Key Words: Plaque psoriasis, biological treatments, secukinumab, Epistemonikos, GRADE.
INTRODUCTION
Biological treatments have appeared as the main alternative for the management of patients with plaque psoriasis that do not respond to conventional treatment. So, evaluating its actual efficacy and safety is needed.
METHODS
We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.
RESULTS AND CONCLUSIONS
We identified 21 systematic reviews including ten studies overall, of which all were randomized trials. We concluded secukinumab achieves clinical improvement in patients with plaque psoriasis, although it is probably associated with serious adverse effects.
Approximately 20% of patients with plaque psoriasis have moderate to severe disease [1], requiring conventional systemic treatment, such as methotrexate, cyclosporine or acitretin, or phototherapy. However, for a large number of patients, these treatments are not sufficient, due to a limited therapeutic effect or to the presence of adverse effects.
In the search for more effective and safe treatments, biological therapies have emerged in the last years as an alternative. Secukinumab is a human monoclonal antibody that selectively neutralizes interleukin-17A, which has a major role in the pathogenesis of psoriasis. We aimed to evaluate the efficacy and safety of secukinumab in patients with plaque psoriasis.
We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others, to identify systematic reviews and their included primary studies. We extracted data from the identified reviews and reanalyzed data from primary studies included in those reviews. With this information, we generated a structured summary denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos) using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies when it is possible, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.
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Key messages
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What is the evidence. |
We found 21 systematic reviews [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22] that included ten primary studies, reported in 23 references [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], all corresponding to randomized controlled trials. However, four of these trials were excluded from our analysis: two because the intervention was not administered in usual doses [27], [39] and two because no comparison was made against placebo [32], [33], [34], [44], [45]. This table and the summary in general are based on the six randomized trials that answer the question of interest [23], [28], [31], [35], [37], [40]. |
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What types of patients were included* |
All trials included adult patients older than 18 years with plaque psoriasis on the trunk, upper and lower limbs, not including scalp, with moderate to severe disease determined by PASI ≥ 12, IGA 3-4, BSA ≥ 10%, without response to topical treatment, phototherapy or conventional systemic treatment. Two trials [23], [37] excluded patients who had received biological treatment with anti-interleukin-17. |
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What types of interventions were included* |
Four trials [23], [28], [31], [37] included subcutaneous secukinumab 150 mg or 300 mg weekly for four weeks and then in monthly doses. One trial [35] included an intervention group with subcutaneous secukinumab 150 mg at weeks 0,4 and 8. Another trial [40] included three intervention groups: subcutaneous secukinumab 150 mg in single dose; subcutaneous secukinumab 150 mg at weeks 0,4 and 8; and subcutaneous secukinumab 150 mg at weeks 0, 1, 2 and 4. |
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What types of outcomes |
The trials evaluated multiple outcomes, which were grouped in the systematic reviews as follows:
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* The information about primary studies is extracted from the systematic reviews identified, unless otherwise specified.
The information about the effects of secukinumab is based on six randomized trials including 2531 patients [23], [28], [31], [35], [37], [40].
All trials reported PASI 75 and PGA/IGA (2531 patients) [23], [28], [31], [35], [37], [40]. Five trials reported PASI 90 and serious adverse events (2482 patients) [23], [28], [31], [37], [40]. Two trials reported DLQI (1708 patients) [28], [31].
The summary of findings is as follows:

| Follow the link to access the interactive version of this table (Interactive Summary of Findings – iSoF) |

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To whom this evidence does and does not apply |
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| About the outcomes included in this summary |
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| Balance between benefits and risks, and certainty of the evidence |
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| Resource considerations |
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| What would patients and their doctors think about this intervention |
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Differences between this summary and other sources |
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| Could this evidence change in the future? |
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Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Secukinumab for plaque psoriasis.
The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier.
After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.
This article is part of the Epistemonikos Evidence Synthesis project. It is elaborated with a pre-established methodology, following rigorous methodological standards and internal peer review process. Each of these articles corresponds to a summary, denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos), whose main objective is to synthesize the body of evidence for a specific question, with a friendly format to clinical professionals. Its main resources are based on the evidence matrix of Epistemonikos and analysis of results using GRADE methodology. Further details of the methods for developing this FRISBEE are described here (http://dx.doi.org/10.5867/medwave.2014.06.5997)
Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).
Potential conflicts of interest
The authors do not have relevant interests to declare.
Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.
INTRODUCCIÓN
Los tratamientos biológicos han aparecido como principal alternativa para el manejo de los pacientes con psoriasis en placa que no responden a tratamiento convencional, resultando necesario evaluar su real efectividad y seguridad.
MÉTODOS
Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE.
RESULTADOS Y CONCLUSIONES
Identificamos 21 revisiones sistemáticas que en conjunto incluyeron diez estudios primarios, todos correspondientes a ensayos aleatorizados. Concluimos que secukinumab logra mejoría clínica en pacientes con psoriasis en placa, aunque probablemente se asocia a efectos adversos graves.
Authors:
Gonzalo Ordenes-Cavieres[1,2], Romina Andino-Navarrete[2,3]
Citation: Ordenes-Cavieres G, Andino-Navarrete R. Secukinumab for plaque psoriasis. Medwave 2018;18(7):e7363 doi: 10.5867/medwave.2018.07.7363
Submission date: 6/11/2018
Acceptance date: 27/11/2018
Publication date: 30/11/2018
Origin: This article is a product of the Evidence Synthesis Project of Epistemonikos Fundation, in collaboration with Medwave for its publication.
Type of review: Non-blinded peer review by members of the methodological team of Epistemonikos Evidence Synthesis Project.
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