Z Gastroenterol 2008; 46 - A15
DOI: 10.1055/s-2008-1081522

Subclinical inflammation, disease relapse and reresponse upon dose increase: An ACCENT I subanalysis

W Reinisch 1, G Lang 2, A Fasanmade 2, A Olson 2, D Esser 3
  • 1AKH Wien, Austria
  • 2Centocor R & D, Malvern, PA, United States
  • 3Centocor B.V., Leiden, The Netherlands

Introduction: We investigated whether ACCENT I patients clinically responding to scheduled infliximab therapy were more likely to experience a future disease relapse if they showed signs of persistent subclinical inflammation, using Creactive protein (CRP) as a marker. We further investigated if response was reestablished upon crossover to a higher dose.

Aims & Methods: In ACCENT I, 573 patients with active CD received an infusion of 5mg/kg infliximab and were randomised into an episodic (Group 1) and two infliximab scheduled treatment groups. The scheduled treatment groups received further infusions of 5mg/kg infliximab at weeks 2 and 6 followed by 8-weekly infusions of 5mg/kg (Group 2) or 10mg/kg (Group 3). Patients who lost response after week 14 could cross over to treatment upon flare with 10mg/kg (Group 2) or 15mg/kg (Group 3) infliximab. We conducted a retrospective analysis of patients in Groups 2 and 3 (scheduled infliximab treatment) who responded at weeks 2 and 14, i.e. after an initial dose and a full induction regimen. Disease relapse at any timepoint after week 14 was analysed according to CRP status at week 14 (high, >=0.8mg/dL; low, <0.8mg/dL).

Results: 157 patients randomised to scheduled infliximab treatment were in response at weeks 2 and 14. Patients with high CRP levels at week 14 were more likely to experience a future disease relapse than those with low levels (Group 2: 63% (10/16) vs. 49% (31/63); Group 3: 54% (15/28) vs. 24% (12/50); Overall: 57% (25/44) vs. 38% (43/113); p=0.0097 using a Cochran-Mantel-Haenszel test stratified by treatment group). Of the 25 patients with elevated CRP and future disease relapse; 10 opted for crossover to an increased dose of infliximab. 8 of these patients reresponded continuously thereafter, and 2 re-responded partially.

Conclusion: In ACCENT I patients clinically responding to scheduled infliximab therapy, an elevated CRP level indicative of subclinical inflammation was predictive of a future disease relapse. Response was re-established partially or completely in all those patients subsequently crossing over to a higher dose of infliximab. It is possible that more frequent relapse in these patients was driven by more rapid drug clearance, higher disease activity, or both. Further research is needed to investigate any causal relationship between these factors.