1103 Predictive Value of C-Reactive Protein Level Changes On the Long Term Outcome of Infliximab in Crohn's Disease

Abstract

Background & Aims: Infliximab the chimeric monoclonal antibody to TNFα is approved for treatment of moderate to severe Crohn's disease (CD) with 60-70% of patients reporting a clinical benefit both short and long term. We previously showed that loss of response necessitating dose increase and/or interval reduction is observed in 50% of patients over time, and in ±20% this will lead to treatment discontinuation. Non-invasive markers may help to assess therapy outcome and/or need for treatment adjustment if proven accurate. C-reactive protein (CRP) is a reliable marker of inflammation in Crohn's disease. As nothing is known about the effects of CRP on long term outcome to IFX we analyzed the kinetics of CRP over time in a large referral cohort of CD patients treated with IFX. Methods & patients: Serial CRP levels were studied in 547 CD patients with initial response to and treated long term with IFX (median follow up 4.9yrs). CRP was measured before each IFX infusion and was correlated to long term clinical outcome and to need for dose increase and/or interval decrease (SPSS 15.0). A total of 7520 CRP values were available for analyses. Treatment adjustment was defined as successful, if patients continued therapy with IFX without need for other therapies or surgery. Results: Of the total cohort, 273 patients (50.0%) showed sustained clinical benefit of therapy with IFX without need for dose adaptation, whereas 274 (50.0%) patients needed treatment adjustment for loss of response over time. There was no statistical difference between both groups in CRP before start of IFX, CRP measured after first IFX, nor the drop in CRP between both time points. In the 274 patients who needed therapy adjustment, the median CRP just before the adjustment was significantly increased (median 8.5mg/L; IQR 3.1-24.1) as compared to the CRP measured at week 4 (median 3.7mg/L; 1.5-10.5) (p<0.001) but did not reach the pre-treatment levels (18.3mg/ L; IQR 6.4-36.2; p=0.004). In 127 (46.4%) patients, therapy adjustment was successful but in 153 (53.6%) patients, response could not be regained and was followed by discontinuation of IFX. The delta between CRP before and after therapy adjustment was not predictive of success of the treatment interventions (median 1.9mg/L; IQR -0.1-12.5 in the successful adjustments versus 2.2mg/L, IQR 0-14.4 in the non-successful interventions respectively (p= 0.66). Conclusion: CRP is a good non-invasive marker to follow up in patients with CD under IFX and may predict loss of response necessitating therapy adjustment. However, the change in CRP after dose increase did not predict the clinical outcome of dose adjustment in our cohort of patients.