8 (8.2)

10 (8.8)

Grade 2 neutropeniad

1 (1.0)

1 (0.9)

Grade 3 neutropeniae

0

0

0

Grade 4 neutropeniaf

0

0

1 (0.9)

Infections

10 (9.6)

23 (23.5)

34 (29.8)

Mild

5 (4.8)

14 (14.3)

20 (17.5)

Moderate

5 (4.8)

9 (9.2)

13 (11.4)

Severe

0

0

1 (0.9)

Serious

0

0

2 (1.8)

Candida (genital)

1 (1.0)

0

Candida (esophageal)

1 (1.0)

0

Herpes zoster

0

0

1 (0.9)

Reactivated TB

0

0

0

Allergic reactions/hypersensitivities

1 (1.0)

6 (6.1)

3 (2.6)

Potential anaphylaxis

0

0

0

Injection site reactionsg

6 (5.8)

16 (16.3)

9 (7.9)

Cerebrocardiovascular eventsh

1 (1.0)

1 (1.0)

0

Malignancies

0

0

1 (0.9)

Depression

5 (4.8)

2 (2.0)

0

Anterior uveitisi

0

3 (3.1)

2 (1.8)

Inflammatory bowel disease

1 (1.0)

0

3 (2.6)

Interstitial lung disease

0

0

0

Abbreviations: AE = adverse event; 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; TB = tuberculosis; TEAE = treatment-emergent adverse event.

a Cause of death was suicide. The event was judged by the blinded principal investigator to be unrelated to the investigational product. The patient had a documented prior history of depression of about 1 year (reported as mild at study entry).

b Common TEAEs defined as those that occurred at a frequency of ≥5% for patients receiving ixekizumab (both treatment groups combined).

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

d ≥1.0 to <1.5 x 109 cells/L.

e ≥0.5 to <1.0 x 109 cells/L.

f <0.5 x 109 cells/L.

g Injection site reactions high level term includes injection site pain, erythema, dermatitis, hypersensitivity, pruritus, bruising, rash, paresthesia, or reaction (unspecified).

h Confirmed events only.

i Not a prespecified AE of special interest but included in prespecified analyses.

Note that multiple, different dosing regimens, including unapproved doses, are included in this response. Please refer to the Taltz Summary of Product Characteristics for approved dosing.

References

1. 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

2. 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

3. Deodhar AA, Poddubnyy D, Pacheco-Tena C, et al. Efficacy and safety of ixekizumab in the treatment of radiographic axial spondyloarthritis: 16-week results of a phase 3 randomized, double-blind, placebo-controlled trial in patients with prior inadequate response or intolerance to 1 or 2 tumor necrosis factor inhibitors. Poster presented at: American College of Rheumatology/ARHP; October 19-24, 2018; Chicago, IL.

Glossary

ASAS = Assessment of SpondyloArthritis international Society

ASAS20 = improvement of ≥20% and ≥1 unit in ≥3 ASAS domains, with no deterioration of ≥20% and ≥1 unit in the potential remaining domain

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

bDMARD = biologic disease-modifying antirheumatic drug

Q2W = every 2 weeks

Q4W = every 4 weeks

TEAE = treatment-emergent adverse event

TNF = tumor necrosis factor

Datum fӧr senaste ӧversyn 2019 M02 04


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