Taltz ® (ixekizumab) injektion

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Taltz® (ixekizumab): Effekt hos nagelpsoriasis

Nagelpsoriasis visade signifikant större förbättring vid vecka 12 med ixekizumab jämfört med placebo och etanercept.

Background Information

Significantly greater improvements at week 12 from baseline compared to placebo and etanercept were demonstrated in

  • nail psoriasis (as measured by the Nail Psoriasis Severity Index [NAPSI])

and were maintained at week 60 in patients treated with Taltz who were sPGA (0,1) responders at week 12.1

Efficacy in fingernail psoriasis, measured using NAPSI, was a secondary endpoint in all 3 UNCOVER trials.2 To calculate NAPSI, each fingernail is divided into quadrants and evaluated for the presence (1) or absence (0) of fingernail bed psoriasis and matrix psoriasis (range 0-8 per fingernail). The total NAPSI score is the sum of the 10 individual nail scores and ranges from 0 (no nail psoriasis) to 80 (severe nail psoriasis).3

Up to 82% of patients with psoriasis have disease that affects the fingernails.4-6

 provides brief descriptions of the clinical trials included in this response.

Please note that dosing schedules are mentioned in this statement that are not consistent with the approved dosing schedule for plaque psoriasis in the Taltz summary of product characteristics. Please refer to the Taltz summary of product characteristics for approved dosing.1

Fingernail Psoriasis Efficacy

UNCOVER-1, -2, and -3: Week 12

 depicts complete fingernail resolution (NAPSI=0) at week 12 in patients with baseline fingernail psoriasis in UNCOVER-1, -2, and -3. A numerically higher percentage of patients treated with ixekizumab achieved NAPSI=0 than patients receiving placebo in all 3 trials and this difference was statistically significant (p<.001 vs placebo) for both ixekizumab Q2W and Q4W in UNCOVER-1 and -3.3,7 Because nail growth is slow, 12 weeks may be insufficient to observe the full effect of treatment on nail psoriasis. Therefore, NAPSI scores were also assessed at later time points in the UNCOVER trials.3

Table 1. UNCOVER-1, -2, and -3: Complete Fingernail Psoriasis Resolution at Week 12 in Patients With Baseline Fingernail Psoriasis (NAPSI>0), NRI3,7,8


UNCOVER-1

UNCOVER-1

UNCOVER-1

UNCOVER-2

UNCOVER-2

UNCOVER-2

UNCOVER-2

UNCOVER-3

UNCOVER-3

UNCOVER-3

UNCOVER-3


PBO
N=283
%

IXE Q4W
N=283
%

IXE Q2W
N=284
%

PBO
N=113
%

ETN
N=229
%

IXE Q4W
N=219
%

IXE Q2W
N=209
%

PBO
N=116

%

ETN
N=236
%

IXE Q4W
N=228
%

IXE Q2W
N=229
%

NAPSI=0

3.5

12.7a

16.9a

8.8

10.5

12.3

15.3

4.3

10.2

19.7ab

17.5ab

Abbreviations: ETN = etanercept; IXE = ixekizumab; NAPSI = Nail Psoriasis Severity Index; NRI = nonresponder imputation; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

a p<.001 vs placebo.

b p<.05 vs etanercept.

UNCOVER-3: Week 60

Figure 1 shows response rates for mean percent NAPSI improvement through week 60 in patients with baseline fingernail psoriasis (NAPSI>0) in UNCOVER-3.

In the long-term extension period of UNCOVER-3 through week 60, the percentage of patients with complete fingernail psoriasis resolution (NAPSI=0) continued to improve. For the approved moderate-to-severe psoriasis ixekizumab dosing regimen (ixekizumab 80 mg Q2W through week 12 following a 160-mg starting dose at week 0 then 80 mg Q4W after week 12), the percentage of patients with NAPSI=0 at week 60 was 62.4% and these improvements were comparable regardless of patient treatment assignment during the induction dosing period (data are not shown).3

Figure 1. UNCOVER-3: NAPSI Percent Improvement From Baseline Responses Through Week 60 in Patients With Baseline Fingernail Psoriasis, MMRM3

Abbreviations: ETN = etanercept; IXE = ixekizumab; LSM = least squares mean; MMRM = mixed-model repeated measures; NAPSI = Nail Psoriasis Severity Index; OLE = open-label extension; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

Note: Dotted line represents 4-week washout period. Patients switched from ETN received IXE starting at week 16.

* p≤.05 vs PBO.

p≤.05 vs ETN.

UNCOVER-1 and -3: Long-term Efficacy

Figure 2 and Figure 3 show long-term fingernail efficacy responses in patients with baseline fingernail psoriasis receiving the approved ixekizumab dosing regimen. In both studies, the authors concluded that the high fingernail psoriasis efficacy results were sustained through 5-year, long-term treatment with ixekizumab.9,10

Figure 2. UNCOVER-1: Complete Resolution of Fingernail Psoriasis (NAPSI=0) From Week 60 Through Week 264 in Patients With Baseline Fingernail Psoriasis, Observed Cases9

Abbreviation: NAPSI = Nail Psoriasis Severity Index.

Figure 3. UNCOVER-3: Complete Resolution of Fingernail Psoriasis (NAPSI=0) Through Week 264 in Patients With Baseline Fingernail Psoriasis10,11

Abbreviations: IXE = ixekizumab; Q2W = every 2 weeks; Q4W = every 4 weeks; MI = multiple imputation; mNRI = modified nonresponder imputation; NAPSI = Nail Psoriasis Severity Index.

UNCOVER-3: Post Hoc Analysis in Patients With Significant Nail Involvement

In UNCOVER-3, an additional post-hoc analysis was conducted in the subset of patients with significant nail involvement at baseline (defined as fingernail NAPSI≥16 and involvement of at least 4 fingernails; n=491).12 At week 12, the mean NAPSI improvement in patients treated with

  • ixekizumab Q2W was 39%

  • ixekizumab Q4W was 40%

  • etanercept 50 mg twice weekly was 28%, and

  • placebo was -5% (worsening of fingernail psoriasis).12

For those patients on ixekizumab Q2W dosing in the induction period who continued on Q4W dosing beginning at week 12, the mean NAPSI improvement was 86% at week 60 and complete resolution of nail disease (NAPSI=0) was observed in 56% of those patients at week 60.12

IXORA-S: Week 52

IXORA-S was a phase 3b, multicenter, randomized (1:1), double-blind, parallel-group, head-to-head study comparing ixekizumab to ustekinumab in patients with moderate-to-severe plaque psoriasis.13 In IXORA-S, patients with baseline fingernail psoriasis were assessed for improvements in NAPSI scores through 52 weeks.14

Table 2 shows progressive improvement in NAPSI scores that was observed in both groups, with complete resolution of nail psoriasis occurring in a significantly greater percentage of patients treated with ixekizumab compared with ustekinumab at week 16 (p=.02) and through week 52 (p<.001).14

Table 2. IXORA-S: Efficacy in Nail Lesions at Weeks 16 and 52 in Patients With Baseline Fingernail Psoriasis14,15

 

Ustekinumab

Ixekizumab

Patients with NAPSI >0, n (%) 

105 (63.3) 

84 (61.8) 

Baseline NAPSI total score, mean (SD) 

24.8 (20.0) 

28.3 (19.9) 

Week 16 NAPSI=0 by NRI, n (%)

17 (16.2)

26 (31.0)a

Week 52 NAPSI=0 by NRI, n (%)

30 (28.6)

52 (61.9)b

NAPSI change from baseline at week 52 by mBOCF, LSM (95% CI)

-15.6 (-17.8, -13.4)

-22.4 (-24.8, -20.0)b

Abbreviations: LSM = least squares mean; mBOCF = modified baseline observation carried forward; NAPSI = nail psoriasis severity index; NRI = nonresponder imputation; UST = ustekinumab.

a p=.02 vs UST.

b p<.001 vs UST.

References

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

2. 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

3. van de Kerkhof P, Guenther L, Gottlieb AB, et al. Ixekizumab treatment improves fingernail psoriasis in patients with moderate-to-severe psoriasis: results from the randomized, controlled and open-label phases of UNCOVER-3. J Eur Acad Dermatol Venereol. 2017;31(3):477-482. http://dx.doi.org/10.1111/jdv.14033

4. de Jong EM, Seegers BA, Gulinck MK, et al. Psoriasis of the nails associated with disability in a large number of patients: results of a recent interview with 1,728 patients. Dermatology. 1996;193(4):300-303. http://www.ncbi.nlm.nih.gov/pubmed/8993953

5. Klaassen KMG, van de Kerkhof PCM, Pasch MC. Nail psoriasis, the unknown burden of disease. J Eur Acad Dermatol Venereol. 2014;28(12):1690-1695. http://dx.doi.org/10.1111/jdv.12368

6. Rich P, Griffiths C, Reich K, et al. Baseline nail disease in patients with moderate to severe psoriasis and response to treatment with infliximab during 1 year. J Am Acad Dermatol. 2008;58(2):224-231. http://dx.doi.org/10.1016/j.jaad.2007.07.042

7. Guenther L, Sebastian M, Wu J, et al. Impact of ixekizumab treatment on fingernail psoriasis: results from UNCOVER-1. Poster presented at: 24th European Academy of Dermatology and Venereology (EADV) Congress; October 7-11, 2015; Copenhagen, Denmark.

8. van de Kerkhof P, Guenther L, Gottlieb A, et al. Improvement in fingernail lesions in patients with moderate-to-severe psoriasis treated with ixekizumab versus placebo and etanercept: results from UNCOVER-2. Poster presented at: 74th Annual Meeting of the American Academy of Dermatology; March 4-8, 2016; Washington, DC.

9. Papp K, Gerdes S, Elmaraghy H, et al. Sustained high efficacy and a favorable safety profile in hard-to-treat areas in patients with moderate-to-severe psoriasis: five year results from a phase 3 trial. Poster presented at: 28th Annual Meeting of the European Academy of Dermatology and Venereology (EADV); October 9-13, 2019; Madrid, Spain.

10. Blauvelt A, Lebwohl MG, Mabuchi T, et al. Long-term efficacy and safety of ixekizumab: 5-year analysis of the UNCOVER-3 randomized controlled trial. J Am Acad Dermatol. Published online November 28, 2020. http://dx.doi.org/10.1016/j.jaad.2020.11.022

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

12. Dennehy EB, Zhang L, Amato D, et al. Ixekizumab is effective in subjects with moderate to severe plaque psoriasis with significant nail involvement: results from UNCOVER 3. J Drugs Dermatol. 2016;15(8):958-961. http://jddonline.com/articles/dermatology/S1545961616P0958X/1

13. Reich K, Pinter A, Lacour JP, et al. Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study. Br J Dermatol. 2017;177(4):1014-1023. http://dx.doi.org/10.1111/bjd.15666

14. Wasel N, Thaçi D, French LE, et al. Ixekizumab and ustekinumab efficacy in nail psoriasis in patients with moderate-to-severe psoriasis: 52-week results from a phase 3, head-to-head study (IXORA-S). Dermatol Ther (Heidelb). 2020;10(4):663-670. https://doi.org/10.1007/s13555-020-00383-x

15. Wasel N, Dutronc Y, Schinzel B, Lacour JP. Comparison of ixekizumab and ustekinumab efficacy in the treatment of nail lesions of patients with moderate-to-severe plaque psoriasis: 52-week data from the IXORA-S trial. Abstract presented at: 27th Congress of the European Academy of Dermatology and Venereology (EADV); September 12-16, 2018; Paris, France.

16. Paul C, Griffiths CE, van de Kerkhof PC, et al. Ixekizumab provides superior efficacy compared to ustekinumab over 52-weeks of treatment: results from IXORA-S, a phase 3 study. J Am Acad Dermatol. 2019;80(1):70-79.e3. https://doi.org/10.1016/j.jaad.2018.06.039

Glossary

NAPSI = Nail Psoriasis Severity Index

Q2W = every 2 weeks

Q4W = every 4 weeks

Appendix A: Clinical Trial Designs

Figure 4. Study Design of Induction (UNCOVER-1, -2, and -3) and Maintenance (UNCOVER-1 and -2) Dosing Periods2

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.

Notes:
Etanercept arm was not included in UNCOVER-1.

Responders (sPGA 0 or 1) to ixekizumab at week 12 were rerandomized to receive IXE Q4W, IXE Q12W, or PBO.

In UNCOVER-2 study, nonresponders to ETN at week 12 were switched to IXE Q4W (without a 160-mg starting dose) after a 4‑week washout period.

Nonresponders to PBO at week 12 received a 160-mg starting dose of ixekizumab followed by IXE Q4W.

(dotted line) indicates relapse (sPGA ≥3).

UNCOVER-3 study is not represented in maintenance period design as the extension period consisted of open-label treatment with IXE Q4W.

Figure 5. IXORA-S: Clinical Trial Design16

Abbreviations: IXE = ixekizumab; Q2W = every 2 weeks; Q4W = every 4 weeks; R = randomization; UST = ustekinumab.

Datum fӧr senaste ӧversyn 2020 M12 07


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