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Risk of lymphoma in patients with RA treated with anti-TNFα agents
  1. J P Franklin,
  2. D P M Symmons,
  3. A J Silman
  1. ARC Epidemiology Unit, Manchester University Medical School, Manchester M13 9PT, UK
  1. Correspondence to:
    Professor A J Silman
    a.silmanmanchester.ac.uk

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Does anti-TNFα treatment increase lymphoma risk independently of disease severity?

Tumour necrosis factor (TNF)α, is a proinflammatory cytokine central to the pathogenesis of rheumatoid arthritis (RA). Drugs that block the action of this cytokine have been shown to be effective in reducing inflammation and slowing disease progression in patients with RA.1,2 TNFα also provides an essential immune function by promoting a cytotoxic response from T cells against B cell lymphomas.3,4 This raises a theoretical concern that agents blocking TNFα may contribute to an increased risk of such lymphomas, emphasising the need for long term safety surveillance of these drugs. These phenomena need to be considered against the background that the occurrence of lymphoma in patients with RA might be associated with disease activity or severity. If this were so, given the effectiveness of anti-TNFα agents, it is possible that their use may actually reduce lymphoma risk, or at least counteract any possible increase.

There is good evidence that the risk of lymphoma is related to RA severity. Baecklund and colleagues showed, using a nested case-control study of patients with RA with lymphoma, that inflammatory activity was strongly associated with the risk of developing lymphoma. This association persisted even after adjusting for differences in treatment exposure between groups.5 Overall, those patients classified as having “high inflammatory activity” were 25 times more likely to be diagnosed with lymphoma than those with “low inflammatory activity”. Wolfe published similar data showing a relationship between a high erythrocyte sedimentation rate and the risk of lymphoma.6 Thus, any interpretation of …

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