, James B. Galloway2 and David L. Scott2
(1)
Molecular and Cellular Biology of Inflammation, King’s College London, London, UK
(2)
Rheumatology, King’s College Hospital, London, UK
Abstract
The biologics used in inflammatory arthritis are genetically engineered proteins derived from human genes. They inhibit specific components of the immune system, which play pivotal roles in driving or inhibiting inflammation in arthritis. Unlike conventional drugs that modify the immune system as a whole, biologics affect specific components of the immune system. Theoretically this targeted approach is both more specific in its effects and causes fewer adverse events. However, in reality the complex interactions of cytokines and the multiplicity of cytokine targets means it is difficult to predict the effectiveness and toxicity of cytokine-based interventions such as biologics. There are currently six different classes of biologics available for the treatment of inflammatory arthritis patients. Each inhibits a different aspect of the immune driven inflammatory pathway. This chapter will provide a broad overview of the available biologics, the current treatment pathways dictating their prescribing in the UK and the health economics issues surrounding their use.
Keywords
BiologicsAnti-TNFRituximabTocilizumabAbataceptSide-EffectsIntroduction
A biologic therapy, simply put, is a treatment that has been derived from a biological process rather than being manufactured chemically. In medical terms, this includes blood products, vaccinations and, more recently, monoclonal antibodies (often called “biologics”).
Historically, long term outcomes in RA were considered not to be modifiable [1]. The introduction of biologic drugs has resulted in a complete shift of the goal posts of therapy. Conventional anti- rheumatic drugs such as DMARDs are small molecules that are designed to bind to and interfere with a target receptor. However, a key challenge with a small molecule agent is a lack of specificity. Methotrexate, for example, targets multiple immune pathways including neutrophils, B cells and T cells. The idea of a ‘magic bullet’ approach to target one specific immune process has long been the goal of drug development in RA.
In the late 1990s Elliot et al. published a phase 2 trial of the compound cA2, a monoclonal antibody later to be named infliximab, targeting tumour necrosis factor (TNF) in patients with RA [2]. Elliot’s study revealed results that were unparalleled in the field, with 2/24 patients in the placebo responding, compared to 19/24 in those treated with 10 mg/kg of the study drug. Infliximab moved into phase three trials producing equally optimistic results [3]. Since the success of the first anti-TNF, multiple other monoclonal antibodies have been licensed for the treatment of RA. There are now numerous anti-TNF agents, as well as monoclonal antibodies targeting interleukins, B cells and T cells.
The biologics used in inflammatory arthritis are genetically engineered proteins derived from human genes. They inhibit specific components of the immune system which play pivotal roles in driving or inhibiting inflammation in arthritis. Unlike conventional drugs, that modify the immune system as a whole, biologics affect specific components of the immune system. Theoretically this targeted approach is both more specific in its effects and causes fewer adverse events. However, in reality the complex interactions of cytokines and the multiplicity of cytokine targets means it is difficult to predict the effectiveness and toxicity of cytokine-based interventions such as biologics. Several strategies have been explored to treat inflammatory diseases with cytokines. These include neutralizing cytokines using soluble receptors or monoclonal antibodies, receptor blockade, and the activation of anti-inflammatory pathways by bioengineered versions of immunoregulatory cytokines.
There are currently six different classes of biologics available for the treatment of inflammatory arthritis (Table 7.1). Each inhibits a different aspect of the immune driven inflammatory pathway. These biologic classes comprise:
Table 7.1
Currently available biologic agents for the treatment of inflammatory arthritis
Biologic type | Therapeutic agent(s) | Target disease(s) |
|---|---|---|
TNF-inhibitors | Adalimumab | RA/AS/PsA |
Etanercept | RA/AS/PsA | |
Infliximab | RA/PsAa | |
Certolizumab | RA/ASa/PsAa
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