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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)
Is Injection Site Pain Common When Injecting Taltz® (ixekizumab)?
Pain is one of the most frequent injection site reactions.
UK_cFAQ_IXE401_Y1_INJECTION_SITE_PAIN_PsO_PsA_axSpA
en-GB
What is the Cause?
Does the Patient Need to Discontinue Ixekizumab Because of Injection Site Pain?
The severity of injection site pain was predominantly mild to moderate and did not lead to discontinuation of ixekizumab.2 The prescribing physician decides how to manage injection site pain using his best clinical judgment.
What Can the Patient Do to Reduce Injection Site Pain?
- The patient may alternate injection sites and, if possible, should avoid areas of the skin that show psoriasis.3
- The patient can wait 30 minutes to let the pre-filled pen or syringe warm to room temperature before using it. It is NOT allowed to use any heat sources to warm the medicine, for example: a microwave, hot water, or direct sunlight.3
- The package leaflet and the user manual give further instructions for administration.
Is It Better to Use the Syringe or the Autoinjector?
The UNCOVER-A study evaluated the effect of drug delivery device, either by autoinjector or prefilled syringe, on the pharmacokinetics of ixekizumab.4
Injection site pain typically occurs during injection.1 Therefore injection site pain was reported related to ISRs (see Background Information), but injection site pain was also reported as a separate event.
During the treatment period, 10 (9.8%) patients in the prefilled syringe group and 16 patients (15.7%) in the autoinjector group reported ISR.5
The investigator reported ISRs as possibly related to the device for
- 1 in the prefilled syringe group and
- 10 in the autoinjector group device.5
Approximately
- 2% of patients in the autoinjector group and
- 2% of patients in the prefilled syringe group
reported injection site pain as a separate event in the UNCOVER-A study.5
Injection Site Pain in Psoriasis, Psoriatic Arthritis, Axial Spondyloarthritis Clinical Trials
Brief descriptions of the trial designs are available in Appendix: Clinical Trial Descriptions.
Please note that multiple, different dosing regimens, including unapproved doses, are included in this response.
Psoriasis Clinical Trials
What Was the Incidence of Injection Site Pain For All Patients in the Psoriasis Clinical Trials?
1.9% of patients (n=6645) spontaneously reported injection site pain as a separate event of all patients treated with ixekizumab across 16 psoriasis clinical trials (data cutoff March 2020).5
Detailed Data From Pivotal Psoriasis Clinical Trials
Duri5ng the 12-week induction periods in 3 clinical trials, injection site pain was spontaneously reported in
Injection site pain was typically reported to occur during injection in the 12-week induction period.
16.9% of patients who received ixekizumab Q2W spontaneously reported an ISR (n=197/1167).1
- 51% of patients who reported an ISR experienced pain.
- Most patients (>90%) reported mild-to-moderate pain.1
Maximal Pain of ISRs in Patients Treated with Ixekizumab Q2W During UNCOVER-1, -2, and -3 Psoriasis Clinical Trials (N=197) shows maximal pain of the ISRs reported using a follow-up questionnaire.
Abbreviation: ISRs = Injection site reactions, Q2W = every 2 weeks
NOTE: Denominator for percentages in figure is 197, or the number of patients who reported an ISR of any type in UNCOVER-1, -2, and -3.
Psoriatic Arthritis Clinical Trials
What Was the Incidence of Injection Site Pain For All Patients in the Psoriatic Arthritis Clinical Trials?
1.6% of patients (n=22) spontaneously reported injection site pain as a separate event of all patients treated with ixekizumab across 4 psoriatic arthritis clinical trials as of March 2020 (N=1401 patients accounting for 2247.7 patient years (PY) of exposure to ixekizumab).5
Detailed Data From Pivotal Psoriatic Arthritis Clinical Trials
During the 24 weeks of the 2 clinical trials, injection site pain was spontaneously reported in
- 2 patients (0.9%) in the ixekizumab Q4W dosing group
- 2 patients (0.9%) in the ixekizumab Q2W dosing group, and
- 5 patients (2.2%) in the placebo group.5
Injection site pain resulted in discontinuation of study drug for
- 1 patient in the placebo group, and
- no patients in the ixekizumab treatment groups.5
Maximal Pain of ISRs in Patients Treated with Ixekizumab Q4W During SPIRIT-P1 and SPIRIT-P2 Psoriatic Arthritis Clinical Trials (N=40) shows solicited data from a follow-up questionnaire. 40 patients treated with ixekizumab reported an ISR during the placebo-controlled treatment period of 2 clinical trials.5
13 patients experienced pain, out of which 2 were moderate and 1 was severe.5
Abbreviation: ISRs = Injection site reactions; Q4W = every 4 weeks.
NOTE: Denominator for percentages in figure is 40, or the number of patients who reported an ISR of any type in SPIRIT-P1 and SPIRIT-P2.
axSpA Clinical Trials
What Was the Incidence of Injection Site Pain For All Patients in the axSpA Clinical Trials?
12 (1.3%) patients reported injection site pain as a separate event across 4 axSpA clinical trials (N=932 patients accounting for 1792.2 PYs of ixekizumab exposure) as of March 2020.5
Detailed Data From Pivotal AS/r-axSpA Trials
During the 16 weeks of COAST-V and COAST-W, injection site pain was spontaneously reported in
- 4 patients (2.1%) in the ixekizumab Q4W dosing group
- resulting in discontinuation of study drug for 1 patient
- 5 patients (2.8%) in the ixekizumab Q2W dosing group, and
- 4 patients (2.1%) in the placebo group.5
Maximal Pain of ISRs in Patients Treated with Ixekizumab Q4W During COAST-V and COAST-W AS/r-axSpA Clinical Trials (N=12) shows solicited data from a follow-up questionnaire. 12 patients treated with ixekizumab 80 mg Q4W reported an ISR during the placebo-controlled treatment period of COAST-V and COAST-W.5
- 8 patients experienced pain, out of which 4 were moderate and 4 were severe.5
Abbreviations: AS/r-axSpA = ankylosing spondylitis/radiographic axial spondyloarthritis; ISRs = Injection site reactions; Q4W = every 4 weeks.
NOTE: Denominator for percentages in figure is 12, or the number of patients who reported an ISR of any type in COAST-V and COAST-W.
Data From Nonradiographic Axial Spondyloarthritis Trial
During the 52 weeks of COAST-X, injection site pain was spontaneously reported in 1 patient each in both
- the ixekizumab treatment groups and
- in the placebo group (1.0% of patients in each group).5
Injection site pain resulted in discontinuation of study drug for
- 1 patient in the placebo group, and
- no patients in the ixekizumab treatment groups.5
This data includes cases of injection site pain reported prior to any switch to open-label ixekizumab Q2W, which was allowed at the investigator's discretion from week 16 of COAST-X.5,6
Background Information
Unsolicited adverse event (AE) data were reported in psoriasis, psoriatic arthritis, and axial spondyloarthritis clinical trials and were later coded using MedDRA (Medical Dictionary for Regulatory Activities) terms. We collected solicited AE data using a standardized questionnaire only if patients initially reported an ISR of any type.1
Some of the preferred terms that are included in the high-level group term of ISRs are
- injection site bruising
- injection site erythema
- injection site mass
- injection site pain
- injection site pruritus
- injection site rash
- injection site reaction
- injection site swelling
- injection site urticaria, and
- injection site warmth.5
Data in this response include
- unsolicited ISR TEAEs reported in clinical trials, and
- solicited data from follow-up questionnaire completed by patients reporting an ISR of any type (questionnaire used in phase 3 trials only).5
References
1Shear NH, Paul C, Blauvelt A, et al. Safety and tolerability of ixekizumab: integrated analysis of injection-site reactions from 11 clinical trials. J Drugs Dermatol. 2018;17(2):200-206. http://jddonline.com/articles/dermatology/S1545961618P0200X
2Taltz [summary of product characteristics]. Eli Lilly and Company (Ireland) Limited, Ireland
3Taltz 80 mg solution for injection in pre-filled pen [Instructions for use]. Eli Lilly and Company (Ireland) Limited, Ireland
4Duffin KC, Bagel J, Bukhalo M, et al. Phase 3, open-label, randomized study of the pharmacokinetics, efficacy and safety of ixekizumab following subcutaneous administration using a prefilled syringe or an autoinjector in patients with moderate-to-severe plaque psoriasis (UNCOVER-A). J Eur Acad Dermatol Venereol. 2017;31(1):107-113. https://doi.org/10.1111/jdv.13768
5Data on file, Eli Lilly and Company and/or one of its subsidiaries.
6Deodhar 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
7Gordon 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
8Mease 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
9Nash 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
10van 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
11Deodhar 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
12A 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
nr-axSpA = nonradiographic axial spondyloarthritis
PsA = psoriatic arthritis
Appendix: Clinical Trial Descriptions
Plaque Psoriasis
- UNCOVER-1, -2, and -3 (N=3866) phase 3 trials, conducted in patients with moderate-to-severe plaque psoriasis, were integrated to evaluate the safety of ixekizumab up to 12 weeks after treatment initiation in comparison to placebo. The phase 3 trials examined efficacy and safety of ixekizumab compared with placebo and etanercept (UNCOVER-2 and -3) during induction dosing period and vs placebo during maintenance period (UNCOVER-1 and -2).7
Psoriatic Arthritis
- SPIRIT-P1 (N=417) was a phase 3, 24-week double-blind, placebo-controlled trial with an active reference arm, conducted in patients with active PsA who were naïve to bDMARDs (biologic disease-modifying antirheumatic drug) with an extension period of up to 3 years.8
- SPIRIT-P2 (N=363) was a phase 3, 24-week double-blind, placebo-controlled trial, conducted in patients with active PsA and an inadequate response or intolerance to TNF (tumor necrosis factor) inhibitors, with an extension period of up to 3 years.9
Axial Spondyloarthritis
- COAST-V (N=341) was a phase 3, 16-week double-blind, placebo-controlled trial with an active reference arm and a dose double-blind extension period of 52 weeks, conducted in patients with active AS/r-axSpA who were naïve to bDMARDs.10
- COAST-W (N=316) was a phase 3, 16-week double-blind, placebo-controlled trial with a dose double-blind extension period of 52 weeks, conducted in patients with active AS/r-axSpA and an inadequate response or intolerance to 1 or 2 TNF inhibitors.11
- COAST-X (N=303) was a phase 3, 52-week double-blind, placebo-controlled trial, conducted in patients with nr-axSpA who were naïve to bDMARDs.6
- COAST-Y (N=773) is a phase 3, 104-week, long-term extension trial including a double-blind, placebo-controlled 40-week randomized withdrawal-retreatment period, is conducted in patients with axial spondyloarthritis who have completed the final study visit in COAST-V, COAST-W, or COAST-X.12
Date of Last Review: July 21, 2020
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