Rheumatology: The Role of High-dose Intravenous Immunoglobulin
Rheumatology: The Role of High-dose Intravenous Immunoglobulin
For many years, non-steroidal anti-inflammatory agents, steroids and immunosuppressive drugs have been the mainstay of treatment for rheumatological disorders. Over the last few years, the emergence of biologic treatments has dramatically changed the management of numerous rheumatological diseases. However, immunoglobulin treatment has been used for decades and its use has still not been superseded in certain rheumatological diseases. In fact, despite the introduction of newer immunomodulatory drugs, there has been an ever-increasing number of clinical indications for which intravenous immunoglobulin (IVIG) has been tried. Immunoglobulins are plasma proteins secreted by plasma cells, forming a major component of the adaptive immune system. IVIG is a blood product prepared from plasma, each batch prepared from a pool of 10 000–20 000 donations. Multiple purification steps during the manufacturing process aim to eliminate all known transmissible pathogens, but cannot completely exclude the risk from unknown pathogens. It should be noted that there has been the transmission of hepatitis C in one batch of immunoglobulin, reported in 1994, resulting in more than 200 patients in the USA and Europe being affected. Nevertheless, IVIG remains relatively safe compared with other immunosuppressive drugs. Headaches and fatigue are common side effects but fortunately the more severe problems such as aseptic meningitis, venous thromboembolism and acute renal failure remain rare. High-dose immunoglobulin when administered i.v. has immunomodulatory properties. The precise mechanism of action of IVIG is complex and not yet fully understood.
For many years, non-steroidal anti-inflammatory agents, steroids and immunosuppressive drugs have been the mainstay of treatment for rheumatological disorders. Over the last few years, the emergence of biologic treatments has dramatically changed the management of numerous rheumatological diseases. However, immunoglobulin treatment has been used for decades and its use has still not been superseded in certain rheumatological diseases. In fact, despite the introduction of newer immunomodulatory drugs, there has been an ever-increasing number of clinical indications for which intravenous immunoglobulin (IVIG) has been tried.
Immunoglobulins are plasma proteins secreted by plasma cells, forming a major component of the adaptive immune system. IVIG is a blood product prepared from plasma, each batch prepared from a pool of 10 000–20 000 donations. Multiple purification steps during the manufacturing process aim to eliminate all known transmissible pathogens, but cannot completely exclude the risk from unknown pathogens. It should be noted that there has been the transmission of hepatitis C in one batch of immunoglobulin, reported in 1994, resulting in more than 200 patients in the USA and Europe being affected. Nevertheless, IVIG remains relatively safe compared with other immunosuppressive drugs. Headaches and fatigue are common side effects, but fortunately the more severe problems such as aseptic meningitis, venous thromboembolism and acute renal failure remain rare.
High-dose immunoglobulin when administered i.v. has immunomodulatory properties. The precise mechanism of action of IVIG is complex and not yet fully understood. Interaction between the Fc fragment of IgG and the Fcγ receptor on target cells appears to be essential for many anti-inflammatory effects. Recent work has highlighted further the numerous actions involving both the innate and adaptive immune system.
IVIG has been used in various inflammatory disorders, and although benefit has been shown in some conditions such as Kawasaki disease (KD), in most cases evidence has been anecdotal in the form of case reports with few randomized controlled trials (RCTs). Many of these reports discuss small numbers of patients treated with IVIG when standard therapy has failed. Pyne et al. reviewed the literature for the use of IVIG in autoimmune rheumatic diseases in 2002. Although there have been many reports since, evidence from large RCTs has been limited. Use in inflammatory diseases has increased and a recent literature search revealed more than 150 off-label usages of IVIG, which included 6781 patients in clinical trials and 362 patients in case reports. In this review, we discuss the problems of IVIG shortages experienced in recent years and the method of prescribing IVIG in the UK, following the recent introduction of the UK demand management plan. We then discuss the evidence of benefit of IVIG in different rheumatological diseases.
Abstract and Introduction
Abstract
For many years, non-steroidal anti-inflammatory agents, steroids and immunosuppressive drugs have been the mainstay of treatment for rheumatological disorders. Over the last few years, the emergence of biologic treatments has dramatically changed the management of numerous rheumatological diseases. However, immunoglobulin treatment has been used for decades and its use has still not been superseded in certain rheumatological diseases. In fact, despite the introduction of newer immunomodulatory drugs, there has been an ever-increasing number of clinical indications for which intravenous immunoglobulin (IVIG) has been tried. Immunoglobulins are plasma proteins secreted by plasma cells, forming a major component of the adaptive immune system. IVIG is a blood product prepared from plasma, each batch prepared from a pool of 10 000–20 000 donations. Multiple purification steps during the manufacturing process aim to eliminate all known transmissible pathogens, but cannot completely exclude the risk from unknown pathogens. It should be noted that there has been the transmission of hepatitis C in one batch of immunoglobulin, reported in 1994, resulting in more than 200 patients in the USA and Europe being affected. Nevertheless, IVIG remains relatively safe compared with other immunosuppressive drugs. Headaches and fatigue are common side effects but fortunately the more severe problems such as aseptic meningitis, venous thromboembolism and acute renal failure remain rare. High-dose immunoglobulin when administered i.v. has immunomodulatory properties. The precise mechanism of action of IVIG is complex and not yet fully understood.
Introduction
For many years, non-steroidal anti-inflammatory agents, steroids and immunosuppressive drugs have been the mainstay of treatment for rheumatological disorders. Over the last few years, the emergence of biologic treatments has dramatically changed the management of numerous rheumatological diseases. However, immunoglobulin treatment has been used for decades and its use has still not been superseded in certain rheumatological diseases. In fact, despite the introduction of newer immunomodulatory drugs, there has been an ever-increasing number of clinical indications for which intravenous immunoglobulin (IVIG) has been tried.
Immunoglobulins are plasma proteins secreted by plasma cells, forming a major component of the adaptive immune system. IVIG is a blood product prepared from plasma, each batch prepared from a pool of 10 000–20 000 donations. Multiple purification steps during the manufacturing process aim to eliminate all known transmissible pathogens, but cannot completely exclude the risk from unknown pathogens. It should be noted that there has been the transmission of hepatitis C in one batch of immunoglobulin, reported in 1994, resulting in more than 200 patients in the USA and Europe being affected. Nevertheless, IVIG remains relatively safe compared with other immunosuppressive drugs. Headaches and fatigue are common side effects, but fortunately the more severe problems such as aseptic meningitis, venous thromboembolism and acute renal failure remain rare.
High-dose immunoglobulin when administered i.v. has immunomodulatory properties. The precise mechanism of action of IVIG is complex and not yet fully understood. Interaction between the Fc fragment of IgG and the Fcγ receptor on target cells appears to be essential for many anti-inflammatory effects. Recent work has highlighted further the numerous actions involving both the innate and adaptive immune system.
IVIG has been used in various inflammatory disorders, and although benefit has been shown in some conditions such as Kawasaki disease (KD), in most cases evidence has been anecdotal in the form of case reports with few randomized controlled trials (RCTs). Many of these reports discuss small numbers of patients treated with IVIG when standard therapy has failed. Pyne et al. reviewed the literature for the use of IVIG in autoimmune rheumatic diseases in 2002. Although there have been many reports since, evidence from large RCTs has been limited. Use in inflammatory diseases has increased and a recent literature search revealed more than 150 off-label usages of IVIG, which included 6781 patients in clinical trials and 362 patients in case reports. In this review, we discuss the problems of IVIG shortages experienced in recent years and the method of prescribing IVIG in the UK, following the recent introduction of the UK demand management plan. We then discuss the evidence of benefit of IVIG in different rheumatological diseases.
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