Letter

Etanercept monotherapy for a patient with psoriasis, psoriatic arthritis, and concomitant hepatitis C infection

Despite the availability of several new systemic agents for psoriasis treatment, choosing the right therapy in certain patient populations can be challenging. There are few up-to-date reviews on systemic drugs for moderate to severe psoriasis in pregnant and pediatric patients and in patients with concomitant chronic infections, such as hepatitis, HIV, and latent tuberculosis. These groups are usually excluded from clinical trials, and much of the available evidence is based on anecdotal case reports and case series. As a chronic disease, psoriasis requires long-term treatment, and there are concerns of adverse maternal–fetal outcomes, long-term side effects in children, and the reactivation of latent infections with the use of systemic agents in these patients. The second article in this continuing medical education series provides insights for choosing appropriate systemic agents for treating moderate to severe psoriasis in pregnant and pediatric patients and in the setting of chronic infections, such as hepatitis, HIV, and latent tuberculosis.

Patients with psoriasis on biologic therapies and a history of viral hepatitis carry a risk for reactivation.

We evaluated safety of biologic therapies in psoriasis patients seropositive for hepatitis B or C viruses (HBV, HCV).

A retrospective cohort study design was used. Clinical and laboratory data for 30 patients undergoing biologic therapy who were seropositive for HBV or HCV were evaluated. Next, a systematic review was performed. Primary outcomes were hepatitis and viral reactivation during therapy. Treatment duration and antiviral prophylaxis were also recorded.

Serology indicated HCV infection in 4 patients, past HBV infection in 17 patients, isolated core antibody in 8 patients, and chronic HBV infection in 1 patient. During follow-up (mean 4.85 ± 3.1 years), no patients experienced hepatitis or viral reactivation. The systematic review of the literature included 49 studies comprising 312 patients followed for a mean of 30.9 months. Viral reactivation occurred in 2/175 patients who were seropositive for core antibody and 3/97 with HCV infection (yearly rates, 0.32% and 2.42%, respectively) compared with 8/40 patients with chronic HBV infection (yearly rate, 13.92%). Three of these 8 patients with reactivated HBV infection received antiviral prophylaxis.

We pooled heterogeneous studies evaluating different biologic therapies.

Biologic therapies pose minimal risk for viral reactivation in low-risk patients without hepatitis seropositive for HCV or HBV core antibody but are a considerable risk in patients with chronic HBV infection, highlighting the necessity of antiviral prophylaxis.

The therapy of patients with psoriasis and liver disease can be a challenge due to the increased risk of adverse effects from traditional systemic treatments; in addition, although the anti-tumor necrosis factor agents are considered safer, they have also been associated with drug-induced liver injury and reactivation of viral hepatitis. Ustekinumab has a different mechanism of action and the little that is known of its effects on the liver comes from pivotal studies. The objectives of this study were to estimate the incidence of drug-induced liver injury in patients treated with ustekinumab in daily clinical practice and to analyze liver alterations in those patients with pre-existing liver disease.

All patients treated with the standard regimen of ustekinumab were included in the study. Variables gathered included age, sex, type of psoriasis, nail involvement, arthritis, previous treatments, history of liver disease, viral serology, Psoriasis Area Severity Index (at baseline and at 12, 16, and 52 weeks), transaminase levels, manifestations of liver disease, liver ultrasound, and factors such as body mass index, alcohol consumption, and ferritin levels.

Grade 1 elevation of the transaminases was only observed in 6 patients; no cases of severe hypertransaminasemia were observed. None of the patients with elevation of the transaminases at baseline developed problems during treatment.

Ustekinumab-related liver injury is uncommon and mild. From a hepatic point of view, the drug appears safe, even in patients with pre-existing liver disease and those who have developed altered liver function previously with other drugs.

Los pacientes con psoriasis y hepatopatías son un reto terapéutico dado el mayor riesgo de efectos adversos que presentan con el tratamiento sistémico clásico y a que, aunque los fármacos anti-TNF-α son considerados más seguros, también se han descrito reactivaciones de hepatitis vírica y hepatitis tóxica en relación con los mismos. El ustekinumab (UTK) tiene un mecanismo de acción diferente y se sabe poco de sus efectos en el hígado, sobre todo a partir de los estudios pivotales. Nuestro objetivo ha sido estimar la incidencia de toxicidad hepática en los pacientes tratados con UTK en la práctica clínica habitual, y examinar los cambios hepáticos en aquellos pacientes tratados que tenían hepatopatía de base.

Se incluyeron todos los pacientes tratados con UTK según pauta habitual. Se analizaron la edad, el género, el tipo de psoriasis, la afectación ungueal, la artritis, los tratamientos previos, la hepatopatía previa, las serologías virales y el PASI (basal y a las 12, 16 y 52 semanas). Se analizaron también las transaminasas, los signos y síntomas de hepatopatía y los factores como el índice de masa corporal, el hábito enólico, la ferritina y la ecografía hepática.

Se observaron hipertransaminasemias de grado 1 en solo 6 pacientes. Ninguno presentó hipertransaminasemias graves. Ninguno de los pacientes con hipertransaminasemia basal tuvo problemas durante el tratamiento.

La hepatotoxicidad asociada a UTK es poco frecuente y grave, y parece seguro a nivel hepático, incluso en pacientes con hepatopatía basal o que habían presentado con anterioridad alteraciones hepáticas con otros fármacos.

Tumor necrosis factor–alfa levels are linked to disease severity in patients with inflammatory conditions, such as psoriasis. Inhibitors of this cytokine are commonly used with significant success in the treatment of such inflammatory disorders. Their use, however, can be plagued by infectious complications. An awareness of potential infections associated with these therapies is critical in order to maximize preventive efforts both before and during therapy. This review provides a guide for dermatologists caring for patients in need of this type of biologic therapy to preemptively address the infectious risks. Part II of this continuing medical education article reviews recommended screening methods for patients undergoing evaluations for tumor necrosis factor inhibitor therapy for psoriasis or other dermatologic diseases, and discusses possible prophylactic strategies to use, including the appropriate use of immunizations.

Tanto la psoriasis como las infecciones crónicas por los virus de la hepatitis B (VHB) y C (VHC) tienen una alta prevalencia, por tanto la coincidencia en un mismo paciente es relativamente fácil. Si se trata de una psoriasis que requiere tratamiento sistémico el dermatólogo deberá considerar la comorbilidad hepática a la hora de seleccionar un tratamiento adecuado. Ciclosporina, además de otros efectos adversos bien conocidos, es un agente inmunosupresor que puede condicionar una peor evolución de la hepatitis vírica. Por otra parte, los retinoides, psoralenos y, sobre todo, metotrexato pueden empeorar la función hepática. Los agentes biológicos anti-factor de necrosis tumoral alfa (TNF-α) no son hepatotóxicos, y su teórica contraindicación en este contexto vendría dada por su acción sobre la respuesta inmune y el eventual riesgo de reactivación de la infección hepática. Sin embargo, diversos estudios han demostrado que ni la carga viral ni los parámetros de inflamación hepática suelen modificarse negativamente cuando se utilizan en hepatitis por el VHC. Su uso en este contexto, con una correcta monitorización, parece por tanto muy razonable. En cambio, en la hepatitis crónica por el VHB, sí existen casos de agravamiento, incluso con desenlace fatal en alguna ocasión, y el uso de estos agentes biológicos debe reservarse para casos de mayor necesidad, siempre asociados a tratamiento antiviral y monitorización estricta. La revisión de la literatura reciente parece permitir la conclusión de que el uso concomitante de lamivudina reduciría mucho el riesgo de reactivación viral y, con esta condición, puede también contemplarse el uso de etanercept en ciertos pacientes positivos para el VHB.

Both psoriasis and chronic infections by HBV and HCV have high prevalence. Thus, it is relatively easy for them to coincide in the same patient. If the psoriasis requires systemic treatment, the dermatologist should consider the hepatic comorbidity when selecting an appropriate treatment. Cyclosporine, in addition to other well-known side effects, is an immunosuppressant that may condition worse evolution of the viral hepatitis. On the other hand, retinoids, psoralens and, above all, methotrexate may worsen the liver function. The anti-TNF-α biological agents are not hepatotoxic and their theoretical contraindication in this context would be because of their action on the immune response and risk of reactivation of the hepatic infection. However, several studies have demonstrated that neither the viral load nor the hepatic inflammation parameters are generally modified negatively when they are used in hepatitis due to HCV. Their use in this context, with correct monitoring, seems, therefore, very reasonable. On the contrary, in chronic hepatitis B virus, there are cases of worsening, even with fatal outcome in some cases, and the use of these biological agents should be reserved for cases having greater need, and always be associated to antiviral treatment and strict monitoring. The review of the recent literature seems to allow the conclusion that the concomitant use of lamivudine would greatly reduce the risk of viral reactivation and, with this condition, the use of etanercept in some HBV + patients may also be contemplated.