Taltz ® (ixekizumab)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information.For current prescribing information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk (England, Scotland, Wales) or www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).

What data are available on using Taltz® (ixekizumab) in patients with uveitis?

This response provides information on patients with uveitis as a pre-existing condition in ixekizumab trials. The decision to use ixekizumab in patients with uveitis is at the discretion of the prescribing physician.

UK_cFAQ_IXE416_Z1_UVEITIS_PREEXISTING_TEAES_PsO_PsA_axSpA
UK_cFAQ_IXE416_Z1_UVEITIS_PREEXISTING_TEAES_PsO_PsA_axSpA
en-GB

Background Information

This response includes reports of uveitis in psoriasis, psoriatic arthritis, and axial spondyloarthritis (axSpA) clinical trials. Axial spondyloarthritis includes ankylosing spondylitis (AS/r-axSpA) and nonradiographic axial spondyloarthritis (nr-axSpA).

The most common extramuscular skeletal feature of spondyloarthritis is uveitis. Up to 50% of patients with AS/r-axSpA will experience uveitis, and the most common type is anterior uveitis. The occurrence of uveitis has been associated with Human Leukocyte B-27 (HLA-B27) status and duration of the spondyloarthropathy.1

Treatment-emergent adverse events (TEAEs) 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 uveitis (or any medical condition) should be made at the discretion of the prescribing physician using their best clinical judgment.

Uveitis as Adverse Drug Reaction

Uveitis is not listed as adverse drug reaction in the Taltz summary of product characteristics. 2

Exclusion Criteria in Ixekizumab Clinical Trials Related to Uveitis

Plaque Psoriasis Trials

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

Psoriatic Arthritis Trials

Patients with active vasculitis or uveitis were excluded from participation in the phase 3 psoriatic arthritis clinical trials.4,5

Ankylosing Spondylitis/Radiographic Axial Spondyloarthritis Trials

Patients were excluded from COAST-V and COAST-W if they had evidence of active anterior uveitis (an acute episode) within the last 4 weeks prior to baseline randomization. These patients were allowed to be rescreened only 1 time ≥4 weeks after resolution of acute symptoms. Other patients with a previous history of uveitis were allowed to be enrolled in the study.6,7

Non-radiographic Axial Spondyloarthritis

Patients were excluded from COAST-X if they had evidence of active anterior uveitis (an acute episode) within the last 42 days prior to baseline randomization. These patients were allowed to be rescreened only 1 time ≥4 weeks after resolution of acute symptoms. Other patients with a previous history of uveitis were allowed to be enrolled in the study.8

History of Anterior Uveitis and Treatment-Emergent Adverse Events of Anterior Uveitis in Ixekizumab Clinical Trials

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.2

Preexisting and Treatment-Emergent Adverse Events of Anterior Uveitis in Plaque Psoriasis Trials

Anterior uveitis was reported as a historical illness in 1 patient and as a preexisting condition in no patients randomized to ixekizumab through week 12 (N=2328) in UNCOVER-1, -2, and -3 trials.5

Of 6892 patients (accounting for 18,025.7 PYs of exposure) exposed to ixekizumab across adult plaque psoriasis clinical trials as of March 2022, uveitis (MedDRA preferred term "uveitis") was reported in 4 patients (0.1%; IR=0.0 per 100 PYs).5,9

Preexisting and Treatment-Emergent Adverse Events of Anterior Uveitis in Psoriatic Arthritis Trials

Anterior uveitis was not reported as a preexisting condition and was reported as a historical illness in 1 patient in the SPIRIT-P1 and -P2 trials (N=454) and in 1 patient in the phase 3 long-term efficacy trial SPIRIT-P3 (N=394).5

No TEAEs of uveitis (MedDRA preferred term "uveitis") were reported out of 1401 patients (accounting for 2247.7 PYs of exposure) exposed to ixekizumab across psoriatic arthritis clinical trials as of March 2022.5,9

New Onset and Flares of Anterior Uveitis in Ankylosing Spondylitis/Radiographic Axial Spondyloarthritis Trials

Treatment-Emergent Anterior Uveitis in COAST-V and COAST-W Trials During 16-Week Double-Blind Treatment Period (Integrated) shows information on new onset and flares of anterior uveitis during the 16-week blinded dosing period of COAST-V and COAST-W trials.

Treatment-Emergent Anterior Uveitisa in COAST-V and COAST-W Trials During 16-Week Double-Blind Treatment Period (Integrated)5-7,10


PBO
(N=190)

IXE Q4W
(N=195)

IXE Q2W
(N=181)

Patients with a history of anterior uveitis, n

41

38

47

Total patients with ≥1 TE-anterior uveitis, n

0

3

3

Patients with ≥1 TE-anterior uveitis and a history of anterior uveitis

0

2

2

Patients with ≥1 TE-anterior uveitis and no history of anterior uveitis

0

1

1

Abbreviations: IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo; TE = treatment-emergent.

aAcute anterior uveitis was identified using the preferred term “iridocyclitis” (MedDRA Version 21.0).

Of the 38 patients in the ixekizumab 80 mg every 4 weeks (Q4W) treatment arm with a history of anterior uveitis, 2 patients experienced treatment-emergent (TE)-anterior uveitis.5

Similarly, of the 47 patients in the ixekizumab 80 mg every 2 weeks (Q2W) treatment arm with a history of anterior uveitis, 2 patients experienced TE-anterior uveitis.5

In each of the ixekizumab 80 mg treatment arms, there was 1 patient with no history of anterior uveitis that experienced TE-anterior uveitis.5

Reports of Anterior Uveitis Through 52 Weeks in Ankylosing Spondylitis/Radiographic Axial Spondyloarthritis Trials

Across both COAST-V and COAST-W trials, 22.1% of patients had a history of acute anterior uveitis, and 20 patients reported events of acute anterior uveitis. Of those patients who reported events of anterior uveitis during the trials, 15 had a history of the condition (Treatment-Emergent Anterior Uveitis in COAST-V and COAST-W Trials Through 52 Weeks of Treatment (Integrated)).11

One case resulted in ixekizumab treatment interruption, and 1 case resulted in permanent discontinuation of ixekizumab treatment. The exposure-adjusted incidence rate (EAIR) for acute anterior uveitis through 52 weeks was 3.9 per 100 patient-years (PYs).11

Treatment-Emergent Anterior Uveitisa in COAST-V and COAST-W Trials Through 52 Weeks of Treatment (Integrated)11


(N=641)

Patients with a history of anterior uveitis, n (%)

145 (22.1)

Patients with ≥1 TE-anterior uveitis, n (%)

20 (3.1)

Patients with ≥1 TE-anterior uveitis and a history of anterior uveitis

15

Patients with ≥1 TE-anterior uveitis and no history of anterior uveitis

5

Acute anterior uveitis EAIR per 100 PY

3.9

Abbreviations: EAIR = exposure-adjusted incidence rate; MedDRA = Medical Dictionary for Regulatory Activities; PY = patient-year; TE = treatment-emergent.

aAcute anterior uveitis was identified using the preferred term “iridocyclitis” (MedDRA Version 21.0). Ophthalmologists evaluated active anterior uveitis cases.

New Onset and Flares of Anterior Uveitis in Non-radiographic Axial Spondyloarthritis Trials

Treatment-Emergent Anterior Uveitis in COAST-X Trial During 52-Week Double-Blind Treatment Period shows information on new onset and flares of anterior uveitis during the double-blind treatment period of COAST-X.

Treatment-Emergent Anterior Uveitisa in COAST-X Trial During 52-Week Double-Blind Treatment Periodb5,8

 

PBO
(N=105)

IXE Q4W
(N=96)

IXE Q2W
(N=102)

Patients with a history of anterior uveitis, n

12

14

8

Total patients with ≥1 TE-uveitis, n

2

1

2

Patients with ≥1 TE-anterior uveitis and a history of anterior uveitis

2

1

2

Patients with ≥1 TE-anterior uveitis and no history of anterior uveitis

0

0

0

Abbreviations: IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo; TE = treatment-emergent.

aAcute anterior uveitis was identified using the preferred term “iridocyclitis” (MedDRA Version 21.0).

bPrior to biologic rescue with ixekizumab 80 mg Q2W.

Of the 14 patients in the ixekizumab 80 mg Q4W treatment arm with a history of anterior uveitis, 1 patient experienced TE-anterior uveitis.5

Of the 8 patients in the ixekizumab 80 mg Q2W treatment arm with a history of anterior uveitis, 2 patients experienced TE-anterior uveitis.5

In each of the ixekizumab 80 mg treatment arms, all patients with TE-anterior uveitis had a history of anterior uveitis.5

Incidence of Anterior Uveitis in All Axial Spondyloarthritis Trials

Among all ixekizumab exposures in 4 axSpA trials (including AS/r-axSpA and nr-axSpA) (N=932; 2097.7 PYs), as of March 2022, uveitis (Medical Dictionary for Regulatory Activities [MedDRA] preferred term "uveitis") was reported in 8 patients (0.9%; IR=0.4 per 100 PYs).5,9

As of March 2022, 58 patients had confirmed uveitis (MedDRA preferred term "iridocyclitis"), and 43 of those patients had a history of iridocyclitis.5,9

References

1Khan MA, Haroon M, Rosenbaum JT. Acute anterior uveitis and spondyloarthritis: more than meets the eye. Curr Rheumatol Rep. 2015;17(9):59. https://dx.doi.org/10.1007/s11926-015-0536-x

2Taltz [summary of product characteristics]. Eli Lilly and Company (Ireland) Limited, Ireland

3Gordon KB, Blauvelt A, Papp KA, et al; UNCOVER-1, UNCOVER-2, and UNCOVER-3 Study Groups. 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

4Nash P, Kirkham B, Okada M, et al; SPIRIT-P2 Study Group. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, 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

5Data on file, Eli Lilly and Company and/or one of its subsidiaries.

6Deodhar 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

7van 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

8Deodhar 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

9Deodhar A, Blauvelt A, Schwartzman S, et al. Long-term safety of ixekizumab in adult patients with psoriasis, psoriatic arthritis, and axial spondyloarthritis. Poster presented at: American College of Rheumatology/ARP - 2022 Annual Scientific Meeting; November 10-14, 2022; Philadelphia, Pennsylvania.

10Marzo-Ortega H, Mysler E, Tomita T, et al. Long-term safety of ixekizumab in patients with radiographic axial spondyloarthritis/ankylosing spondylitis: An integrated analysis of COAST-V and COAST-W. Poster presented at: European League Against Rheumatism; June 12-15, 2019; Madrid, Spain.

11Schwartzman S, Deodhar A, Kronbergs A, et al. Inflammatory bowel disease and anterior uveitis in patients treated with ixekizumab for radiographic axial spondyloarthritis: Results from two phase 3 studies through 52 weeks. Poster presented at: American College of Rheumatology/ARHP Annual Scientific Meeting; November 8-13, 2019; Atlanta, GA.

Date of Last Review: 27 October 2022


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, 10am - 4pm, excluding Bank Holidays

Or you can

Chat with Us

Click to Chat is Offline

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

Submit a request