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New tumour necrosis factor inhibitors for rheumatoid arthritis: are there benefits from extending choice?
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  1. David L Scott1,
  2. Andrew Cope2
  1. 1
    Academic Department of Rheumatology, King’s College London School of Medicine, Weston Education Centre, King’s College London, London, UK
  2. 2
    Academic Department of Rheumatology, King’s College London School of Medicine, Guy’s Hospital, London, UK
  1. Professor D L Scott, Academic Department of Rheumatology, King’s College London School of Medicine, Weston Education Centre, King’s College London, 10 Cutcombe Road, London SE5 9RS, UK; david.l.scott{at}kcl.ac.uk

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Certolizumab pegol (UCB, Brussels, Belgium) and golimumab (Centocor, Horsham, Pennsylvania, USA) are the latest tumour necrosis factor (TNF) inhibitors evaluated in double-blind, multicentre randomised controlled trials (RCT). Certolizimab is the pegylated (polyethylene glycolated) Fab′ fragment derived from a high affinity humanised anti-TNFα monocolonal antibody (mAb). Fab′ fragments lack the Fc portion of immunoglobulin, and so the repertoire of Fc-mediated effector responses, such as complement or antibody-dependent cell-mediated cytotoxicity, is distinct from those of other anti-TNF mAb. Nonetheless, it still neutralises membrane TNFα. Derivatisation of the Fab′ fragment prolongs the plasma half-life to 2 weeks. Certolizumab pegol is administered by subcutaneous injection (200 or 400 mg) every 2 weeks. Golimumab is a human anti-TNF mAb administered by subcutaneous injections (50 or 100 mg) every 4 weeks. Three RCT in this issue of Annals of the Rheumatic Diseases,13 (see pages 789, 797 and 805) which report their use in active rheumatoid arthritis (RA), raise two questions. First, do we need more TNF inhibitors? Second, how effective and safe are these new TNF inhibitors?

Successful drugs are invariably replicated. “Breakthrough” treatments sound more impressive than subsequent “me too” replications, although the latter products might perform better. Lee4 has elegantly summarised the arguments for “me too” products, indicating that their presence “does not mean that imitation has replaced innovation”. Successful “me too” treatments improve efficacy, reduce toxicity and increase “cost effectiveness”. With biological agents such as TNF inhibitors their added benefits may include more favourable routes or frequencies of administration.

There are cogent reasons to anticipate that “me too” biological agents will be commonplace as experience with these agents solidifies and their use increases. There may be special factors with biologicals, particularly around their mechanism of action, which may complicate the comparison of different “me too” products. …

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