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Taltz ® (ixekizumab)
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Taltz® (ixekizumab): How many patients developed uveitis with and without a prior history?
Treatment-emergent anterior uveitis has been reported in psoriasis, psoriatic arthritis, and axSpA clinical trials. This response provides patient-reported history of uveitis where available.
UK_cFAQ_IXE416_Z1_UVEITIS_PREEXISTING_TEAES_PsO_PsA_axSpA
en-GB
Background Information
This response includes reports of anterior uveitis (MedDRA-preferred term "iridocyclitis") in psoriasis, psoriatic arthritis, and axSpA (including AS/r-axSpA and nr-axSpA) clinical trials.
The most common extra-muscular-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 HLA-B27 status and duration of the spondyloarthropathy.1
Uveitis as Adverse Drug Reaction
Uveitis is not listed as adverse drug reaction in the Taltz summary of product characteristics.2
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. 3
Two (0.0%) TEAEs of anterior uveitis (MedDRA-preferred term "iridocyclitis") were reported of 6645 patients (accounting for 17,902.0 PY of exposure) exposed to ixekizumab across adult and pediatric plaque psoriasis clinical trials (including phase 1, phase 2, and phase 3) as of March 19, 2020.3
Preexisting and Treatment-Emergent Adverse Events of Anterior Uveitis in Psoriatic Arthritis Trials
Anterior uveitis (MedDRA-preferred term "iridocyclitis") was reported as a historical illness in 1 patient and as a preexisting condition in no patients randomized to ixekizumab 80 mg Q4W (N=454) in SPIRIT-P1 and SPIRIT-P2. Anterior uveitis was not reported as a preexisting condition and was reported as a historical illness in 1 patient in the phase 3 long-term efficacy trial SPIRIT-P3.3
No TEAEs of anterior uveitis (MedDRA-preferred term "iridocyclitis") were reported of 1401 patients (accounting for 2247.7 PYs of exposure) exposed to ixekizumab across PsA clinical trials as of March 19, 2020.3
New Onset and Flares of Anterior Uveitis in Ankylosing Spondylitis/Radiographic Axial Spondyloarthritis Trials
See Treatment-Emergent Anterior Uveitis in COAST-V and COAST-W Trials During 16-Week Double-Blind Treatment Period (Integrated) for information on new onset and flares of anterior uveitis during the 16-week blinded dosing period of COAST-V and COAST-W. A brief description of clinical trials referenced in this response is available in Appendix: Brief Clinical Trial Descriptions.
PBO |
IXE Q4W |
IXE Q2W |
|
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 Q4W treatment arm with a history of anterior uveitis, 2 patients experienced TE-anterior uveitis.3
Similarly, of the 47 patients in the ixekizumab 80 mg Q2W treatment arm with a history of anterior uveitis, 2 patients experienced TE-anterior uveitis.3
In each of the ixekizumab 80 mg treatment arms, there was 1 patient with no prior history of anterior uveitis that experienced TE-anterior uveitis.3
Reports of Anterior Uveitis Through 52 Weeks in Ankylosing Spondylitis/Radiographic Axial Spondyloarthritis Trials
Across both studies, 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)).7
One case resulted in ixekizumab treatment interruption, and 1 case resulted in permanent discontinuation of ixekizumab treatment. The EAIR for acute anterior uveitis through 52 weeks was 3.9 per 100 PY.7
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). Active anterior uveitis cases were evaluated by ophthalmologists.
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. A brief description of the clinical trial referenced in this response is available in Appendix: Brief Clinical Trial Descriptions.
|
PBO |
IXE Q4W |
IXE Q2W |
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.3
Of the 8 patients in the ixekizumab 80 mg Q2W treatment arm with a history of anterior uveitis, 2 patients experienced TE-anterior uveitis.3
In each of the ixekizumab 80 mg treatment arms, all patients with TE-anterior uveitis had a history of anterior uveitis.3
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; 1792.2 PY), as of March 19, 2020, anterior uveitis (MedDRA-preferred term "iridocyclitis") was reported as a TEAE in 50 patients (IR 2.8 per 100 PY). Among the 50 patients with iridocyclitis, 37 (74%) had a history of iridocyclitis and 2 (4%) patients discontinued due to iridocyclitis.9
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.10
Psoriatic Arthritis Trials
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.4,5
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
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
3Data on file, Eli Lilly and Company and/or one of its subsidiaries.
4Deodhar 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
5van 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
6Marzo-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.
7Schwartzman 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.
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
9Schwartzman S, Sandoval D, Kronbergs A, et al. Long-term safety profile of ixekizumab treatment on patients with axial spondyloarthritis. Abstract presented at: American College of Rheumatology/ARP 2020 Annual Scientific Meeting (Virtual); November 5-9, 2020.
10Gordon 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
11Nash 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
12Mease PJ, van der Heijde D, Ritchlin CT, et al; SPIRIT-P1 Study Group. 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
13A long-term efficacy and safety study of ixekizumab (LY2439821) in participants with active psoriatic arthritis (SPIRIT P3). ClinicalTrials.gov identifier: NCT02584855. Updated November 15, 2019. Accessed May 25, 2021. https://www.clinicaltrials.gov/ct2/show/NCT02584855
14A long term extension study of ixekizumab (LY2439821) in participants with axial spondyloarthritis. ClinicalTrials.gov identifier: NCT03129100. Updated June 18, 2021. Accessed July 13, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03129100
Glossary
AS/r-axSpA = ankylosing spondylitis/radiographic axial spondyloarthritis
axSpA = axial spondyloarthritis
bDMARD = biologic disease-modifying antirheumatic drug
EAIR = exposure adjusted incidence rate
IR = 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
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).10
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 Induction (UNCOVER-1, -2, -3) and Maintenance (UNCOVER-1, -2) Dosing Period Study Designs 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.2
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.12
- 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.11
- 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.13
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.5
- 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.4
- 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.8
- 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.14
Date of Last Review: 20 October 2020
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