Vicente Oliver Martínez

Safety of Etanercept in Psoriasis A Critical Review

Conventional systemic treatments for patients with psoriasis are associated with multiple adverse effects that require continuous monitoring. The introduction of new biological agents such as etanercept, a fully human fusion protein, has permitted individualisation of patients’ treatment according to disease stage. The drug is a competitive inhibitor of tumour necrosis factor-α (TNFα) that prevents interaction between this cytokine and its cell surface receptors. Etanercept also modulates the activity of other inflammatory cytokines and does not induce complement-mediated cell lysis in vitro.The main source of information regarding etanercept safety comes from studies in patients with rheumatoid arthritis. The most common adverse effect during drug administration is mild injection site reactions. There is no increase in the overall incidence of infections compared with placebo, although there have been several reports of infections caused by intracellular organisms (Mycobacterium tuberculosis, Listeria monocytogenes, and Mycobacterium avium intracellulare). Therefore, combination of this drug with corticosteroids must be carefully monitored and should be avoided in patients with established sepsis.There are no data showing that treatment with etanercept results in an increase in the occurrence of malignant neoplasms. However, caution is recommended in use of etanercept in patients with a current or past history of demyelinating disease. Etanercept must be used with extreme caution in patients with heart failure because of several reports indicating a worsening or de novo occurrence of congestive heart failure while receiving the drug. Monitoring of autoantibodies is not currently considered necessary as they do not predict response, toxicity or autoimmune events. The presence of non-neutralising antibodies to the TNF receptor fragment or other protein components of etanercept has not been related to a decrease in drug response or adverse reactions. Etanercept does not generally modify the course of inflammatory bowel disease. When combined with other systemic therapies for psoriasis, current data do not show an increase in adverse events.In patients with hepatitis C viral infection, etanercept does not increase transaminase levels or viral load and in some instances has allowed the concomitant use of interferon which had previously been discontinued because of a worsening of psoriasis. Etanercept is rated as a US FDA category B drug in pregnancy. However, its use is not recommended in pregnant women unless the benefit-risk ratio greatly favours its use. Etanercept is not recommended for use in lactating women.Etanercept represents a relevant treatment for psoriasis, efficacious over many weeks and safe but special care should be taken to avoid the potential risks.

Factores pronósticos en el melanoma maligno cutáneo localizado: estudio de 639 pacientes

BACKGROUND AND OBJECTIVE: Several clinical and histological prognostic factors have been identified in localized melanoma. However, further studies with better defined and more reproducible histological parameters are needed. Our aim was to identify the prognostic factors for survival in cutaneous melanoma in the Spanish population. PATIENTS AND METHOD: Six hundred and thirty nine patients with localized melanoma, stages I and II of the last version of the American Joint Committee on Cancer staging system for cutaneous melanoma, with 2 years of follow-up or documented relapse, were selected from the database of the Department of Dermatology. Univariate and multivariate Cox regression analyses were performed for overall and disease free survival. RESULTS: Tumor thickness appeared as the most important prognostic factor for both overall and disease free survival in the multivariate analysis. Inflammatory infiltrate and sex were only significant for overall survival, and location, age and ulceration were significant for disease free survival. Other variables, such as histological type, mitotic rate or level of invasion, lost their prognostic significance in the multivariate analysis. CONCLUSIONS: Tumor thickness is the most important prognostic factor to predict survival in localized melanoma. Other factors such as sex, inflammatory infiltrate, location, age or ulceration, have also an important role in prognosis.

Tratamiento de la psoriasis extensa y refractaria con infliximab

Fundamento y objetivo El objetivo de este estudio fue determinar el numero y la proporcion de pacientes con psoriasis extensa y refractaria que mejoraron tras la administracion de infliximab. Pacientes y metodo Se estudio a pacientes con psoriasis grave refractaria a otros tratamientos sistemicos, a los que se les administro infliximab (5 mg/kg) en las semanas 0, 2, 6, y posteriormente cada 8 semanas. Presentamos los resultados del Psoriasis Assessment and Severity Index (PASI) y de la Body Surface Assessment (BSA) en las semanas 6 y 30. resultados El 90% de los pacientes experimentaron una mejoria en el PASI y la BSA respecto de los basales ya en la semana 6.El 63,6% de ellos alcanzo una mejoria del 75% en el PASI y el 72,7% una mejoria del 50% en la BSA. Esta mejoria se mantuvo hasta la semana 30 en un 54,5 y un 72,7%, respectivamente. El farmaco fue bien tolerado, sin reacciones adversas. conclusiones El infliximab parece una Buena opcion en el tratamiento de pacientes con psoriasis extensa y refractaria a tratamientos habituales.

Efficacy and safety of ustekinumab in a patient with chronic renal failure on hemodialysis

chronic renal failure on hemodialysis Dear Editor, Moderate to severe psoriasis is a chronic immunemediated disorder that may require long-term therapy. Ustekinumab, the most recent biological agent approved for treatment of adult patients with moderate to severe psoriasis, is a fully human monoclonal antibody that binds to the p40 subunit of interleukin (IL)-12 and IL23. Renal impairment is considered to be a relative or absolute contraindication to several drugs and may augment their toxicity. Nevertheless, the literature contains limited information regarding the use of biological drugs in patients with renal failure. We report the use of ustekinumab in a 65-year-old man with severe refractory psoriasis and end-stage renal failure on hemodialysis. A 65-year-old patient had been followed-up with a diagnosis of psoriasis for 27 years. He had also suffered from hypertension, ischemic heart disease, and chronic renal failure four years ago. After failure of other treatments, such as methotrexate, cyclosporine, acitretin, and phototherapy, he was given etanercept 50 mg/week, which did not improve his psoriasis and was stopped after seven months. The patient showed a PASI score (Fig. 1) of 15, so we switched the him to ustekinumab treatment at a standard dose of 45 mg subcutaneously initially and once again four weeks later, followed by 45 mg once every 12 weeks. The patient showed a significant improvement of the PASI score already after four weeks of treatment, and further improvements were observed throughout the treatment (Fig. 2). Subsequently, after reaching a glomerular filtration rate of 13.5 mL/min, hemodialysis was initiated, but we decided to go on with the treatment with ustekinumab. After 17 months of treatment, significant remission has been observed, and no relevant changes in renal function have been noted. Safety data from the studies suggest that ustekinumab is generally safe and well tolerated, but there is no information on the treatment with ustekinumab for patients with end-stage renal failure on hemodialysis. Kauffman et al. evaluated safety, pharmacokinetics, and clinical response of single intravenous (IV) administrations of ustekinumab in an open-label, sequential dose escalation study. Ustekinumab demonstrated linear pharmacokinetics over the dose range evaluated. Dose-proportional increases in maximum serum concentration were observed, and similar elimination rates were seen in all doses. The authors concluded that single IV administrations of ustekinumab were safe and well tolerated, and improvements in clinical response were dose dependent. Similar endpoints were evaluated in another Phase I study conducted by Gottlieb et al. In this study, authors assessed safety, pharmacokinetics, pharmacodynamics, and efficacy of ustekinumab, following a single subcutaneous administration, in subjects with moderate-to-severe plaque psoriasis. Dose-proportional peak concentrations were observed, the half-life was approximately 20 days, and the time to peak concentration for ustekinumab was approximately

Intensification therapy with golimumab: a new treatment strategy for moderate–severe refractory psoriasis

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