About this Research Topic
In this Research Topic, we aim to highlight the advances and address knowledge gaps in the prediction, mechanisms and management of adverse events from B-cell targeted therapies (BCTT) in autoimmune disease. BCTT (e.g. rituximab) were first introduced in 1997 for the treatment of lymphoma. Subsequently, BCTT have become established as an important treatment option for a wide range of autoimmune diseases, particularly autoimmune rheumatic diseases (AIRD), including the management of patients with severe cases. BCTT include B-cell depleting drugs such as rituximab and drugs interfering with B-cell survival factors, such as belimumab. Indeed, the latter is the only new SLE therapy to have received a license from the FDA in the last 60 years. Studies combining BCTT are already in progress, e.g. rituximab and belimumab in the BEATLupus, BLISS-BELIEVE, and CALIBRATE clinical trials.
Initially, certain adverse effects of BCTT, such as hypogammaglobulinaemia, appear to have been underestimated. This may be related to a number of factors, including the short duration and limited number of treatment cycles in early reports. Conversely, progressive multifocal leukoencephalopathy was perhaps over-estimated due to a number of early cases and the severity of this condition. Studying adverse events cannot be approached in isolation. As we treat patients holistically, we recognize the need to study toxicity in the context of efficacy. Profound and prolonged B-cell depletion may achieve clinical remission, but result in sustained hypogammaglobulinaemia in a proportion of patients.
Other important adverse effects include neutropenia, hepatitis B reactivation, allergy/infusion reactions, serum sickness, human anti-chimeric antibody responses and primary or secondary non-response. There is a clinical need to improve the selection of patients being prescribed BCTT based on their likelihood to respond or experience specific adverse events. We need to understand the role of early intervention should these occur. Current monitoring of BCTT remains rudimentary and there are major opportunities to improve immunological monitoring for both efficacy and adverse events. Understanding the mechanisms underlying adverse events may not only assist in their management, but may also enhance our comprehension of the immune response to viruses (e.g. JC virus, hepatitis B) and of B-cell homeostasis.
We welcome contributions from the wide range of autoimmune diseases to include AIRD, neurological (e.g. multiple sclerosis, myasthenia gravis), renal (e.g. membranous nephropathy, focal segmental glomerulosclerosis), and dermatologic (e.g. pemphigus) disease. We also welcome research incorporating the potential consequences of COVID-19 on clinical and immunological responses to BCTT and on the development of BCTT-related adverse events.
In this Research topic focusing on BCTT in autoimmune diseases, we seek Original Research, Review, Mini-Review, Hypothesis and Theory, Clinical Trial and Opinion articles that cover, but are not limited to, the following subjects:
• Approaches to enhance monitoring of BCTT efficacy and toxicity
• Predictive factors for development of adverse events from BCTT
• Mechanisms underlying adverse events relating to BCTT
• Infection risk resulting from BCTT, and infection preventive strategies
• Management of adverse events from BCTT
Dr. Ioannis Parodis receives research funding from Amgen Inc, GlaxoSmithKline and Eli Lilly and Company. All other Topic Editors declare no potential competing interests with relation to this Research Topic.
Keywords: B-Cell, rituximab, belimumab, autoimmunity, hypogammaglobulinaemia, neutropenia, allergy, adverse
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