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Table of Contents
CORRESPONDENCE
Year : 2021  |  Volume : 39  |  Issue : 2  |  Page : 87-88

Long-term effectiveness and safety of ixekizumab in the treatment of 14 patients with a history of chronic erythrodermic psoriasis who failed prior secukinumab: A bicentric retrospective study


1 Department of Dermatology, Cathay General Hospital, Taipei, Taiwan
2 Department of Dermatology, Chang Gung Memorial Hospital; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
3 Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

Date of Submission16-Aug-2020
Date of Decision18-Sep-2020
Date of Acceptance07-Oct-2020
Date of Web Publication18-May-2021

Correspondence Address:
Dr. Tsen-Fang Tsai
Department of Dermatology, National Taiwan University Hospital, National aiwan University College of Medicine, Taipei
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ds.ds_51_20

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How to cite this article:
Lo Y, Huang YH, Tsai TF. Long-term effectiveness and safety of ixekizumab in the treatment of 14 patients with a history of chronic erythrodermic psoriasis who failed prior secukinumab: A bicentric retrospective study. Dermatol Sin 2021;39:87-8

How to cite this URL:
Lo Y, Huang YH, Tsai TF. Long-term effectiveness and safety of ixekizumab in the treatment of 14 patients with a history of chronic erythrodermic psoriasis who failed prior secukinumab: A bicentric retrospective study. Dermatol Sin [serial online] 2021 [cited 2021 Sep 25];39:87-8. Available from: https://www.dermsinica.org/text.asp?2021/39/2/87/316298



Dear Editor,

Treatment of erythrodermic psoriasis (EP) is challenging because patients with current or history of EP are excluded in pivotal trials.[1] Ixekizumab and secukinumab are both interleukin (IL)-17A blockers. Ixekizumab has demonstrated effectiveness in patients with plaque type psoriasis and poor response to prior secukinumab and is especially effective in patients with secondary failure.[2],[3] The effectiveness of ixekizumab in EP up to week 12 has also been reported.[4] However, drug survival of biologics in EP is lower than in plaque psoriasis, and efficacy of ixekizumab peaks around 12–16 weeks. Thus, it is important to understand the long-term effectiveness of ixekizumab in EP.

In this bicentric retrospective study, we report our experience with ixekizumab in 14 patients with a history of chronic EP who had failed secukinumab. A chronic erythrodermic state was defined as a history of psoriatic plaque covering at least 80% of body surface area and lasting more than 12 weeks. Failure to reach 50% reduction of Psoriasis Area and Severity Index (PASI50) after administration of secukinumab for at least 12–16 weeks was defined as the primary failure to secukinumab. Ixekizumab was prescribed according to the package insert, and patients were followed for 60 weeks or until drug discontinuation. In Taiwan, PASI50 responses at 24 weeks and beyond were required for reimbursement.

This is a long-term follow-up of our previous case series with additional five new cases [Table 1].[4] Our data indicated that ixekizumab showed an early response at week 4 with eight (57.1%) and five (35.7%) patients achieving PASI75 and PASI90 responses, respectively. Two patients (14.3%) achieved PASI100 at weeks 8 and 12. However, as early as 32 weeks, two patients (14.3%) discontinued ixekizumab due to the disease worsening above the baseline [Figure 1]. Among the nine (64.3%) patients still using ixekizumab at week 52, PASI50, PASI75, and PASI90 responses were achieved by six (42.9%), four (28.6%), and one (7.1%) patient, respectively. At week 60, only five (35.7%) patients continued taking ixekizumab, and only one patient achieved PASI75 response. Effect of treatment was lower than a previous long-term follow-up study in Japan.[5]
Table 1: Summary of the 14 cases of erythrodermic psoriasis

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Figure 1: Percentage of PASI responders of the 14 cases of erythrodermic psoriasis.

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In contrast to the prior results in plaque-type psoriasis,[5] a much higher discontinuation rate was observed in our series at week 52. Patients with EP were known to respond less favorably to biologics, and the result may be further compromised in our patients since all of our patients had failed multiple prior biologics. The average number was 3.14 ± 1.03 (mean ± standard deviation); the range was from 1 to 5. In addition, based on the previous study, higher use of prior biologics could be a predictive factor of lower drug survival with subsequent biologics.[6],[7] Among the four patients who were primary failures to secukinumab, one patient showed a primary failure to ixekizumab, and none achieved PASI75 at week 16. In contrast, among the ten patients who were secondary failures to secukinumab, none of them had a primary failure to ixekizumab, and seven (70%) achieved PASI75 response at week 16. The result was similar to a previous study[3] that primary failure to secukinumab predicted poor response to subsequent ixekizumab treatment. The possible explanation may be related to the shared mode of action of secukinumab and ixekizumab. However, no specific risk factors were found between primary and secondary failure group, possibly due to the small sample size.

Injection-site reaction is common during ixekizumab treatment. In our series, five (35.7%) patients complained of injection-site swelling which lasted for 1–7 days. According to the real-world data from Spain,[7] 14% of patients complained of injection-site discomfort, which was also higher than the original Phase III trial. In addition, three (21.4%) patients complained of diarrhea, and two (14.3%) patients noticed new-onset urticaria. One patient had severe vulvovaginal candidiasis, a known adverse effect of ixekizumab.[8]

In conclusion, a rapid, but not sustained, the response was seen in most of our cases treated with ixekizumab. The optimal dosing and frequency of ixekizumab for patients with EP await further studies.

Financial support and sponsorship

Nil.

Conflicts of interest

Prof. Tsen-Fang Tsai, an editorial board member of Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.



 
  References Top

1.
Hsu SH, Tsai TF. Evolution of the inclusion/exclusion criteria and primary endpoints in pivotal trials of biologics and small oral molecules for the treatment of psoriasis. Expert Rev Clin Pharmacol 2020;13:211-32.  Back to cited text no. 1
    
2.
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;79:155-7.  Back to cited text no. 2
    
3.
Amschler K, Phillip S, Mohr J, Wilsmann-Theis D, Poortinga S, Gerdes S, et al. Long-term follow-up of 22 psoriatic patients treated with ixekizumab after failure of secukinumab. Dermatol Online J 2020;26:2.  Back to cited text no. 3
    
4.
Lo Y, Tsai TF. Clinical experience of ixekizumab in the treatment of patients with history of chronic erythrodermic psoriasis who failed secukinumab: A case series. Br J Dermatol 2019;181:1106-7.  Back to cited text no. 4
    
5.
Okubo Y, Mabuchi T, Iwatsuki K, Elmaraghy H, Torisu-Itakura H, Morisaki Y, et al. Long-term efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis: Subgroup analyses of an open-label, Phase 3 study (UNCOVER-J). J Eur Acad Dermatol Venereol 2019;33:325-32.  Back to cited text no. 5
    
6.
Ger TY, Huang YH, Hui RC, Tsai TF, Chiu HY. Effectiveness and safety of secukinumab for psoriasis in real-world practice: Analysis of subgroups stratified by prior biologic failure or reimbursement. Ther Adv Chronic Dis 2019;10:2040622319843756.  Back to cited text no. 6
    
7.
Deza G, Notario J, Lopez-Ferrer A, Vilarrasa E, Ferran M, Del Alcazar E, et al. Initial results of ixekizumab efficacy and safety in real-world plaque psoriasis patients: A multicentre retrospective study. J Eur Acad Dermatol Venereol 2019;33:553-9.  Back to cited text no. 7
    
8.
Papp KA, Bachelez H, Blauvelt A, Winthrop KL, Romiti R, Ohtsuki M, et al. Infections from seven clinical trials of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriasis. Br J Dermatol 2017;177:1537-51.  Back to cited text no. 8
    


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