Hepatitis B Virus Reactivation Potentiated by Biologics

The advantage of the newer biological therapies is that the immunosuppressive effect is targeted, in contrast, to the standard, traditional immunomodulatory agents, which have a more global effect. However, there are unintended targets and consequences, even to these “precise” therapeutics, leading to acquired or secondary immunodeficiencies. Besides depleting specific cellular immune subsets, these biological agents, which include monoclonal antibodies against biologically relevant molecules, often have broader functional immune consequences, which become apparent over time. This review focuses on acquired B-cell immunodeficiency, secondary to the use of B-cell depleting therapeutic agents. Among the many adverse consequences of B-cell depletion is the risk of hypogammaglobulinemia, failure of B-cell recovery, impaired B-cell differentiation, and risk of infections. Factors, which modulate the outcomes of B-cell depleting therapies, include the intrinsic nature of the underlying disease, the concomitant use of other immunomodulatory agents, and the clinical status of the patient and other co-existing morbidities. This article seeks to explore the mechanism of action of B-cell depleting agents, the clinical utility and adverse effects of these therapies, and the relevance of systematic and serial laboratory immune monitoring in identifying patients at risk for developing immunological complications, and who may benefit from early intervention to mitigate the secondary consequences. Though these biological drugs are gaining widespread use, a harmonized approach to immune evaluation pre-and post-treatment has not yet gained traction across multiple clinical specialties, because of which, the true prevalence of these adverse events cannot be determined in the treated population, and a systematic and evidence-based dosing schedule cannot be developed. The aim of this review is to bring these issues into focus, and initiate a multi-specialty, data-driven approach to immune monitoring.

Elaborar recomendaciones para la prevención de infección en pacientes adultos con enfermedades reumáticas autoinmunes sistémicas (ERAS).

Un panel de expertos, seleccionados con base en su currículum y experiencia, identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Se realizaron revisiones sistemáticas de la evidencia, que se graduó de acuerdo con los criterios del Scottish Intercollegiate Guidelines Network. Tras ello, se formularon las recomendaciones.

Se seleccionaron cinco preguntas, referentes a la prevención de infección por Pneumocystis jirovecii con trimetoprim-sulfametoxazol, medidas profilácticas contra el virus de la hepatitis B, vacunación contra el virus del papiloma humano, vacunación contra el Streptococcus pneumoniae y vacunación contra el virus de la gripe. Se formularon un total de 18 recomendaciones, estructuradas por pregunta, con base en la evidencia encontrada para las diferentes ERAS y/o consenso de expertos.

Existe suficiente evidencia sobre la seguridad y eficacia de las vacunaciones y otras medidas profilácticas frente a los microrganismos revisados en este documento como para ser recomendadas específicamente en pacientes con ERAS.

To develop recommendations for the prevention of infection in adult patients with systemic autoimmune rheumatic diseases (SARD).

Clinical research questions relevant to the objective of the document were identified by a panel of experts selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network criteria. Specific recommendations were made.

Five questions were selected, referring to prevention of infection by Pneumocystis jirovecii with trimethoprim/sulfamethoxazole, primary and secondary prophylactic measures against hepatitis B virus, vaccination against human papillomavirus, vaccination against Streptococcus pneumoniae and vaccination against influenza virus, making a total of 18 recommendations, structured by question, based on the evidence found for the different SARD and/or expert consensus.

There is enough evidence on the safety and efficacy of vaccinations and other prophylactic measures against the microorganisms reviewed in this document to specifically recommend them for patients with SARD.

To date, an estimated 300 million people worldwide have been infected with chronic hepatitis B virus (HBV). Although anti-HBV therapies have improved the long-term survival profile of chronic carriers, viral reactivation still poses a significant challenge for preventing HBV-related hepatitis, hepatocellular carcinoma (HCC), and death. Immuno-modulating drugs, which are widely applied in managing rheumatic conditions, are commonly associated with HBV reactivation (HBVr) as a result of drug-induced immune suppression. However, there are few reports on the risk of HBVr and the medication management plan for HBV carriers, especially rheumatic patients. In this review, we summarize immuno-modulating drug-induced HBVr during rheumatoid therapy and its preventive strategies for HBVr-induced liver diseases, especially cirrhosis and HCC. These findings will assist with developing treatments for rheumatic patients, and prevent HBV-related cirrhosis and HCC.

There is a large reservoir of individuals with past hepatitis B virus (HBV) infection that are in risk for HBV reactivation when immunosuppressed. On the setting of hematologic malignancy, the malignancy itself and currently used treatments, especially anti-CD20 agents, have risk of HBV reactivation. Antiviral prophylaxis is recommended by some international societies. We present a case of HBV reactivation more than 12 months after stopping rituximab containing treatment and 6 months of antiviral prophylaxis with entecavir, in a patient with HBV functional cure. The patient was restarted on antivirals and again obtain functional cure. The antiviral was stopped 1 year after seroconversion and the patient followed for another year without evidence of new reactivation. Most literature supports the use of antiviral prophylaxis in patients treated with rituximab. However, there are still conflicting indications and no consensus regarding the duration of prophylaxis. This clinical case and review of the literature supports a longer prophylaxis duration (more than 18 months after finishing rituximab treatments) instead of standard 12 months prophylaxis.