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)

Taltz® ▼ (ixekizumab): Anti-drug Antibodies/Immunogenicity

Anti-drug antibodies have occurred with ixekizumab. The majority were low-to-moderate titer.

Summary

  • Anti-drug antibodies (ADA) have occurred with ixekizumab. The majority were low-to-moderate titer.1,2 Comparisons of ADA incidence between products may be misleading due to the immunogenicity assay capabilities.3

  • Less than 2% of psoriasis patients had ADAs impacting efficacy during the first 12 weeks (induction phase). There were no effects on efficacy in subjects with ADAs as measured by the percentage of sPGA (0,1) responders re-randomized at week 12 through 60 weeks.4

  • Presence of ADA had no effect on efficacy in patients in the PsA trials.3

  • No association between ADAs and TEAEs, including allergic reactions, hypersensitivity events, and injection site reactions has been established.4,5

  • Incidences of ADAs described from product labeling and clinical trials may vary due to differences in the specific populations, dosing groups analyzed, and the cut-off dates for the analyses performed.

Plaque Psoriasis Population

Approximately 9–17% of plaque psoriasis patients treated with ixekizumab at the recommended dosing regimen developed anti-drug antibodies, the majority of which were low titres and not associated with reduced clinical response up to 60 weeks of treatment. However, approximately 1% of patients treated with ixekizumab had confirmed neutralising antibodies associated with low drug concentrations and reduced clinical response.5

  • The clinical effects of ixekizumab ADA are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.

    • Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.6

Plaque Psoriasis Clinical Trial Anti-Drug Antibody Results

  • The presence of ADA was investigated in ADA-evaluable patients in 3 randomized, controlled UNCOVER clinical trials during the induction periods (0-12 weeks) and the maintenance periods (12-60 weeks) of 2 of those trials.1

    • At 12 weeks, 91.0% of patients treated with the recommended dosing regimen did not develop ADAs.

    • At 60 weeks, 84.8% of patients treated with the recommended dosing regimen did not develop ADAs.1

    • For those patients who developed ADAs, 5.7% were low titer and not associated with reduced clinical response. Less than 2% of patients developed high titer ADAs (≥1:160) at week 12, and this was associated with lower response.1

    • At 12 weeks, 1% of patients were ADA-positive and developed antibodies characterized as NAb.3

Psoriatic Arthritis Population

In psoriatic arthritis patients treated with ixekizumab at the recommended dosing regimen up to 52 weeks, approximately 11% developed anti-drug antibodies, the majority of which were low titre, and approximately 8% had confirmed neutralising antibodies. No apparent association between the presence of neutralising antibodies and impact on drug concentration or efficacy was observed. 5

Psoriatic Arthritis Clinical Trial Anti-Drug Antibody Results

  • Anti-drug antibodies were also investigated in 2 pivotal placebo-controlled phase 3 studies in PsA.7

  • Fourteen patients (6.2%) treated with the recommended dosing regimen developed ADAs at week 24, the majority of which were classified as ADA low titer (SPIRIT-P1 and SPIRIT-P2).3

    • Two of the 14 patients had confirmed NAb.2

  • Clinical response did not appear to be affected by treatment-emergent ADAs at week 24 with Q4W dosing.3

    • Twenty percent improvement from baseline in ACR Index response rate was 90% (9/10) for patients with low titer ADAs and 75% (3/4) for patients with moderate-titer ADAs.3

    • No patients experienced high-titer ADAs.3

    • For the 2 patients who were NAb positive, ACR20 response rate at week 24 was 100% (Figure 1).3

Figure 1 contains information on dosing schedules that are not consistent with the information contained within the Summary of Product Characteristics (SmPC). Please refer to the SmPC for full prescribing information.5

Figure 1. ACR20 Response Rate (NRI) Stratified by ADA Titer (LOCF) Through Week 24 for SPIRIT-P1 and SPIRIT-P2 (Integrated)3

Abbreviations: ACR20 = 20% improvement in American College of Rheumatology Index; ADA = treatment-emergent antidrug antibody; IXE Q4W = ixekizumab 80 mg every 4 weeks after a 160 mg starting dose; IXE Q2W = ixekizumab 80 mg every 2 weeks after a 160 mg starting dose; LOCF = last observation carried forward; NAb = neutralizing antibody; NRI = nonresponder imputation; PBO = placebo.

NOTE: ADA status was determined using the LOCF method.

  • An association between ADAs and TEAEs, including allergic reactions, hypersensitivity events, and injection site reactions have not been established.4,5

Therapeutic Indications

Ixekizumab is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.5

Ixekizumab, alone or in combination with methotrexate, is indicated for the treatment of active psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drug (DMARD) therapies.5

References

1. Gordon KB, Blauvelt A, Papp KA, et al. 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

2. Mease PJ, Burmester G, Moriarty SR, et al. Safety of ixekizumab during 24 weeks of treatment in subjects with active psoriatic arthritis: Integrated safety analysis of two randomized, placebo controlled, phase 3 clinical trials. Poster presented at: 2017 American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) Annual Meeting; November 3-8, 2017; San Diego, CA.

3. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

4. Blauvelt A, Langley RG, Leonardi C, et al. Ixekizumab, a novel anti-IL-17A antibody, exhibits low immunogenicity during long-term treatment in patients with psoriasis. Poster presented at: 74th Annual Meeting of the American Academy of Dermatology; March 4-8, 2016; Washington, DC.

5. Taltz [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

6. Muram TM, Sloan JH, Chain JS, et al. A highly sensitive and drug-tolerant anti-drug antibody screening assay for ixekizumab using affinity capture elution. J Invest Dermatol. 2016; 136(7):1513-1515. http://dx.doi.org/10.1016/j.jid.2016.01.040.

7. Mease PJ, van der Heijde D, Ritchlin CT, et al. 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

Glossary

ACR = American College of Rheumatology

ACR20 = 20% improvement from baseline in American College of Rheumatology Index

ADA = treatment-emergent anti-drug antibody

NAb = neutralizing antibody

PsA = psoriatic arthritis

Q2W = every 2 weeks

Q4W = every 4 weeks

sPGA = static Physician Global Assessment

TEAE = treatment-emergent adverse event

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Date of Last Review: July 22, 2019

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