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).

Taltz® (ixekizumab): What is the Long-Term Safety in Plaque Psoriasis?

Exposure-adjusted IR for TEAEs and SAEs remained stable or decreased over time in ixekizumab clinical trials.

UK_cFAQ_IXE334_LONG_TERM_SAFETY_PsO
UK_cFAQ_IXE334_LONG_TERM_SAFETY_PsO
en-GB

General Information

  • The long-term safety of ixekizumab has been evaluated in 6892 patients with psoriasis who received ixekizumab up to 5 years (a total of 18,025.7 patient years (PY) of ixekizumab exposure). The safety profile is consistent with previous reports in patients who received ixekizumab for the treatment of psoriasis and the rates of reported adverse events (AEs) did not increase with long-term exposure to ixekizumab.1
  • Comparisons between treatment periods described for the phase 3 UNCOVER trials summarized in this response are descriptive in nature, and not statistical comparisons.
  • Note that data from multiple, different dosing regimens, including unapproved doses, are included in this response.

Phase 3 Clinical Trials in Psoriasis

In an integrated analysis of safety data from 3 pivotal phase 3 clinical trials which had an induction period of 12 weeks, 2 of which were followed by a randomized withdrawal maintenance period of 48 additional weeks, the exposure adjusted incidence rate (EAIR) per 100 PYs for treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) remained stable or decreased over time through week 60 (Incidence Rates of Treatment-Emergent Adverse Events and Serious Adverse Events Through Week 60 in Phase 3 UNCOVER Clinical Trials).1,2

Across the 12-week induction periods of UNCOVER-1, -2, and -3, the 48-week maintenance periods of UNCOVER-1 and -2, and the long-term extension period to week 60 of UNCOVER-3, most TEAEs were mild or moderate in severity and generally did not lead to treatment discontinuation.3-5 In all 3 trials, long-term safety was evaluated for up to a total of 5 years in patients who participate through the entire studies.4

Incidence Rates of Treatment-Emergent Adverse Events and Serious Adverse Events Through Week 60 in Phase 3 UNCOVER Clinical Trials2,6

Event

12-Week Induction Period From UNCOVER-1, UNCOVER-2, and UNCOVER-3

48-Week Maintenance Period From UNCOVER-1 and UNCOVER-2

Placebo
(N=791; 180 PY)

IXE every 2 wks
(N=1167; 269 PY)

IXE every 4 wks
(N=1161; 266 PY)

Placebo
(N=402; 188 PY)

IXE every 4 wks
(N=416; 345 PY)

IXE every 12 wks
(N=408; 282 PY)

Any TEAE, IRa

205.5

253.6b

256.8b

123.8

95.6b

106.2

Any SAE, IRa

6.7

7.4

9.8

8.0

7.5

8.1

Abbreviations: IR = incidence rate; IXE = ixekizumab; PY = patient-years; SAE = serious adverse event; TEAE =-treatment-emergent adverse event.

aIncidence rates were calculated by dividing the total number of patients experiencing the TEAE by the sum of all patients’ time (in 100 years) of exposure during the treatment period.

bp<.05 vs placebo.

UNCOVER-3 Open-Label Long-Term Extension Data 

Treatment-Emergent Adverse Events, Serious Adverse Events, Deaths, and Discontinuations in the Open-Label Long-Term Extension Period of UNCOVER-3 summarizes safety data on TEAEs, SAEs, deaths, and discontinuations due to AEs from the open-label long-term extension period of the 264-week UNCOVER-3 trial for the patients who received the approved ixekizumab dosing regimen and all patients who received ixekizumab.7

Treatment-Emergent Adverse Events, Serious Adverse Events, Deaths, and Discontinuations in the Open-Label Long-Term Extension Period of UNCOVER-37

Event

Approved IXE Dosing Regimena LTE Period
1493.8 PY
n (IR)b

All IXE Exposure Population
5179.6 PY
n (IR)b

Patients with ≥1 TEAE

323 (21.6)

1134 (21.9)

Patients with ≥1 SAE

55 (3.7)

253 (4.9)

Deaths

3 (0.2)

11 (0.2)

Discontinuation due to AE

33 (2.2)

131 (2.5)

Abbreviations: AE = adverse event; IR = incidence rate; IXE = ixekizumab; LTE = long-term extension; PY = patient-years; 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.

aThe approved ixekizumab dosing regimen for moderate-to-severe plaque psoriasis is ixekizumab 160 mg at week 0, followed by 80 mg every 2 weeks through week 12, and 80 mg every 4 weeks thereafter. In UNCOVER-3, patients were allowed to escalate to every 2 weeks dosing after week 60 and remained on every 2 weeks dosing until study completion or discontinuation. The patients that dose-escalated are included in this approved dosing regimen population.

bIR per 100 PY.

Integrated Analysis of Ixekizumab Exposures

In 17 ixekizumab clinical trials for psoriasis, 6892 patients received at least 1 dose of ixekizumab, representing 18,025.7 PY of exposure as of the data cutoff of March 2021.1

Treatment-Emergent Adverse Events and Serious Adverse Events in All Treatment Periods in All Psoriasis Ixekizumab Exposures Integrated Analysis Set provides the numbers of TEAEs, SAEs, deaths, and discontinuations due to an AE as of March 2021 in the all psoriasis integrated exposures dataset.

Treatment-Emergent Adverse Events and Serious Adverse Events in All Treatment Periods in All Psoriasis Ixekizumab Exposures Integrated Analysis Set1

Event, n [IR]a

Pooled IXE
N=6892
18,025.7 PYb

Patients with ≥1 TEAE

5857 [32.5]c

Patients with ≥1 SAE

969 [5.4]

Deaths

36 [0.2]

Discontinuation due to AE

519 [2.9]

Abbreviations: AE = adverse event; IR = incidence rate; IXE = ixekizumab; PY = patient-years; 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 PY.

bData through March 2021.

cThe most commonly reported TEAEs (IR per 100 PYs) were nasopharyngitis (8.8) and upper respiratory tract infection (6.2).

Adverse Events of Special Interest in All Treatment Periods in All Psoriasis Ixekizumab Exposures Integrated Analysis Set1

Event, n [IR]a

Pooled IXE
N=6892
18,025.7 PYb

Infections

4307 [23.9]

Serious infections

231 [1.3]

Candida infections

337 [1.9]

Opportunistic infections

318 [1.8]

Injection site reactionsc

1056 [5.9]

Allergic/hypersensitivity reactions

1002 [5.6]

Cytopeniasd

171 [0.9]

Malignancies

141 [0.8]

MACEe

91 [0.5]

Depressionf

215 [1.2]

Inflammatory bowel diseaseg

26 [0.1]

Ulcerative colitis

16 [0.1]

Crohn's disease

10 [0.1]

Abbreviations: EPIMAD = Registre Epidemiologique des Maladies de l'Appareil Digestif; IR = incidence rate; IXE = ixekizumab; MACE = major adverse cerebro-cardiovascular events; MEdDRA = Medical Dictionary for Regulatory Activities; PY = patient-years; SMQ = standardized MedDRA query; TEAE = treatment-emergent adverse event.

aIR per 100 PY.

bData through March 2021.

cHigh level term.

dBroad, according to SMQ classification.

eConfirmed events.

fBroad, according to SMQ or sub-SMQ classification.

gThe data represent cases classified as ‘‘definite’’ and ‘‘probable’’ per external adjudication. IR was calculated as the total of ‘‘definite’’ and ‘‘probable’’ cases/total patient-years, then multiplied by 100. There were five cases of adjudicated IBD that were not considered TEAEs. Total adjudicated IBD n = 31 (IR of 0.2 per 100 PY, 0.4%).

Incidence Rates of Select Categories of Adverse Events at 1-Year Intervals, All Psoriasis Program Patients Exposed to Ixekizumab With Up To 5 Years of Treatment1,8

Figure 1 description: Incidence rates did not increase over 5 years for all treatment-emergent adverse events, serious adverse events, serious infections, injection-site reactions, infections, depression, major adverse cerebro-cardiovascular events, malignancies, and inflammatory bowel disease.

Abbreviations: IBD = inflammatory bowel disease; IR = incidence rate; IXE = ixekizumab; MACE = major adverse cerebro-cardiovascular events; PY = patient-years; SAE = serious adverse event; TEAE = treatment-emergent adverse event.

Notes: Inflammatory bowel disease IR summarized here represent confirmed cases per external adjudication. MACE were adjudicated events.

Please find the full list of adverse drug reactions of ixekizumab in the Taltz summary of product characteristics.9

References

1Griffiths CEM, Gooderham M, Colombel JF, et al. Safety of ixekizumab in adult patients with moderate-to-severe psoriasis: data from 17 clinical trials with over 18,000 patient-years of exposure. Dermatol Ther (Heidelb). 2022;12:1431-1446. https://doi.org/10.1007/s13555-022-00743-9

2Strober B, Papp KA, Leonardi C, et al. Integrated safety of ixekizumab in patients with moderate-to-severe psoriasis: results from a pooled analysis of 7 clinical trials. Poster presented at: 74th Annual Meeting of the American Academy of Dermatology; March 4-8, 2016; Washington, DC.

3Blauvelt A, Papp KA, Langley R, et al. Efficacy and safety of continuous ixekizumab treatment for 60 weeks in moderate-to-severe plaque psoriasis: Results from the UNCOVER-3 trial. Poster presented at: 74th Annual Meeting of the American Academy of Dermatology, March 4-8, 2016; Washington, DC

4Gordon 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

5Griffiths CEM, Reich K, Lebwohl M, et al; UNCOVER-2, UNCOVER-3 Investigators. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386(9993):541-551. https://doi.org/10.1016/S0140-6736(15)60125-8

6Strober B, Leonardi C, Papp KA, et al. Short- and long-term safety outcomes with ixekizumab from 7 clinical trials in psoriasis: etanercept comparisons and integrated data. J Am Acad Dermatol. 2017;76(3):432-440.e17. http://www.sciencedirect.com/science/article/pii/S0190962216308684

7Blauvelt A, Lebwohl MG, Mabuchi T, et al. Long-term efficacy and safety of ixekizumab: a 5-year analysis of the UNCOVER-3 randomized controlled trial. J Am Acad Dermatol. 2020;85(2):360-368. https://doi.org/10.1016/j.jaad.2020.11.022

8Griffiths CEM, Reich K, Gooderham M, et al. Long-term safety of ixekizumab in patients with moderate-to-severe psoriasis up to 5 years: pooled data from 16 clinical trials. Poster presented at: 29th Annual Meeting of the European Academy of Dermatology and Venereology (EADVirtual); October 29-31, 2020.

9Taltz [summary of product characteristics]. Eli Lilly and Company (Ireland) Limited, Ireland

Appendix: Clinical Trial Brief Descriptions 

Study Design of Induction (UNCOVER-1, -2, and -3) and Maintenance (UNCOVER-1 and -2) Dosing Periods4

Figure 2 description: The study design for UNCOVER-1, -2, and -3 12-week induction period and maintenance dosing periods for UNCOVER 1 and 2 are presented. Etanercept arm was not included in UNCOVER-1. Responders (static Physician Global Assessment 0 or 1) to ixekizumab at week 12 were rerandomized to receive ixekizumab every 4 weeks, ixekizumab every 12 weeks, or placebo. In UNCOVER-2 study, nonresponders to etanercept at week 12 were switched to ixekizumab every 4 weeks (without a 160-mg starting dose) after a 4‑week washout period. Nonresponders to placebo at week 12 received a 160-mg starting dose of ixekizumab followed by ixekizumab every 4 weeks. UNCOVER-3 study is not represented in maintenance period design as the extension period consisted of open-label treatment with ixekizumab every 4 weeks. 

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.

Note: ⁞ (dotted line) indicates relapse (sPGA ≥3).

Date of Last Review: 14 June 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