Anti-TNF therapy for IBD

In the same issue as the vedolizumab phase 3 studies, there is a succinct review of tumor necrosis antagonist therapy (anti-TNF) therapy for IBD (NEJM 2103; 369: 754-62).

Useful points about IBD:

  • Prevalence of ulcerative colitis (UC) and Crohn’s disease (CD) in North America: 780,000 and 630,00 respectively
  • In first 10 years of CD, cumulative rate of surgery is 40-55%.
  • In first 20 years of UC, rate of colectomy is ~15%.
  • “Recent meta-analysis do not indicate that this drug (mesalamine) has any clinically relevant efficacy in patients with” Crohn’s disease.

Anti-TNF agents:

  • Agents for IBD include infliximab, adalimumab, certolizumab pegol, and golimumab.
  • No head-to-head comparisons have been studied, though the “clinical trials suggest similar efficacy among the available drugs.”
  • Newest approved anti-TNF is golimumab which is administered subcutaneously at a dose of 200 mg at week 0, followed by 100 mg at week 2 and then 100 mg every 4 weeks.
  • A “considerable number of patients with Crohn’s disease (10-40%, depending on selection criteria) do not have a clinically relevant response to currently available TNF inhibitors (primary treatment failure) and among patients with ulcerative colitis, this proportion may be as high as 50%.”
  • “In addition, only about one third to one half of patients with Crohn’s disease have a complete remission, and about two thirds of patients do not have a response that is sustained during 12 months of continuous treatment (secondary treatment failure).”  Many of these patients will respond to dose escalation.
  • The “annual projected cost of each biologic agent for a 70-kg patient with inflammatory bowel disease is approximately $19,000 in the first year and $15,000 in subsequent years.”  These figures exclude the costs associated with administration and dose escalation.

Areas of uncertainty according to the authors:

  • “The value of concomitant treatment with immunosuppressive agents and TNF inhibitors has been debated intensely.”  Combination therapy results in superior efficacy and lower rates of antibodies to anti-TNF agents.  However, “the benefit of combined treatment for more than 12 months is uncertain.”
  • “There are no data to confirm that it (top-down treatment) is actually superior to conventional step-up therapy in terms of disease progression”

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