Taltz ® (ixekizumab) injektion

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Taltz® (ixekizumab): Tidigare Biologisk Användning och effektivitet mot plackpsoriasis

Undersökning av tidigare behandling med ett biologiskt läkemedel identifierade inte skillnader i effekt av ixekizumab bland undergrupper vid vecka 12.

Short Summary

The efficacy and safety of ixekizumab was demonstrated regardless of previous treatment with a biologic. Ixekizumab was efficacious in systemic treatment-naive, biologic-naive, biologic/anti-TNF-exposed and biologic/anti-TNF-failure patients.1

An analysis of patients with prior use of non-biologic systemic therapies (including methotrexate, cyclosporine, retinoids, and psoralen/ultraviolet therapy) concluded that ixekizumab was effective irrespective of prior exposure to non-biologic systemic agents.2

Prior Biologic and Non-Biologic Systemic Therapy Use in the Pivotal Phase 3 Psoriasis Studies

Note that different dosing regimens, including unapproved doses, are included in this response. Please refer to the Taltz summary of product characteristics for approved dosing.1

Examination of the presence or absence of previous treatment with a biologic did not identify a difference in response at week 12 of the pivotal phase 3 UNCOVER clinical trials.3

Across 3 multicenter, randomized, double-blind, placebo-controlled trials (UNCOVER-1, -2, and -3), 26% of patients had received prior biologic therapy for the treatment of psoriasis.4 Of these,

  • 15% had received at least 1 anti-TNF alpha agent, and

  • 9% had received an anti-IL-12/IL-23.3

Previous biologics received in over 5% of patients in UNCOVER-1 were

  • etanercept (range 17%-20% across treatment arms)

  • adalimumab (12%-13%)

  • ustekinumab (12%-13%), and

  • infliximab (4%-8%).5

Previous biologics received in UNCOVER-2 and -3 included

  • adalimumab (range 5%-10% across treatment arms)

  • ustekinumab (5%-10%), and

  • infliximab (1%-5%).6

Patients were excluded from the 3 pivotal trials if they had previously received IL-17 antagonists. Patients with prior use of etanercept were excluded from UNCOVER-2 and -3.7

Patients were required to undergo a washout period with the range of 3 to 6 half-lives of any previous biologic agent prior to study baseline.7

Ixekizumab Efficacy Stratified by Previous Biologic Use

Patient reported reasons for stopping previous biologics prior to entering the UNCOVER trials were collected, but not systematically defined. Therefore, data on efficacy or safety of ixekizumab after patient exposure to a previous biologic therapy is not stratified by reason for stopping prior biologics.

UNCOVER-2 and -3 Pooled Secondary Analysis at Week 12

As shown in Figure 1, both doses of ixekizumab (80 mg Q2W and 80 mg Q4W) provided higher efficacy compared to etanercept regardless of previous biologic use.8,9

Figure 1. Pooled UNCOVER-2 and -3: PASI Response Rates Stratified by Previous Biologic Use at Week 12, NRI10

Abbreviations: Bio = biologic; ETN = etanercept; IXE = ixekizumab; NRI = nonresponder imputation; PASI = Psoriasis Area and Severity Index; Q2W = every 2 weeks; Q4W = every 4 weeks.

Note: p<.001 for all comparisons between IXE and ETN.

The median times to PASI 90 and PASI 100 for ixekizumab Q2W dosing were similar for patients with or without previous exposure to biologics (see Table 1).11

Table 1. Pooled UNCOVER-2 and -3: Median Time to PASI 90 and PASI 100 for Ixekizumab Every 2 Week Dosing in Patients With vs Without Prior Exposure to Biologics11


No Prior Biologic Use
N=594

Prior Biologic Use
N=142

PASI 90

8.4 (8.1-9.0)

8.1 (8.1-8.3)

PASI 100

13.1 (12.6-16.6)

12.3 (12.1-13.0)

Abbreviation: PASI = Psoriasis Area and Severity Index.

Data are median time (95% CI) in weeks.

UNCOVER-1 Secondary Analysis at Week 60

Responders, those with sPGA (0,1), to ixekizumab in the 12-week induction period of UNCOVER-1 were re-randomized to ixekizumab Q4W or placebo. Figure 2 demonstrates that patients who received ixekizumab maintained high levels of efficacy at week 60 regardless of previous biologic use.5

Figure 2. UNCOVER-1: PASI Response Rates Stratified by Previous Biologic Use at Week 60, NRI5

Abbreviations: Bio = biologic; IXE = ixekizumab; NRI = nonresponder imputation; PASI = Psoriasis Area and Severity Index; PBO = placebo; Q4W = every 4 weeks; sPGA = static Physician Global Assessment.

Notes:
p<.001 for all comparisons between IXE and PBO.
Analysis consists of patients with a clinical response (sPGA 0,1) to ixekizumab at week 12 and re-randomized to placebo or ixekizumab Q4W.

Prior Etanercept Use in UNCOVER-3

Figure 3 depicts PASI 75, PASI 90, and PASI 100 responses to ixekizumab treatment in patients with previous etanercept use in UNCOVER-3. This analysis included only those patients switching to ixekizumab Q4W following an initial 12-week treatment period with etanercept and 4-week placebo washout period.12

Figure 3. UNCOVER-3: PASI Response Rates in Patients who Received Etanercept During the 12-Week Induction Period Followed by Ixekizumab Q4W During Open-Label Extension Period, NRI12

Abbreviations: ETN = etanercept; IXE = ixekizumab; NRI = nonresponder imputation; PASI = Psoriasis Area and Severity Index; PBO = placebo; Q4W = every 4 weeks.
Note: Error bars=95% confidence intervals.

Previous Non-Biologic Systemic Therapy

An analysis of patients with prior use of non-biologic systemic therapies (including methotrexate, cyclosporine, retinoids, and psoralen/ultraviolet therapy) concluded that ixekizumab was effective irrespective of prior exposure to non-biologic systemic agents as shown in Figure 4.2

Figure 4. Pooled UNCOVER-1, -2, and -3: PASI Response Rates Stratified by Prior Non-biologic Treatment at Week 12, NRI2

Abbreviations: ETN = etanercept; IXE Q2W = ixekizumab every 2 weeks; IXE Q4W = ixekizumab every 4 weeks; NRI = nonresponder imputation; PASI = Psoriasis Area and Severity Index; PBO = placebo.
NOTE: ETN data is from UNCOVER-2 and UNCOVER-3 only.
* p<.05 vs PBO.
ǂ
p<.001 vs PBO (grey) and ETN (purple).

Ixekizumab Use in Secukinumab Non-Responders

An independent Canadian multicenter, retrospective study reviewed patients with moderate-to-severe plaque psoriasis previously treated with secukinumab 300 mg before beginning ixekizumab therapy.13

After 12 weeks of ixekizumab therapy, PASI 75 or PGA (0,1) was achieved in

  • 15/17 (88.2%) of patients that met study criteria

  •  4/4 (100%) secukinumab primary nonresponders

  • 8/9 (88.9%) secukinumab secondary nonresponders, and

  • 3/4 (75%) of patients who stopped secukinumab due to intolerance or non-drug related reasons.13

Duration of secukinumab therapy had no impact on ixekizumab efficacy outcomes.13

Additional independent retrospective reviews of ixekizumab efficacy following secukinumab therapy have been reported.13-17

References

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

2. Reich K, Menter A, Paul C, et al. Efficacy of ixekizumab in patients who have or have not received prior non-biologic systemic therapies: a pooled analysis of three phase 3 trials. Poster presented at: 5th International Congress of the Psoriasis International Network; July 7-9, 2016; Paris, France.

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

4. Papp KA, Leonardi CL, Blauvelt A, et al. Ixekizumab treatment for psoriasis: integrated efficacy analysis of three double-blinded, controlled studies (UNCOVER-1, UNCOVER-2, UNCOVER-3). Br J Dermatol. 2018;178(3):674-681. http://dx.doi.org/10.1111/bjd.16050

5. Gerdes S, Korman N, Wilhelm S, et al. Efficacy of ixekizumab in patients with plaque psoriasis, with and without previous exposure to biologic therapies: results at Weeks 12 and 60 from UNCOVER-1. Poster presented at: 24th Congress of the European Academy of Dermatology and Venereology; October 7-15, 2015; Copenhagen, Denmark.

6. Griffiths CE, Reich K, Lebwohl M, et al. 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. Supplementary Appendix. http://dx.doi.org/10.1016/S0140-6736(15)60125-8

7. 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

8. Gottlieb AB, Lacour JP, Korman N, Wilhelm S, et al. Treatment outcomes with ixekizumab in patients with moderate-to-severe psoriasis who have or have not received prior biological therapies: An integrated analysis of two phase iii randomized studies. J Eur Acad Dermatol Venereol. 2017;31(4):679-685. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412924/

9. Gottleib AB, Gerdes S, Lacour JP, et al. Ixekizumab in patients with moderate to severe psoriasis who have or have not received prior biologic therapies: an integrated analysis of 2 phase III studies. Poster presented at: 74th Annual Meeting of the American Academy of Dermatology; March 4-8, 2016; Washington, DC. https://server.aad.org/eposters/Submissions/getFile.aspx?id=3428&type=sub

10. Gottlieb AB, Lacour JP, Korman N, et al. Treatment outcomes with ixekizumab in patients with moderate-to-severe psoriasis who have or have not received prior biological therapies: an integrated analysis of two phase III randomized studies. J Eur Acad Dermatol Venereol. 2017;31(4):679-685. http://dx.doi.org/10.1111/jdv.13990

11. Pinter A, Langley R, See K, et al. Ixekizumab achieves rapid and high clearance in psoriasis patients with or without prior exposure to biologics. Poster presented at: 28th Annual Meeting of the European Academy of Dermatology and Venereology; October 9-13, 2019; Madrid, Spain.

12. Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of ixekizumab in patients previously treated with etanercept. Poster presented at: 25th Congress of the European Academy of Dermatology and Venereology; September 28-October 2, 2016; Vienna, Austria.

13. Georgakopoulos JR, Phung M, Ighani A, Yeung J. Efficacy and safety of switching to ixekizumab in secukinumab nonresponders with plaque psoriasis: a multicenter retrospective study of interleukin 17A antagonist therapies. J Am Acad Dermatol. 2018;79(1):155-157. http://dx.doi.org/10.1016/j.jaad.2018.01.003

14. Bokor-Billmann T, Schäkel K. No need to change the drug class: ixekizumab- following secukinumab-therapy in psoriasis [abstract]. J Dermatolog Treat. 2019;30(3):216-220. http://dx.doi.org/10.1080/09546634.2018.1506081

15. Conti A, Peccerillo F, Amerio P, et al. Efficacy and safety of switching to ixekizumab in secukinumab nonresponder patients with psoriasis: results from a multicentre experience. Br J Dermatol. 2019;180(6):1547-1548. http://dx.doi.org/10.1111/bjd.17580

16. Hegazy S, Konstantinou MP, Bulai Livideanu C, et al. Efficacy of ixekizumab in patients with resistance or incomplete response to secukinumab. J Eur Acad Dermatol Venereol. 2019;33(9):e338-e341. http://dx.doi.org/10.1111/jdv.15630

17. Sherman S, Cohen ES, Amitay-Laish I, et al. IL-17a inhibitor switching - efficacy of ixekizumab following secukinumab failure. A single-center experience. Acta Derm Venereol. 2019;99(9):769-773. http://dx.doi.org/10.2340/00015555-3200

Glossary

IL = interleukin

IL-17 = interleukin-17

PGA = Physician Global Assessment

PASI 75 = 75% improvement from baseline in Psoriasis Area and Severity Index

PASI 90 = 90% improvement from baseline in Psoriasis Area and Severity Index

PASI 100 = 100% improvement from baseline in Psoriasis Area and Severity Index

Q2W = every 2 weeks

Q4W = every 4 weeks

sPGA = static Physician Global Assessment

TNF = tumor necrosis factor

Datum fӧr senaste ӧversyn 2019 M09 18


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