Anti-TNF levels not related to Crohn’s disease recurrence post op

IBD

By Mardi Chapman

9 Feb 2018

Levels of anti-TNF drugs do not predict Crohn’s disease recurrence after surgery, an Australian trial shows.

Adalimumab concentrations did not differ significantly between patients in endoscopic remission post intestinal resection and those who have a recurrence, the multicentre study found.

The finding, from a sub-study of the Post-Operative Crohn’s Endoscopic Recurrence (POCER) study, suggests non-TNF-mediated mechanisms may be important in disease recurrence.

The study of 52 patients across hospitals in Australia and New Zealand found adalimumab concentration was not correlated with endoscopic remission rates at either six or 18 months.

Similarly, adalimumab plasma concentration quartiles were not associated with endoscopic or clinical remission. Endoscopic remission rates were 64% for the lowest adalimumab quartile, 56% for quartile 2, 81% in quartile 3 and 83% in the highest quartile.

“Mechanisms other than inadequate anti-TNF drug concentration are therefore likely to be important,” the study said.

“The same is true of the increased recurrence related to smoking. The mechanistic cause of disease recurrence after surgery requires further research.”

Gastroenterologist Dr Emily Wright, from St Vincent’s Hospital and the University of Melbourne, told the limbic the findings did not mean that therapeutic drug monitoring (TDM) was not still incredibly useful in IBD or that adalimumab was not useful in this setting.

“The particular clinical situation that this paper looks at, being recurrence of Crohn’s disease post operatively, is a very unique and complicated clinical situation and it doesn’t appear that the drug level on its own is enough to predict whether a patient will get recurrence or not.”

“We need more research in TDM generally and in terms of the post operative scenario, we probably need more sophisticated ways of interrogating all sorts of disease factors whether it is serological, genetic or bacterial profiles to see if that can give us more information about why disease comes back in some patients and not others despite having adequate drug levels.”

The study also found the presence of anti-adalimumab antibodies was not associated with a higher risk of endoscopic recurrence.

Antibodies were present in about one quarter of patients and more common in patients on monotherapy versus combination therapy with thiopurine.

While the presence of antibodies was associated with lower drug levels, adalimumab concentrations remained within the therapeutic range in most patients.

Fecal adalimumab levels in all patients were below the level of quantification.

“Most likely this relates to the small disease burden with localised recurrent inflammation,” the study authors said.

“This is a novel finding that this phenomenon of luminal drug loss appears to be something seen in a handful of patients with very severe disease but we didn’t see that at all in this group,” Dr Wright added.

 

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