An overview of a presentation by Professor Geert D’Haens from Academic Medical Centre, Netherlands, at the Raising Expectations in Gastroenterology symposium, 2012.

Loss of response or no response to anti-TNF therapy can be a primary or secondary phenomenon.

Primary non-response

Primary non-response can be the result of treatment in the absence of an appropriate indication. Patients that may have primary non-response to anti-TNF include:

  • Patients without IBD – other conditions may be contributing to the patient’s symptoms (e.g. infection, abscess or stenosis)
  • Patients with IBD without active inflammation – the more inflammation present at induction, the greater the likelihood of successful anti-TNF therapy1

There are five criteria that should be met before a judgement about primary non-response can be made:

  • Treatment given for a sufficient time
  • Treatment given at a sufficient dose
  • No biological response (e.g. changes in C-reactive protein or faecal calprotectin)
  • No clinical response
  • No endoscopic improvement

Secondary non-response

Secondary non-response can occur after an initial beneficial response to anti-TNF therapy. It can result from the development of complications, such as stenosis, that necessitate treatment cessation, or from pharmacokinetic issues such as antibodies against the medication or low serum levels that reduce efficacy.

There is scope to individualise therapy to address secondary non-response. In a review of 614 patients with Crohn's disease treated with infliximab in clinical practice, "interventions" used to maintain response included:2

  • Reducing the interval between infusions
  • Increasing the dose of infliximab
  • Shifting from episodic treatment to scheduled 8-weekly treatment

Measurement of infliximab trough levels and anti-infliximab antibodies can assist in individualising therapy. For example, low trough levels in the absence of antibodies suggest that dose intensification might be effective. If trough levels are high but antibodies are present, it may be beneficial to switch to another agent with the same mechanism of action. If there is still no response to treatment, it may be necessary to switch to an agent with a different mechanism of action.

Summary

  • Loss of response or no response to anti-TNF therapy can be a primary or secondary phenomenon
  • Repeated evaluation of patients on biologic therapy can assist in individualising therapy
  • Dose intensification or alternative therapies may be required in some patients with secondary non-response

Please note, the views expressed in this article are not necessarily those of the sponsor.

References

  1. Colombel JF et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. New England Journal of Medicine 2010; 362: 1383–1395.
  2. Schnitzler F et al. Long-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a single-centre cohort. Gut 2009; 58: 492–500.

PBS information: This product is listed as a Section 100 item for Crohn’s disease and ulcerative colitis. Refer to PBS Schedule for full authority information.

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