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).

Is Injection Site Pain Common When Injecting Taltz® (ixekizumab)?

Pain is one of the most frequent injection site reactions.

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What is the Cause?

The specific cause(s) of injection site pain with ixekizumab is unknown.1 An association between the presence of anti-drug antibodies and safety, including injection site reactions (ISR), is unclear.1,2

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

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?

1.7% of patients (of total n=6892) spontaneously reported injection site pain as a separate event of all patients treated with ixekizumab across 17 psoriasis clinical trials (data cutoff March 2021).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

  • 28 patients (2.4%) in the ixekizumab Q2W dosing group 
  • 17 patients (1.5%) in the ixekizumab Q4W dosing group, and 
    • resulting in discontinuation of study drug for 1 patient
  • 14 patients (1.8%) in the placebo group.1,5

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 Every 2 Weeks During UNCOVER-1, -2, and -3 Psoriasis Clinical Trials (N=197) shows maximal pain of the ISRs reported using a follow-up questionnaire. 

Maximal Pain of ISRs in Patients Treated With Ixekizumab Every 2 Weeks During UNCOVER-1, -2, and -3 Psoriasis Clinical Trials (N=197)1

Figure 1 description. Of the patients with psoriasis treated with ixekizumab every 2 weeks, 49% experienced no injection site pain, 32% experienced mild injection site pain, 16% experienced moderate injection site pain, and 3% experienced severe injection site pain during the first 12 weeks.

Abbreviation: ISRs = Injection site reactions.
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 Every 4 Weeks 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

Maximal Pain of ISRs in Patients Treated With Ixekizumab Every 4 Weeks During SPIRIT-P1 and SPIRIT-P2 Psoriatic Arthritis Clinical Trials (N=40)5

Figure 2 description. Of the patients with psoriatic arthritis treated with ixekizumab every 4 weeks, 68% experienced no injection site pain, 25% experienced mild injection site pain, 5% experienced moderate injection site pain, and 2.5% experienced severe injection site pain during the first 24 weeks.

Abbreviation: ISRs = injection site reactions.
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 2096.2 PYs of ixekizumab exposure) as of March 2021.5  

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 Every 4 Weeks 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
Maximal Pain of ISRs in Patients Treated With Ixekizumab Every 4 Weeks During COAST-V and COAST-W AS/r-axSpA Clinical Trials (N=12)5

Figure 3 description. About 33% of patients with radiographic axial spondyloarthritis experienced no injection site pain, mild injection site pain, and moderate injection site pain, respectively. No patients experienced severe injection site pain during the first 16 weeks. 

Abbreviations: AS/r-axSpA = ankylosing spondylitis/radiographic axial spondyloarthritis; ISRs = Injection site reactions.
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

Date of Last Review: 11 February 2022


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