Dr Susanna Nikolaus and colleagues from Kiel, Germany, assessed the clinical and immunological mechanisms of failure to respond to infliximab.
A group of 24 patients with steroid refractory, chronic active Crohn's disease (Crohn's disease activity index [CDAI] > 200) were investigated. All had recto-sigmoid inflammation on endoscopy.
Each patient was given a single infusion of infliximab (5 mg/kg bodyweight) and was followed for 16 weeks. Secretion capacity for TNF-a was assessed in whole-blood cytokine assays. Nuclear concentrations of nuclear factor kappa B (kB) p65 were determined in colonic mucosal biopsy samples.
88% of patients were in remission (CDAI < 150) after 1 week, 42% at 4 weeks, 21% at 8 weeks, and 8% at 12 and 16 weeks. 29% of patients who reached remission in week 1 relapsed at week 4, 62% at week 8, 81% at week 12, and 90% at week 16.
On the first day after infusion, infliximab was found to down-regulate secretion of TNF-a to undetectable concentrations in all patients. A rise in TNF-a secretion capacity was characteristic of relapse. An increase in mucosal nuclear NFkB p65, before reactivation of clinical symptoms, was also indicative of relapse.
The group concluded that infliximab greatly improved clinical symptoms in 88% of patients with Crohn's disease after 1 week. Response in some patients was of short duration. Reactivation of the mucosal and the systemic immune system precedes clinical relapse.
Reactivation of the mucosal and systemic immune system precedes clinical relapse.