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Taltz ® (ixekizumab) injection
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TALTZ® (ixekizumab): Long-Term Safety for Psoriatic Arthritis
Exposure-adjusted IR for TEAEs and SAEs remained stable or decreased over time in ixekizumab clinical trials.
US_cFAQ_IXE334_LONG_TERM_SAFETY_PsA
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General Information
- Brief descriptions of the pivotal clinical trials for active PsA are provided at the end of this response (see Appendix: Clinical Trial Brief Descriptions).
- Note that data from multiple, different dosing regimens, including unapproved doses, are included in this response.
- The long-term safety of ixekizumab has been evaluated in 1401 patients with PsA who received ixekizumab up to 3 years (2228.6 PYs). The safety profile is consistent with previous reports in patients who received ixekizumab for the treatment of PsO or PsA and the rates of reported AEs remained stable or decreased over time with continued ixekizumab exposure.1
Phase 3 Clinical Trials
Incidence rates of TEAEs and SAEs from 3 phase 3 clinical trials with data through 96 weeks are illustrated in Incidence Rates of TEAEs and SAEs in the Double-blind Treatment Period and Integrated PsA Dataset. Among all ixekizumab exposures in PsA (data from SPIRIT-P1, -P2, and -P3; N=1118; PY=1373.4), the IR of overall TEAEs decreased with longer ixekizumab exposure. Some variation in SAE IRs were noted, but authors concluded that there was no clinically meaningful increase in the exposure-adjusted IR with longer ixekizumab exposures.2
As presented in Overview of Adverse Events, Integrated PsA Safety Dataset, most TEAEs were mild-to-moderate in severity and few led to discontinuation. The most common TEAEs were ISR, upper respiratory tract infections, and nasopharyngitis.2
There was no increase in IRs of AESIs analyzed over 12-week intervals through 96 weeks, including
- infection-related TEAEs
- ISR
- MACE
- hypersensitivity reactions
- malignancy, and
- depression-related events.2
One case each of UC and CD were reported. These were SAEs but did not lead to discontinuation of ixekizumab treatment. The CD event was reported as a new case, though the patient did have a history of irritable bowel syndrome. Of the 12 patients with preexisting conditions or a history of illness suggestive of IBD, none experienced disease exacerbation during ixekizumab treatment.2
Four deaths were reported. Causes of death were due to pneumonia, cerebrovascular accident, cardiorespiratory arrest, and drowning.2
Abbreviations: IR = incidence rate; IXE = ixekizumab; PBO = placebo; PsA = psoriatic arthritis; PY = patient-years; SAE = serious adverse event; TEAE = treatment-emergent adverse event.
aData are IR for 0-24 Weeks for the Double-blind Treatment Period (dotted line) for SPIRIT-P1 and -P2 only (inadequate responders excluded from week 16).
bData are mean IR by 12-week intervals to Week 96 for the Integrated PsA dataset (SPIRIT-P1, -P2, and -P3).
n (IR) [95% CI] |
All PsA IXE |
≥1 TEAE |
868 (63.2) [59.1, 67.5] |
|
392 (28.5) [25.9, 31.5] |
|
396 (28.8) [26.1, 31.8] |
|
80 (5.8) [4.7, 7.3] |
≥1 SAE |
91 (6.6) [5.4, 8.1] |
Deaths |
4 (0.3) [0.1, 0.8] |
Discontinuations due to adverse event |
80 (5.8) [4.7, 7.3] |
Abbreviations: IR = incidence rate; IXE = ixekizumab; PsA = psoriatic arthritis; PY = patient years; SAE = serious adverse event; TEAE = treatment-emergent adverse event.
NOTE: Patients with multiple occurrences of the same event are categorized by the highest severity.
Integrated Analysis of Ixekizumab Exposures
In 4 completed and ongoing ixekizumab clinical trials for PsA, 1401 patients with active PsA have received at least 1 dose of ixekizumab, representing 2228.6 PYs of exposure as of the data cutoff of March 21, 2019.1
The numbers of TEAEs, SAEs, deaths, and discontinuations due to an AE as of March 21, 2019 are shown in Treatment-Emergent Adverse Events and Serious Adverse Events in All Treatment Periods in All Psoriatic Arthritis Ixekizumab Exposures Integrated Analysis Set.
The rate of discontinuation from study drug due to an AE was similar between all PsA ixekizumab exposures (114/1401; 8.1%) and all PsO ixekizumab exposures (490/6091; 8.0%).1
The numbers of TEAEs of special interest as of March 21, 2019 are shown in Adverse Events of Special Interest in All Treatment Periods in All Psoriatic Arthritis Ixekizumab Exposures Integrated Analysis Set.
Event, n (%) [IR]a |
Pooled IXE |
Patients with ≥1 TEAE |
1128 (80.5) [50.6]c |
Patients with ≥1 SAE |
133 (9.5) [6.0] |
Deaths |
6 (0.4) [0.3] |
Discontinuation due to AE |
114 (8.1) [5.1] |
Abbreviations: AE = adverse event; IR = incidence rate; IXE = ixekizumab; PY = patient year; SAE = serious adverse event; TEAE = treatment-emergent adverse event.
Notes: Patients may be counted in more than one category. Patients with multiple occurrences of the same event are categorized by the highest severity. Deaths are included among SAEs and among discontinuations due to AEs.
aIR per 100 PYs.
bData through March 21, 2019.
cThe most commonly reported TEAEs (IR per 100 PYs) were nasopharyngitis (9.1), upper respiratory tract infection (unspecified: 8.3), and injection site reaction (7.0).
Event, n (%) [IR]a |
Pooled IXE |
Infections |
759 (54.2) [34.1] |
Serious infections |
28 (2.0) [1.3] |
Oral candidiasis |
16 (1.1) [0.7] |
Injection site reactions |
259 (18.5) [11.6] |
Inflammatory bowel disease (unadjudicated) |
4 (0.3) [0.2]c |
MACE (adjudicated) |
12 (0.9) [0.5] |
Malignancies |
15 (1.1) [0.7] |
Depression |
37 (2.6) [1.7]d |
Abbreviations: IR = incidence rate; IXE = ixekizumab; MACE = major adverse cerebro-cardiovascular events; PY = patient year.
aThe IR per 100 PYs considered exposure time as the entire time on ixekizumab.
bData through March 21, 2019.
cThe IR of adjudicated inflammatory bowel disease was 0.1.
dThe rate of suicide ideation or behavior was <.01. There were no completed suicides in the psoriatic arthritis clinical studies.
The rates of TEAEs including SAEs remained stable or decreased over time with continued exposure to ixekizumab up to 3 years (see Incidence Rates of Select Categories of Adverse Events at 1-year Intervals Up to 3 Years of Treatment in Patients Exposed to Ixekizumab in the Psoriatic Arthritis Clinical Development Program).1
Abbreviations: IBD = inflammatory bowel disease; IR = incidence rate; IXE = ixekizumab; MACE = major adverse cerebro-cardiovascular events; PBO = placebo; PsA = psoriatic arthritis; PY = patient years; SAE = serious adverse events.
a Data are IR for 0-24 weeks for the double-blind period for SPIRIT-P1 and -P2 only.
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Genovese MC, Kameda H, Rahman P, et al. Safety profile of ixekizumab in patients with moderate-to-severe plaque psoriasis and psoriatic arthritis: integrated analysis of 18 clinical trials. Poster presented at: American College of Rheumatology/ARP; November 8-13, 2019; Atlanta, GA.
2Mease P, Roussou E, Burmester GR, et al. Safety of ixekizumab in patients with psoriatic arthritis: results from a pooled analysis of three clinical trials. Arthritis Care Res (Hoboken). 2019;71(3):367-378. http://dx.doi.org/doi:10.1002/acr.23738
3Goupille P, Roussou E, Burmester G, et al. SAT0348 Safety of ixekizumab in patients with psoriatic arthritis: results from a pooled analysis of three clinical trials [abstract]. Ann Rheum Dis. 2018;77(suppl 2):1039-1040. http://dx.doi.org/10.1136/annrheumdis-2018-eular.2132
4Mease 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
5Nash 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
6A 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 September 25, 2020. https://www.clinicaltrials.gov/ct2/show/NCT02584855
Glossary
AE = adverse event
AESI = adverse event of special interest
bDMARD = biologic disease-modifying antirheumatic drug
CD = Crohn's disease
IBD = inflammatory bowel disease
IR = incidence rate
ISR = injection site reaction
MACE - major adverse cardiovascular events
PsA = psoriatic arthritis
PsO = psoriasis
PY = patient-years
SAE = serious adverse event
TEAE = treatment-emergent adverse event
TNF = tumor necrosis factor
UC = ulcerative colitis
Appendix: Clinical Trial Brief Descriptions
- 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.4
- 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.6
Date of Last Review: October 18, 2019
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