Introduction: The cytokines interleukin (IL)-12 and IL-23 have been involved in the pathogenesis of psoriasis and psoriatic arthritis. Ustekinumab is a fully human monoclonal antibody targeting the p40 subunit shared by IL-12 and IL-23. Ustekinumab prevents the interaction of IL-12 and IL-23 binding to their receptors, blocking the T1 and T17 inflammatory pathways. Ustekinumab has been evaluated for the treatment of various chronic immune mediated diseases including psoriasis and psoriatic arthritis (PsA). Most of the data regarding the safety of ustekinumab come from the experience treating patients with psoriasis, but clinical trials have demonstrated its efficacy and safety in the treatment of both diseases. The most common adverse events observed during the clinical trials are mild in intensity, and include respiratory tract infections, nasopharyngitis, headache and injection site reactions. Throughout long-term ustekinumab treatment, serious infections or major cardiovascular adverse events occurred rarely. Areas covered: In this review we report the safety data that come from phase II and phase III clinical trials that assay the efficacy and safety of ustekinumab in PsA, including recently published data corresponding to long-term studies. Relevant references were obtained through a literature search in MEDLINE/Pubmed (search strategy: ustekinumab AND psoriatic arthritis) for articles published until November 2016, complemented by a manual search. Expert opinion: In clinical practice, ustekinumab is generally a well-tolerated treatment, and the safety profile in psoriatic arthritis is similar to that reported in plaque psoriasis.
Lewis antigens are terminal fucosylated oligosaccharides synthesized by the sequential action of several glycosyltransferases. The fucosyltransferases are the enzymes responsible for the addition of terminal fucose to precursor oligosaccharides attached to proteins or lipids. These oligosaccharides, defined as cell surface markers, have been implicated in different types of intercellular interactions and in adhesion and invasion processes. Transfection of HT‐29/M3 colon cancer cells with the full length of human fucosyltransferase (FUT1), induces the synthesis of H type 2 and Lewis y antigens, associated with a decrease of sialyl‐Lewis x. The capacity to develop primary tumors when cells were injected intrasplenically was similar in parental and FUT1‐transfected cells, but the capacity to colonize the liver after spleen removal was significantly reduced in M3/FUT1 transfected cells. These results indicate that the expression of FUT1 induces changes in the metastatic capacity of HT‐29/M3 colon cancer cells, as a consequence of the altered expression pattern of type 2 Lewis antigens. Also, an association between MUC5AC expression and the degree of gland differentiation in both primary splenic tumors and hepatic metastases was detected. (Cancer Sci 2007; 98: 1000–1005)
Background Data on the effectiveness and safety of a drug in real-world clinical practice complement the evidence from clinical trials, which are carried out in a different setting. Little has been published on the effectiveness and safety of guselkumab in the treatment of psoriasis in clinical practice. Objectives To assess the effectiveness and safety of guselkumab at 24 weeks in patients with moderate to severe plaque psoriasis in routine clinical practice. Methods Retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis treated with guselkumab for at least 24 weeks in Spain. Results We studied 343 patients, 249 of whom were followed for 24 weeks. By week 24, the mean (SD) Psoriasis Area and Severity Index (PASI) had decreased from 11.1 (7.3) to 1.7 (2.8) (-9.3; [-10.2;-8.4]), 85.9% of the patients had achieved PASI score of 4 or less and 77.9% a PASI score of 2 or less. In terms of relative PASI response, 59.4% of the patients achieved a PASI-90 response and 49.0% a PASI-100 response. On multivariate analysis, 2 factors reduced the probability of a PASI of 2 or less at 24 weeks: a BMI ≥30 (OR, 0.44; 95% CI, 0.22-0.88) and a greater previous exposure to biologic therapy (OR, 0.69; 95% CI, 0.56-0.84]). Adverse events were rare (9.9%) and led to withdrawal from treatment in only 9 patients (2.6%) by the end of the follow-up period. Conclusion The results of this study confirm the high efficacy and safety of guselkumab indicated by the clinical trial data. In clinical practice, the absolute PASI score appears to be a better marker of response to treatment than the relative value.
La artritis psoriásica (APs) es una forma común de artritis inflamatoria que aparece hasta en el 40% de los pacientes con psoriasis. Dado que la afectación cutánea suele preceder a la afectación articular, los dermatólogos desempeñan un papel fundamental en la detección precoz de la APs. El diagnóstico precoz es importante para reducir el riesgo de daños estructurales irreversibles, limitar el deterioro de la función física y mejorar la calidad de vida de los pacientes. El presente documento ha sido elaborado por un grupo de especialistas (nueve dermatólogos y un reumatólogo) con el objetivo de proporcionar recomendaciones sencillas que ayuden a los dermatólogos en el cribado de la APs en pacientes con psoriasis. Los expertos elaboraron el presente documento ofreciendo unas recomendaciones consensuadas basadas en una revisión descriptiva de la evidencia científica disponible y en la experiencia adquirida en la práctica clínica diaria.