Indications for IVIG in Rheumatic Diseases
Indications for IVIG in Rheumatic Diseases
The use of IVIG to treat a wide variety of immune-driven diseases has grown rapidly, although the mechanism of action is not completely understood. Increasing demand for IVIG coupled with concerns regarding potential transmissible agents has led to worldwide supply shortages. National agencies have therefore produced guidelines for its use, with the latest England and Wales guideline being published in 2011. Due to the rarity of the rheumatic diseases, the evidence for IVIG use has been shown to be lacking in some areas and promising in others. Conditions in which IVIG has been shown to have benefit include ITP, Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy occurring in the context of rheumatic disease, as well as in SLE, idiopathic inflammatory myopathies and ANCA-associated vasculitides. This review looks at current IVIG use and is designed to be an aid for rheumatologists when considering the use of IVIG in clinical practice.
IVIG is a blood product prepared from the serum of a large number of donors. In recent years, its use has rapidly grown to treat a wide variety of immune-driven diseases. Although the mechanism of action is not completely understood, it is thought that IVIG is mediated via four pathways, including the actions of its many variable regions, known collectively as the antigen-binding fragments (Fab); the actions of its constant fragment (Fc) on host Fc receptors, which are widespread throughout the host immune system; the effects of host complement binding to the Fc fragment of IVIG, causing inhibition of the complement cascade; and other immunomodulatory agents that may be present in IVIG, such as cytokines, cytokine receptors and MHC molecules.
Increasing demand for IVIG coupled with concerns regarding potential transmissible agents has led to recent supply shortages. In the USA, the American Academy of Allergy, Asthma and Immunology first attempted to rationalize its use by publishing a comprehensive list of indications with supporting evidence. Concerning rheumatology, the authors reviewed the evidence for RA, SLE, APS and systemic vasculitis, although they did not offer any clear guidance for the use of IVIG in these diagnoses. Similar guidance has also been published by Canada, Australia and other industrialized countries. The UK Department of Health set up the National Demand Management Programme (NDMP), which first published guidelines for IVIG use in England and Wales in 2008 with a revision in 2011. The NDMP requires each trust to set up an IVIG panel to approve the use of IVIG, depending on the priority given to each diagnosis, with red indications having the highest priority and blue indications as the next priority level. Grey indications have lower priority and indicate those conditions where evidence for IVIG use is lacking and therefore use is only considered and supported in exceptional circumstances and on a case-by-case basis (Table 1).
The aim of this review is to evaluate the current evidence for use of IVIG in rheumatological diseases with particular focus on blue and grey indications, as it is these indications for which rheumatologists will need to provide more justification for its use.
Abstract and Introduction
Abstract
The use of IVIG to treat a wide variety of immune-driven diseases has grown rapidly, although the mechanism of action is not completely understood. Increasing demand for IVIG coupled with concerns regarding potential transmissible agents has led to worldwide supply shortages. National agencies have therefore produced guidelines for its use, with the latest England and Wales guideline being published in 2011. Due to the rarity of the rheumatic diseases, the evidence for IVIG use has been shown to be lacking in some areas and promising in others. Conditions in which IVIG has been shown to have benefit include ITP, Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy occurring in the context of rheumatic disease, as well as in SLE, idiopathic inflammatory myopathies and ANCA-associated vasculitides. This review looks at current IVIG use and is designed to be an aid for rheumatologists when considering the use of IVIG in clinical practice.
Introduction
IVIG is a blood product prepared from the serum of a large number of donors. In recent years, its use has rapidly grown to treat a wide variety of immune-driven diseases. Although the mechanism of action is not completely understood, it is thought that IVIG is mediated via four pathways, including the actions of its many variable regions, known collectively as the antigen-binding fragments (Fab); the actions of its constant fragment (Fc) on host Fc receptors, which are widespread throughout the host immune system; the effects of host complement binding to the Fc fragment of IVIG, causing inhibition of the complement cascade; and other immunomodulatory agents that may be present in IVIG, such as cytokines, cytokine receptors and MHC molecules.
Increasing demand for IVIG coupled with concerns regarding potential transmissible agents has led to recent supply shortages. In the USA, the American Academy of Allergy, Asthma and Immunology first attempted to rationalize its use by publishing a comprehensive list of indications with supporting evidence. Concerning rheumatology, the authors reviewed the evidence for RA, SLE, APS and systemic vasculitis, although they did not offer any clear guidance for the use of IVIG in these diagnoses. Similar guidance has also been published by Canada, Australia and other industrialized countries. The UK Department of Health set up the National Demand Management Programme (NDMP), which first published guidelines for IVIG use in England and Wales in 2008 with a revision in 2011. The NDMP requires each trust to set up an IVIG panel to approve the use of IVIG, depending on the priority given to each diagnosis, with red indications having the highest priority and blue indications as the next priority level. Grey indications have lower priority and indicate those conditions where evidence for IVIG use is lacking and therefore use is only considered and supported in exceptional circumstances and on a case-by-case basis (Table 1).
The aim of this review is to evaluate the current evidence for use of IVIG in rheumatological diseases with particular focus on blue and grey indications, as it is these indications for which rheumatologists will need to provide more justification for its use.
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