8Anti-TNF therapy
Section snippets
Anti-TNF agents
There are now five TNF inhibitors available for the treatment of RA, three of which are full-length monoclonal antibodies: infliximab, adalimumab and golimumab (Fig. 1 and Table 1). Infliximab is a chimeric protein composed of a murine variable region and human constant region. Golimumab and adalimumab are fully human antibodies, produced using recombinant DNA technology. The fourth agent, etanercept, is a fusion protein of two TNFR2 receptor extracellular domains and the Fc fragment (hinge,
Clinical differences between the anti-TNF agents – do we need five anti-TNFs?
The clinical trial data primarily assessed short-term drug efficacy, protection from radiographic damage and side-effect profiles. In those studies the different drugs appear to be very similar, but a few differences have emerged subsequently, both through studies to optimise treatment efficacy, registries and clinical experience.
Immunogenicity
The clinical significance of the development of anti-drug antibodies (antiglobulins) has yet to be fully understood but these can potentially influence drug efficacy, pharmacokinetics and adverse event profiles. Antiglobulins can form complexes with the target drug resulting in its inactivation or accelerated clearance, which clinically manifests as a requirement for increased drug dosages or a secondary loss of effect. Work in this area has been hampered by the lack of standardised methods for
Switching between anti-TNF agents
Registry data demonstrate that up to 50% of patients will have discontinued a previously effective anti-TNF after 3–4 years, either secondary to adverse effects or lack of efficacy *[26], *[27], [54]. The two options available for these patients are to switch to an alternative anti-TNF or to commence a biologic agent aimed at a different target. The initial encouraging reports for switching to a second anti-TNF came from small studies and case series [55], [56]. There are currently no
Tapering anti-TNF
The efficacy of anti-TNFs is established but the ultimate goal for patients is to gain a drug-free remission which could theoretically reduce potential drug side effects, improve quality of life and reduce overall costs. Although the numbers are small, work in early RA has shown that in some patients it is possible to induce early disease remission with an anti-TNF and later successfully withdraw this treatment *[65], [66]. However, in clinical practice anti-TNFs are most often used in those
Adverse events
Anti-TNF agents have greatly improved the quality of life for many RA patients but there remain concerns regarding the risk of serious adverse events, in particular serious infections and lymphoma. Patients with active RA are already at increased risk of serious complications and the question is whether these agents increase the risk above that of a similar but non-biologically treated RA population. The anti-TNF agents have now been licenced for over 10 years and our understanding of their
Personalised medicine
The ideal for both patients and clinicians would be to optimise and personalise medical care, thereby improving the risk:benefit ratio of the medications prescribed whilst simultaneously reducing costs. We know that approximately one-third of patients will not have a satisfactory response to their first anti-TNF therapy and others encounter side effects. In the coming years, we may come to use demographics, clinical characteristics and probably biomarkers to target the most appropriate agent to
Summary
Five different anti-TNF agents are now available for clinical use, and biosimilar drugs are on the horizon. Although some of these can be used as monotherapy according to their licence, all appear more effective when combined with MTX. Registries suggest that patients remain on etanercept for the longest and infliximab for the shortest time but, in the absence of head-to-head studies it is difficult to make definitive comparisons. However, these data are consistent with immunogenicity studies
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