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): How to proceed after a missed starting dose?

The decision regarding how to proceed following a missed starting dose should be made by the prescribing physician. Information on the starting doses in the clinical trials are available in this response.

Summary

  • Lilly has not conducted any studies to evaluate the efficacy and safety of an additional 80 mg dose in patients who received 80 mg as the initial dose rather than the recommended 160 mg.

  • The starting doses 160 mg versus 80 mg has been studied in phase 3 AS/r-axSpA and nr-axSpA trials and information are available in Starting Dose in AS/r-axSpA Clinical Trials and Starting Dose in the Nonradiographic Axial Spondyloarthritis Clinical Trial.

  • No clinical trials of ixekizumab in patients with moderate-to-severe plaque psoriasis or active psoriatic arthritis have directly compared administration with and without a 160 mg starting dose with regards to the pharmacokinetics, efficacy, or safety of ixekizumab.

  • In the following sections are dosing schedules included that are not consistent with the approved dosing schedules. Please refer to Approved Dosing Regimens for approved dosing.

Starting Dose in AS/r-axSpA Clinical Trials

In the 2 phase 3 clinical trials in AS/r-axSpA, COAST-V, and COAST-W, patients were randomized to receive a starting dose of either 160 mg or 80 mg followed by 80 mg Q4W or 80 mg Q2W.1,2

In COAST-V and COAST-W, the week 0 starting dose of 160 mg vs 80 mg did not lead to any meaningful differences in the clinical results observed at week 16.1,2

The time course of ASAS20 and ASAS40 response rates up to week 16 by starting dose is shown in Figure 1.

Figure 1. Time Course of ASAS20 and ASAS40 Response Rate Through Week 16 by Starting Dose (Integrated COAST-V and COAST-W)3

Abbreviations: ASAS40 = improvement of ≥40% and ≥2 units in ≥3 ASAS domains, with no deterioration in the potential remaining domain; ASAS20 = improvement of ≥20% and ≥1 unit in ≥3 ASAS domains, with no deterioration of ≥20% and ≥1 unit in the potential remaining domain; IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; PBO = placebo; 80S = 80 mg starting dose; 160S = 160 mg starting dose.

Notes: Data is from an integrated analysis of the COAST-V and COAST-W clinical trials using nonresponder imputation in the intent-to-treat population.

In the weeks following initiation of treatment in COAST-V and COAST-W, higher ixekizumab concentrations were achieved with the 160 mg starting dose compared with the 80 mg starting dose; however, this did not translate into a significant effect on the predicted ASAS20 and ASAS40 responses in the pharmacokinetic and pharmacodynamic exposure-response models at week 16.3

See Table 1 below for ASAS20 and ASAS40 response rates at weeks 1 and 2 by ixekizumab starting dose. 

Table 1. ASAS20 and ASAS40 Response Rates at Weeks 1 and 2 by Ixekizumab Starting Dose, NRI (Integrated COAST-V and COAST-W)1-3

Response Parameter

ASAS20

ASAS20

ASAS20

ASAS20

ASAS40

ASAS40

ASAS40

ASAS40

Dosing Regimen

IXE Q4W

IXE Q4W

IXE Q2W

IXE Q2W

IXE Q4W

IXE Q4W

IXE Q2W

IXE Q2W

Starting Dose

80 mg
n=102

160 mg
n=93

80 mg
n=93

160 mg
n=88

80 mg
n=102

160 mg
n=93

80 mg
n=93

160 mg
n=88

Week 1, n (%)

28 (27.5)

27 (29.0)

30 (32.3)

21 (23.9)

11 (10.8)

8 (8.6)

14 (15.1)

10 (11.4)

Week 2, n (%)

39 (38.2)

38 (40.9)

41 (44.1)

24 (27.3)a

15 (14.7)

16 (17.2)

17 (18.3)

13 (14.8)

Abbreviations: ASAS40 = improvement of ≥40% and ≥2 units in ≥3 ASAS domains, with no deterioration in the potential remaining domain; ASAS20 = improvement of ≥20% and ≥1 unit in ≥3 ASAS domains, with no deterioration of ≥20% and ≥1 unit in the potential remaining domain; 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.

a p=.023 vs IXE Q2W 80 mg starting dose.

For a variety of clinically important endpoints across key domains of the disease in TNF inhibitor-experienced patients (COAST-W), the 160 mg starting dose consistently showed numerically improved efficacy at early time points relative to the 80 mg starting dose.3

Evaluation of the effect of starting dose on speed of onset requires further analyses.1

Starting Dose in the Nonradiographic Axial Spondyloarthritis Clinical Trial

In the COAST-X trial in nr-axSpA, patients were randomized to receive a starting dose of either 160 mg or 80 mg followed by 80 mg Q4W or 80 mg Q2W.4

The week 0 starting dose of 160 mg vs 80 mg did not affect the primary outcome results of ASAS40 response at week 16 or 52.4 The time course of ASAS40 response rates up to week 52 by starting dose is shown in Figure 2.

Figure 2. ASAS40 Response Rate Through Week 52 of COAST-X by Ixekizumab Starting Dose, NRI, ITT Population, Prior to any Switch to Open-label IXE Q2W3

Abbreviations: ASAS40 = improvement of ≥40% and ≥2 units in ≥3 ASAS domains, with no deterioration in the potential remaining domain; ITT = intent-to-treat; IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; 80S = 80 mg starting dose; 160S = 160 mg starting dose; NRI = nonresponder imputation.

Table 2. ASAS20 and ASAS40 Response Rates at Weeks 1 and 2 of COAST-X by Ixekizumab Starting Dose, NRI, ITT Population Prior to any Switch to Open-label to IXE Q2W 3

Response Parameter

ASAS20

ASAS20

ASAS20

ASAS20

ASAS40

ASAS40

ASAS40

ASAS40

Dosing Regimen

IXE Q4W

IXE Q4W

IXE Q2W

IXE Q2W

IXE Q4W

IXE Q4W

IXE Q2W

IXE Q2W

Starting Dose

80 mg 
n=47

160 mg
n=49

80 mg 
n=50

160 mg 
n=52

80 mg 
n=47

160 mg
n=49

80 mg
n=50

160 mg
n=52

Week 1, n (%)

14 (29.8)

13 (26.5)

11 (22.0)

17 (32.7)

7 (14.9)

6 (12.2)

3 (6.0)

9 (17.3)

Week 2, n (%)

17 (36.2)

14 (28.6)

15 (30.0)

22 (42.3)

12 (25.5)

6 (12.2)

8 (16.0)

9 (17.3)

Abbreviations: 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; ITT = intent-to-treat; 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.

Starting Dose in Plaque Psoriasis Trials

No ixekizumab clinical trials in patients with moderate-to-severe plaque psoriasis have directly compared administration with and without a 160 mg starting dose with regards to pharmacokinetics, efficacy, or safety.

Steady state concentrations were achieved by week 8 following the 160 mg starting dose and 80 mg Q2W dosing regimen for plaque psoriasis.3,5 In the phase 3 clinical trial UNCOVER-1, the 160 mg starting dose resulted in achievement of near steady state concentrations (greater than 80% of steady state after the first dose), and thus enabled a fast onset of response in this trial.3

Starting Dose in Psoriatic Arthritis Clinical Trials

No clinical trials of ixekizumab in patients with active psoriatic arthritis have directly compared administration with and without a 160 mg starting dose with regards to the pharmacokinetics, efficacy, or safety of ixekizumab. 

A starting dose of 160 mg ixekizumab was used to achieve steady state concentrations earlier and allow a rapid onset of responses.3

Approved Dosing Regimens

The approved dosing regimens for ixekizumab for the treatment of plaque psoriasis, active psoriatic arthritis, AS/r-axSpA, and nr-axSpA are shown below.

Plaque psoriasis in adults

The recommended dose is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg (one injection) at Weeks 2, 4, 6, 8, 10, and 12, then maintenance dosing of 80 mg (one injection) every 4 weeks.5

Psoriatic arthritis

The recommended dose is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg (one injection) every 4 weeks thereafter.5

For psoriatic arthritis patients with concomitant moderate to severe plaque psoriasis, the recommended dosing regimen is the same as for plaque psoriasis.5

Axial spondyloarthritis (radiographic and non-radiographic)

The recommended dose is 160 mg (two 80 mg injections) by subcutaneous injection at Week 0, followed by 80 mg every 4 weeks.5

References

1. 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

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

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

Glossary

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

nr-axSpA = nonradiographic axial spondyloarthritis

NSAID = nonsteroidal anti-inflammatory drug

Q2W = every 2 weeks

Q4W = every 4 weeks

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 15, 2020


Contact Lilly

Call or Email us

If you want to ask a Medical Information question or you want to report an adverse event or product complaint you can call us or email us at ukmedinfo@lilly.com

Available Mon - Fri, 8am - 4pm, excluding Bank Holidays

Or you can

Chat with Us If you have a question, you can chat online with a Lilly Medical Information professional.

Submit a question