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): Iritis Preexisting Conditions and TEAEs in Clinical Trials

This response includes reports of iritis in psoriasis, psoriatic arthritis and axial spondyloarthritis clinical trials.

Iritis as Adverse Drug Reaction

Iritis is not listed as adverse drug reaction in the Taltz summary of product characteristics.1

Exclusion Criteria in Ixekizumab Clinical Trials

Ankylosing Spondylitis/Radiographic Axial Spondyloarthritis Trials

Patients with iritis were not explicitly excluded in the COAST-V and COAST-W studies. 2,3

Non-radiographic Axial Spondyloarthritis

Patients with iritis were not specifically excluded in the COAST-X study.4

Psoriatic Arthritis Trials

No specific exclusion criteria for iritis was included in the phase 3 psoriatic arthritis clinical trials. 5,6

Plaque Psoriasis Trials

No specific exclusion criteria for uveitis or iritis were included in the pivotal phase 3 plaque psoriasis clinical trials.7

Pre-existing and TEAEs of Iritis in Ixekizumab Clinical Trials

Treatment-emergent adverse events are defined as events that first occurred or worsened in severity, relative to baseline, at any time during a clinical study. The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a TEAE of the type listed. Adverse events reported during the studies were not necessarily caused by the therapy and the frequencies do not reflect investigator assessment of causality.

This information is for reference only and is not a treatment recommendation. Decisions regarding the use of ixekizumab in patients with iritis (or any medical condition) should be made at the discretion of the prescribing physician using their best clinical judgment.

Ankylosing Spondylitis/Radiographic Axial Spondyloarthritis Trials

Iritis was reported as a historical illness in 7 (1.9%) patients randomized to ixekizumab through week 16 in COAST-V and COAST-W.6

Non-radiographic Axial Spondyloarthritis Trial

Iritis was reported as a preexisting condition in 1 (0.5%)  patient randomized to ixekizumab in COAST-X.6

Incidence of Iritis in All Axial Spondyloarthritis Trials

The incidence rate of iritis across all patients exposed to ixekuzmab in axSpA trials (N=929; 1336.2 PYs) as of April 2019 is 0.4 per 100 PYs.6

Psoriatic Arthritis Trials

Iritis was not reported as preexisting or historical illness in any patient randomized to ixekizumab through week 24 in SPIRIT-P1, SPIRIT-P2, or SPIRIT-P3.6

One (0.1%) TEAE of iritis was reported out of 1401 patients exposed to ixekizumab across psoriatic arthritis clinical trials as of March 21, 2019.6

Plaque Psoriasis Trials

Iritis was not reported as a historical illness or preexisting condition in any patient randomized to ixekizumab through week 12 (N=2328) in UNCOVER -1, -2, and -3.6

Three (0.0%) TEAEs of iritis were reported out of 6091 patients exposed to ixekizumab across plaque psoriasis trials (including phase 1, phase 2, and phase 3) as of March 21, 2019.6

References

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

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. 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

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. Nash P, Kirkham B, Okada M, et al. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomized, 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

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

7. Gordon KB, Blauvelt A, Papp KA, et al. 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

8. Mease PJ, van der Heijde D, Ritchlin CT, et al. 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

9. A long-term efficacy and safety study of ixekizumab (LY2439821) in participants with active psoriatic arthritis (SPIRIT P3). ClinicalTrials.gov identifier: NCT02584855. Updated November 6, 2018. Accessed March 13, 2019. https://www.clinicaltrials.gov/ct2/show/NCT02584855?term=SPIRIT-P3&rank=1.

10. 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

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

bDMARD = biologic disease-modifying antirheumatic drug

EAIR = exposure adjusted incidence rate

MedDRA = Medical Dictionary for Regulatory Activities

nr-axSpA = nonradiographic axial spondyloarthritis

PsA = psoriatic arthritis

PY = patient-years

Q2W = every 2 weeks

Q4W = every 4 weeks

TEAE = treatment-emergent adverse event

TE = treatment-emergent

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.

Appendix: Brief Clinical Trial Descriptions

Plaque Psoriasis Trials

  • UNCOVER-1, -2, and -3 (N=3866) phase 3 trials in moderate-to-severe plaque psoriasis were integrated to evaluate the safety of ixekizumab in comparison to placebo up to 12 weeks after treatment initiation.

  • The phase 3 trials examined the efficacy and safety of ixekizumab compared with placebo and etanercept (UNCOVER-2 and -3) during induction treatment and vs placebo in maintenance (UNCOVER-1 and -2).7

Figure 1. Induction (UNCOVER-1, -2, -3) and Maintenance (UNCOVER-1, -2) Dosing Period Study Designs7

Abbreviations: ETN = etanercept; IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; IXE Q12W = ixekizumab 80 mg every 12 weeks; PBO = placebo; R = randomization; sPGA = static Physician Global Assessment.

Notes:
ETN arm was not included in UNCOVER-1.

Responders (sPGA 0 or 1) to ixekizumab at week 12 were re-randomized to receive IXE Q4W, IXE Q12W, or PBO.

Nonresponders to ETN at week 12 in UNCOVER-2 were switched to IXE Q4W (without a 160 mg starting dose) after a 4-week washout period.

Nonresponders to PBO at week 12 received a 160 mg starting dose of ixekizumab followed by IXE Q4W.

(dotted line) = relapse (sPGA≥3).

UNCOVER-3 is not represented in maintenance period design as the extension period consisted of open-label treatment with IXE Q4W.

Some dosing schedules shown in Figure 1 are not consistent with the approved dosing schedule for plaque psoriasis in the Taltz summary of product characteristics. Please refer to the Taltz summary of product characteristics for approved dosing.1

Psoriatic Arthritis Trials

  • SPIRIT-P1 (N=417) is a phase 3, 24-week double-blind, placebo-controlled trial with an active reference arm in patients with active PsA who are naïve to bDMARDs with an extension period of up to 3 years.8

  • SPIRIT-P2 (N=363) is a phase 3, 24-week double-blind, placebo-controlled trial in patients with active PsA and an inadequate response or intolerance to TNF inhibitor, with an extension period of up to 3 years.5

  • SPIRIT-P3 (N=570) consists of a 36-week open-label period followed by a randomized double-blind withdrawal period from week 36 to week 104. This trial is being conducted in patients naïve to bDMARDs.9

Axial Spondyloarthritis Trials

  • 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.3

  • 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.2

  • 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.10

Date of Last Review: October 04, 2019

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