Journal Information
Vol. 109. Issue 6.
Pages 565-567 (July - August 2018)
Vol. 109. Issue 6.
Pages 565-567 (July - August 2018)
Case and Research Letters
DOI: 10.1016/j.adengl.2018.05.005
Full text access
Response to Secukinumab after Treatment Failure with Ustekinumab in 6 Patients with Plaque Psoriasis
Respuesta a secukinumab tras fracaso terapéutico con ustekinumab en seis pacientes con psoriasis en placas
Visits
...
D. Morgado-Carrasco, J. Riera-Monroig, X. Fustà-Novell, M. Alsina Gibert
Corresponding author
malsina@clinic.cat

Corresponding author.
Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain
Article information
Full Text
Bibliography
Download PDF
Statistics
Figures (1)
Tables (2)
Table 1. Clinical and Epidemiological Characteristics of the Patients.
Table 2. Response to Secukinumab in Patients with Plaque Psoriasis Following Treatment Failure With Ustekinumab.
Show moreShow less
Full Text
To the Editor:

Secukinumab (SEC) and ustekinumab (UST) are monoclonal antibodies that have both been shown to be highly effective in the treatment of psoriasis,1 although in pivotal studies SEC achieved higher rates of efficacy.2 Their mechanisms of action differ in the target each one blocks in the inflammatory cascade: SEC is an interleukin (IL)-17 inhibitor, while UST blocks IL-12 and IL-23. Clinical trials have demonstrated the efficacy of SEC in patients previously treated with other systemic drugs, including monoclonal antibodies that inhibit tumor necrosis factor (TNF).3 However, to date there have been no publications about its effectiveness following treatment failure with UST.

Our aim in this study was to assess the efficacy of SEC in patients who had experienced primary or secondary treatment failure with UST, defined respectively as a failure to achieve a 75% reduction in baseline Psoriasis Area and Severity Index (PASI 75) at week 12 or the subsequent loss of such a response. The primary objective was to assess whether patients on SEC had achieved, by week 12, a 90% reduction in baseline PASI (a PASI 90 response), a Physician Global Assessment (PGA) of 1 or less (clear or almost clear), and a Dermatology Life Quality Index (DLQI) of 5 or less. The secondary objective was to assess whether the response was maintained at week 24.

We retrospectively evaluated 6 cases of patients with plaque psoriasis and an inadequate response to prior treatment with UST who were treated with the SEC regimen specified in the Summary of Product Characteristics (complete induction and maintenance with 300mg every 4 weeks). PASI, PGA, and DLQI were measured at baseline and at weeks 12 and 24.

The clinical and epidemiological characteristics of the patients are shown in Table 1. We studied 6 men aged between 32 and 61 years (median, 51 years) with a history of psoriasis of more than 10 years duration (median, 16 years).

Table 1.

Clinical and Epidemiological Characteristics of the Patients.

Sex  Age, y  Weight, kg  BMI, kg/m2  Smoking  Years With Psoriasis  Psoriatic Arthritis  Comorbid Conditions  Prior Systemic Treatment 
46  107  32.0  Yes  26  No  Microscopic colitis, chronic obstructive pulmonary disease, hypertension, heart failure  CIC, MTX 
61  90  29.7  No  17  No  None  CIC, MTX, ACI, anti-TNF 
58  61  25.1  No  16  Yes  High blood pressure, osteoporosis  Leflunomide, anti-TNF 
56  85  28.1  No  16  No  None  CIC, MTX, ACI 
32  93  30.7  Yes  10  No  None  MTX 
35  75  25.9  Yes  11  No  Bronchial asthma, paroxysmal positional vertigo  CIC 

Abbreviations: ACI, acitretin; anti-TNF: monoclonal antibody targeting tumor necrosis factor; CIC: ciclosporin; M: man; MTX: methotrexate.

Table 2 shows the response to treatment with UST and SEC. Treatment failure with UST was primary in 4 patients and secondary in 2. The patients’ PASI scores before starting treatment with SEC ranged from 3.2 to 21 (median, 12.6), the PGA from 3 to 4 (median, 3) and the DLQI from 2 to 25 (median, 13.5). None of the patients received concomitant treatments in addition to SEC. All of the patients presented a reduction in disease activity at week 12 (Fig. 1): PASI 90 in 66.7% (4/6), and PGA and DLQI of 1 or less in 83.3% (5/6). SEC was withdrawn in 1 patient who did not achieve a PASI 50 response. At week 24, 33.3% (2/6) of the patients had a PASI 90 response, 66.6% (4/6) achieved PASI 75, 50% (3/6) had an absolute PASI of less than 3, and 66.6% (4/6) a PGA and DLQI of less than 1. No significant adverse events were observed during the 24 weeks of treatment with SEC.

Table 2.

Response to Secukinumab in Patients with Plaque Psoriasis Following Treatment Failure With Ustekinumab.

Treatment With USTBefore Start of SECSEC Week 12SEC Week 24
Prior PASI  PASI week 12  Failure on UST  PASI  DLQI  PGA  PASI  PASI 90  DLQI  PGA  PASI  PASI 90  DLQI  PGA 
39  11.9  Primary*  21  22  Yes  13  6.3  No  13 
43.5  9.1  Secondary**  11.8  9.4  No  NT  NT  NT  NT 
9.1  8.4  Primary*  16.7  1.2  Yes  3.2  No 
22.1  Secondary**  13.3  25  3.1  No  2.2  No 
18  4.8  Primary*  6.1  19  Yes  Yes 
3.2  Primary*  3.2  Yes  Yes 

Abbreviations: DLQI, Dermatology Life Quality Index; NT, treatment withdrawn due to lack of response. (failure to achieve PASI 50 by week 12); PASI, Psoriasis Area and Severity Index; PGA, Physician Global Assessment; SEC, secukinumab; UST, ustekinumab.

*

Primary failure: failure to achieve a reduction of 75% over baseline PASI (PASI 75) at week 12.

**

Secondary failure: loss of PASI 75 response after week 12.

Figure 1.

Response to treatment with secukinumab in patients with an unacceptable response to treatment with ustekinumab.PASI, Psoriasis Area and Severity Index; SEC, secukinumab.

(0.14MB).

In this series of 6 patients in whom treatment with UST had not achieved an acceptable response, 4 patients achieved the primary treatment goal with SEC at week 12. Only 2 patients maintained a PASI 90 response at week 24 (the secondary objective). We used a PASI 90 response as an indicator in line with the current trend towards setting more demanding goals with new biologic therapies. However, most of the patients achieved a PASI 75 response and a PGA 1 or less at weeks 12 and 24, and reported significant improvement in quality of life, reflected by a reduction in DLQI in almost all cases.

The results obtained with SEC were not as good as those reported in the pivotal studies,2,3 a difference that may be due to the inclusion of patients who had previously failed to respond to several systemic therapies, an indication that their condition was difficult to manage. Another possible explanation might be found in the mechanism of action since by inhibiting IL-23, UST indirectly inhibits IL-17.4 Consequently, patients who had failed to respond to UST had already experienced some degree of blockade of the pro-inflammatory IL targeted by SEC without an acceptable clinical response. To further explore this hypothesis, it would be important to assess the response to SEC in patients who fail to respond to treatment with TNF antagonists, which do not inhibit IL-17. However, we found no publications relating to this clinical situation. In the pivotal trials of SEC, fewer than 10% of patients had previously failed to respond to anti-TNF therapy,2,3 and the data relating to this subgroup was unfortunately not analyzed.

Finally, we did not identify any predictors of response to SEC following treatment failure with UST.

The main strengths of this study were the use of multiple clinical response criteria (PASI, PGA and DLQI) before and during biologic therapy and follow-up of the response at 24 weeks. The main limitations were the retrospective nature of the study and the small number of patients included.

In conclusion, SEC can be an alternative treatment option in patients who have failed to respond to treatment with UST.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Références
[1]
A. Nast, A. Jacobs, S. Rosumeck, R.N. Werner.
Efficacy and safety of systemic long-term treatments for moderate-to-severe psoriasis: A systematic review and meta-analysis.
J Invest Dermatol., 135 (2015), pp. 2641-2648
[2]
D. Thaçi, A. Blauvelt, K. Reich, T.-F. Tsai, F. Vanaclocha, K. Kingo, et al.
Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial.
J Am Acad Dermatol., 73 (2015), pp. 400-409
[3]
R.G. Langley, B.E. Elewski, M. Lebwohl, K. Reich, C.E.M. Griffiths, K. Papp, et al.
Secukinumab in plaque psoriasis —results of two phase 3 trials.
N Engl J Med., 371 (2014), pp. 326-338
[4]
S.L. Gaffen, R. Jain, A.V. Garg, D.J. Cua.
The IL-23-IL-17 immune axis: From mechanisms to therapeutic testing.
Nat Rev Immunol., 14 (2014), pp. 585-600

Please cite this article as: Morgado-Carrasco D, Riera-Monroig J, Fustà-Novell X, Gibert MA. Respuesta a secukinumab tras fracaso terapéutico con ustekinumab en seis pacientes con psoriasis en placas. Actas Dermosifiliogr. 2018;109:565–567.

Copyright © 2017. Elsevier España, S.L.U. and AEDV
Idiomas
Actas Dermo-Sifiliográficas (English Edition)

Subscribe to our newsletter

Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?