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P183 Loss of anti-tumour necrosis factor (TNF) drugs into faeces and its impact on anti-TNF serum levels and clinical response in Crohn’s disease patients

M. Chaparro*1, I. Guerra2, L. Bujanda3, J. L. Cabriada4, C. Taxonera5, I. Marín-Jiménez6, P. M. Linares1, M. Ramas1, J. P. Gisbert1

1Hospital Universitario de La Princesa, IIS-IP and CIBERehd, Gastroenterology Unit, Madrid, Spain, 2Hospital Universitario de Fuenlabrada, Gastroenterology Unit, Madrid, Spain, 3Hospital de Donostia, Instituto Biodonostia, UPV/EHU and CIBEREHD, Gastroenterology Unit, Guipuzcoa, Spain, 4Hospital Galdakao, Gastroenterology Unit, Vizcaya, Spain, 5Hospital Clínico Universitario San Carlos and IdISSC, Gastroenterology Unit, Madrid, Spain, 6Hospital Gregorio Marañón and IiSGM, Gastroenterology Unit, Madrid, Spain

Background

Intestinal loss of therapeutic anti-TNF drugs was associated with treatment failure in patients with ulcerative colitis. Whether the loss of anti-TNF by the faeces in Crohn’s disease (CD) patients could also be responsible for under-therapeutic drug serum levels, and whether that fact could affect the efficacy of the drug remains completely unknown.

Aims: to assess whether anti-TNF drugs are lost into faeces in CD patients, to know if the loss of anti-TNF drugs into faeces is associated with the lack of response to anti-TNF treatment in CD patients, and to evaluate the correlation between anti-TNF serum and faecal levels.

Methods

CD patients naïve to anti-TNF treatment were prospectively included in a multicentre study. Patients received 160/80 mg adalimumab (ADA) at week 0 and 2, and 40 mg every other week thereafter, or infliximab (IFX) 5 mg/kg at weeks 0, 2, and 6, and every 2 months thereafter. Remission was defined as Harvey–Bradshaw index (HBI) score ≤ 4, and response as a decrease of at least 3 points, after 14 weeks of treatment. Only patients with active luminal CD at baseline were considered for the present study. Clinical evaluation was assessed and blood and faecal samples were obtained at baseline and at weeks 4 and 14. Anti-TNF serum and faecal levels were measured at baseline and at weeks 4 and 14 by Sanquin Biologicals Laboratory (Amsterdam, The Netherlands).

Results

Included were 13 patients (8 received IFX and 5 ADA). Eight patients (61%) were under concomitant immunosuppressants at baseline (6 thiopurines and 2 methotrexate). The median HBI score at baseline was 7 (range 5–16). Moreover, 5 patients were non-responders at week 4 (4 from the IFX and 1 from the ADA group). At week 14, 5 patients (38.5%) were in remission, and 5 patients (38.5%) were non-responders. Anti-TNF drugs were not detected in any blood or faecal samples at baseline. There was a correlation between IFX concentration in faeces and clinical activity at week 4 (correlation coefficient = 0.71, p = 0.04). There was also an inverse correlation between IFX levels and IFX faecal concentration at week 4 (correlation coefficient = -0.74, p = 0.05). With respect to ADA, there was a tendency towards a correlation between ADA concentration in faeces and clinical activity at week 4 (correlation coefficient = 0.81, p = 0.09).

Conclusion

Anti-TNF drugs can be detected in faeces of CD patients under these treatments. There seems to be a negative correlation between anti-TNF levels in serum and in faeces. The more severe the clinical activity, the higher the anti-TNF concentration is detected in faeces.