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* = Presenting author

P073 TNF-alpha activity in plasma from patients with inflammatory bowel disease under adalimumab and infliximab treatment evaluated in a cell-based assay

P. M. Linares*1, H. De la Fuente2, M. Chaparro1, I. Guerra3, P. L. Majano4, M. Iborra5, J. L. Cabriada6, L. Bujanda7, M. Barreiro-de Acosta8, V. García-Sánchez9, I. Marín-Jiménez10, D. Bernardo1, 
J. P. Gisbert1

1Hospital Universitario de La Princesa, IIS-IP and CIBERehd, Gastroenterology Unit, Madrid, Spain, 2Hospital Universitario de La Princesa, IIS-IP, Immunology Unit, Madrid, Spain, 3Hospital Universitario de Fuenlabrada, Gastroenterology Unit, Madrid, Spain, 4Hospital Universitario de La Princesa, IIS-IP and CIBERehd, Molecular Biology Unit, Madrid, Spain, 5Hospital Universitario La Fe and CIBERehd, Gastroenterology Unit, Valencia, Spain, 6Hospital Galdakao, Gastroenterology Unit, Vizcaya, Spain, 7Hospital de Donostia, Instituto Biodonostia, UPV/EHU and CIBEREHD, Gastroenterology Unit, Guipuzcoa, Spain, 8Hospital Clínico Universitario de Santiago, Gastroenterology Unit, Santiago de Compostela, Spain, 9Hospital Universitario Reina Sofía, Gastroenterology Unit, Córdoba, Spain, 10Hospital Gregorio Marañón and IiSGM, Gastroenterology Unit, Madrid, Spain

Background

L929 murine fibroblast is a TNF-alpha sensitive cell line. The usefulness of co-culturing those cells with plasma to assess its in-vitro activity from patients with Crohn’s disease (CD) before and during the induction doses of anti-TNF-alpha drug has not been studied so far. Aims: 1) To evaluate the correlation between TNF-alpha plasma in-vitro activity and clinical activity in CD patients; 2) To assess the usefulness of measuring TNF-alpha plasma in-vitro activity to predict short-term remission with anti-TNF-alpha treatment.

Methods

CD patients naïve to anti-TNF-alpha treatment were prospectively included in this multicentre study. Patients received 160/80 mg adalimumab at weeks 0 and 2, and 40 mg every-other-week thereafter, or infliximab 5 mg/kg at weeks 0, 2, 6 and every-2-months thereafter. Remission was defined as a CDAI score < 150, and response as a decrease of >70 points, after 14 weeks of treatment. Clinical evaluation was assessed, and blood samples were obtained at baseline and at weeks 4 and 14. Receiver operating characteristic (ROC) curves were constructed and the area under the ROC curves (AUCs) were calculated. TNF-alpha-sensitive, actinomycin D–treated murine L929 fibroblasts were employed to quantify TNF-alpha activity in heat-inactivated plasma samples from patients with CD. Human recombinant TNF-alpha was used as a positive control to standardise our assay in a dose-response model.

Results

In the study, 20 patients with active disease at baseline were included (65% received infliximab and 35% adalimumab). Mean TNF-alpha plasma levels were 9.6, 10, and 22.6 pg/mL at baseline, week 4 and 14, respectively. There was no correlation between CDAI score and TNF-alpha activity in any visit. TNF-alpha activity was similar between responders and non-responders at all the visits. There were no differences in TNF-alpha plasma activity between patients that reached remission and those who did not under either anti-TNF-alpha treatment. The AUCs of TNF-alpha activity to predict remission at week 14 were 0.54, 0.50, and 0.58 at baseline and week 4 and 14, respectively.

Conclusion

There was no association between TNF-alpha plasma in-vitro activity at weeks 0, 4, or 14 and clinical response or remission after the induction phase with TNF-alpha in CD patients. TNF-alpha plasma in-vitro activity does not seem useful either to predict or to monitor anti-TNF-alpha treatment during the induction phase in CD patients. Therefore, although TNF has been suggested to have a major role in CD patients, other mechanisms might be involved in this disease. Finally, TNF serum activity is not useful to identify the best candidates for anti-TNF treatment.