DNA copy number variation associated with anti-tumour necrosis factor drug response and paradoxical psoriasiform reactions in patients with moderate-to-severe psoriasis

Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30–50% of patients do not respond to these drugs and may even develop paradoxical psoriasiform reactions. This study search-ed for DNA copy number variations that could predict anti-tumour necrotic factor drug response or the ap-pearance of anti-tumour necrotic factor induced pso-riasiform reactions. Peripheral blood samples were collected from 70 patients with anti-tumour necrotic factor drug-treated moderate-to-severe plaque pso-riasis. Samples were analysed with an Illumina 450K methylation microarray. Copy number variations were obtained from raw methylation data using conumee and Chip Analysis Methylation Pipeline (ChAMP) R packa-ges. One copy number variation was found, harbouring one gene (CPM) that was significantly associated with adalimumab response (Bonferroni-adjusted p-value < 0.05). Moreover, one copy number variation was identified harbouring 3 genes (ARNT2, LOC101929586 and MIR5572) related to the development of paradoxical psoriasiform reactions. In conclusion, this study has identified DNA copy number variations that could be good candidate markers to predict response to ada-limumab and the development of anti-tumour necrotic factor paradoxical psoriasiform reactions.This study was supported by Instituto de Salud Carlos III PI 13/01598 and the Ministry of Science and Innovation and the European Regional Development’s funds (FEDER). Conflicts of interest. FA-S has been a consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Chemo, Farmalíder, Ferrer, GlaxoSmithKline, Gilead, Janssen-Cilag, Kern, Normon, Novartis, Servier, Teva, and Zambon. ED has potential conflicts of interest (advisory board member, consultant, grants, research support, participation in clinical trials, honoraria for speaking, and research support) with the following pharmaceutical companies: AbbVie (Abbott), Amgen, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, MSD, Lilly and Celgene. ML-V has potential conflicts of interest as she has participated in clinical trials or as consultant with Abbvie (Abbott), Galderma, Janssen-Cilag, Leo Pharma, Pfizer, Novarties, Lilly, Almirall and Celgene. MCO-B has potential conflicts of interest (honoraria for speaking and research support) with Janssen-Cilag and Leo Pharma. The other authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. AS-T has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Novartis and Pfizer. RB-E has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Novartis and Pfizer

Effect of sex in systemic psoriasis therapy: Differences in prescription, effectiveness and safety in the BIOBADADERM prospective cohort

The effect of sex on systemic therapy for psoriasis has not been well studied. The aim of this study was to analyse a large multicentre Spanish cohort of 2,881 patients with psoriasis (58.3% males), followed from January 2008 to November 2018, to determine whether sex influences prescription, effectiveness of therapy, and the risk of adverse events. The results show that women are more likely than men to be pre-scribed biologics. There were no differences between men and women in effectiveness of therapy, measur-ed in terms of drug survival. Women were more likely to develop adverse events, but the difference in risk was small and does not justify different management. Study limitations include residual confounding and the use of drug survival as a proxy for effectiveness.The BIOBADADERM project is promoted by the Fundación Piel Sana Academia Española de Dermatología y Venereología, which receives financial support from the Spanish Medicines and Health Products Agency (Agencia Española de Medicamentos y Productos Sanitarios) and from pharmaceutical companies (Abbott/Abbvie, Pfizer, MSD, Novartis, Lilly, Janssen and Almirall)

La prevalencia de diez enfermedades inflamatorias inmunomediadas (IMID) en España

Background: Immune-mediated inflammatory diseases (IMID) are chronic and highly disabling diseases that share inflammatory sequences and immunological dysregulations. Considered as a disease in itself, the pre- valence of IMID is virtually unknown. The aim of this study was to assess the prevalence of 10 selected UDI, including rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, systemic lupus erythematosus, hidradenitis suppurativa, sarcoidosis and uvei- tis in Spain. Methods: A cross-sectional epidemiological study of point prevalen- ce was made. This study was carried out through a series of computerized interviews in households chosen at random in 17 autonomous communities in Spain. A structured questionnaire was used to determine the frequency of diagnosis and the concurrence of 10 IMID in the respondents and other indi- viduals belonging to the same family nucleus. The point prevalence estimates were used and compared with the objective of determining the frequency of IMID by age, sex and communities. The data were processed using Excel 2016 (Microsoft, Redmond, WA, USA) and the SPSS V.019 system (IBM Corp. Armonk, NY, USA) for statistical analysis using the usual statistical tests in this type of studies. Results: Of the 7,980 respondents, 510 were diagnosed with an IMID, representing a cross-sectional study of 6.39% (95% CI: 6.02-6.76). One, two, three or more members of the family were affected in 87.2%, 7.8% and 5% of positive relatives in IMID, respectively. The most recurrent diseases were psoriasis (2.69% [95% CI: 2.32-3.06]) and rheumatic arthritis (1.07% [95% CI: 0.70-1.44]). There were differences in prevalence due to sex (p = 0.004) and age (p = 0.000). No significant differences were identified related to geo- graphic location (p = 0.819). Attendance of at least 2 IMID was reported in 8.9% of respondents. Conclusions: The overall prevalence was of the IMID studied was 6.39%, psoriasis being the most frequent with 2.69%. This study constitutes an initial step to consider IMID as an independent disease within the health system..Fundamentos: Las enfermedades inflamatorias inmunomediadas (IMID) son enfermedades crónicas y altamente discapacitantes que comparten secuencias inflamatorias y desregulaciones inmunológicas. Considerada como una enfermedad en sí, la prevalencia de la IMID es prácticamente des- conocida. El objetivo de este trabajo fue valorar la prevalencia de 10 IMID seleccionadas, incluyendo artritis reumatoide, psoriasis, artritis psoriásica, espondilitis anquilosante, colitis ulcerosa, enfermedad de Crohn, lupus erite- matoso sistémico, hidrosadenitis supurativa, sarcoidosis y uveítis en España. Métodos: Se hizo un estudio epidemiológico transversal de prevalencia puntual. Este estudio llevó a cabo a través de una serie de entrevistas informa- tizadas en hogares elegidos al azar en 17 comunidades autónomas en España. Mediante un cuestionario estructurado se determinó la frecuencia de diagnós- tico y las concurrencias de 10 IMID en los encuestados y otros individuos pertenecientes al mismo núcleo familiar. Las estimaciones de prevalencia pun- tual se utilizaron y compararon con el objetivo de determinar la frecuencia de IMID por edad, sexo y comunidades. Los datos fueron procesados utilizando el programa Excel 2016 (Microsoft, Redmond, WA, USA) y el sistema SPSS V.019 (IBM Corp. Armonk, NY, USA) para el análisis estadístico utilizando los test estadísticos habituales en este tipo de estudios. Resultados: : De los 7.980 encuestados, 510 fueron diagnosticados con una IMID, lo que representa un estudio transversal de un 6,39% (95% ci: 6,02-6,76). Uno, dos, tres o más miembros de la familia estaban afectados en un 87,2%, 7,8% y 5% de familiares positivos en IMID, respectivamente. Las enfermedades más recurrentes fueron psoriasis (2,69% [95% ci: 2,32-3,06]) y artritis reumática (1,07% [95% ci:0,70-1,44]). Se observaron diferencias en la prevalencia debidas al sexo (p=0,004) y edad (p=0,000). No se identi- ficaron diferencias significativas relacionadas con la localización geográfica (p=0,819). Se reportó concurrencia de al menos 2 IMID en un 8,9% de en- cuestados. Conclusiones: La prevalencia global fue de las IMID estudiadas fue del 6,39 % siendo las mas frecuentes la psoriasis con el 2,69%. Este estudio cons- tituye un paso inicial para considerar la IMID como una enfermedad indepen- diente dentro del sistema sanitari