The treatment strategy for ulcerative colitis [UC] is mainly based on the severity, distribution [proctitis, left-sided, extensive]¹ and pattern of disease. The latter includes relapse frequency, disease course, response to previous medications, side effects of medication, and extra-intestinal manifestations. Age at onset, and disease duration are also important factors. It is important to distinguish patients with severe UC necessitating hospital admission from those with mild or moderately active disease who can be managed as outpatients. The best validated and most widely used index for identifying severe UC remains that of Truelove and Witts.² Patients with bloody stool frequency ≥ 6/day and a tachycardia [> 90 min⁻¹], or temperature > 37.8°C, or anaemia [haemoglobin < 10.5 g/dl], or an elevated erythrocyte sedimentation rate [ESR] [> 30 mm/h] have severe UC. Only one additional criterion in addition to the bloody stool frequency ≥ 6/day is needed to define a severe attack.^3,4 In practice, a C-reactive protein [CRP] of 30 mg/l can be substituted for the ESR.

Hannah Gordon, Silvia Minozzi, Uri Kopylov, Bram Verstockt, Maria Chaparro, Christianne Buskens, Janindra Warusavitarne, Manasi Agrawal, Mariangela Allocca

Objective To characterise the temporal evolution of antibodies to infliximab (ATI). Design Prospective observational study of infliximab-treated patients with inflammatory bowel disease between 2009 and 2012. Interventions Trough levels of infliximab and ATI were measured before each infusion by anti-λ ELISA. Patients were monitored for disease activity by clinical activity indexes and for dose-intensification or infliximab cessation. The occurrence of transient ATI disappearing spontaneously without intervention was recorded separately. Results 125 patients were included (98 Crohn's disease, 27 ulcerative colitis, median follow-up 11.5±22 months) and 1119 sera were analysed for infliximab and ATI levels. Kaplan-Meier analysis showed that 42% of patients remained ATI-free by 4 years of treatment. Most (90%) of the patients who developed ATI did so within the first 12 months of therapy, whereas transient ATI were detected throughout the duration of infliximab therapy (p<0.001). ATI incidence was similar between patients who received infliximab previously (episodic/interrupted therapy patients, n=14) and scheduled-therapy patients (n=111). In the scheduled group, combination immunomodulator+infliximab resulted in longer ATI-free survival compared with monotherapy (p=0.003, logrank test). Survival free of clinical loss of response was enjoyed by 51% of patients, and serial measurements showed that ATI development often preceded the onset of clinical flare. Conclusions When followed prospectively, most patients who develop ATI do so within the first 12 months of therapy. This incidence is reduced by concomitant immunomodulator even in scheduled-therapy patients. In contrast, transient ATI, which are of little clinical significance, can appear haphazardly at any time during treatment. The onset of clinical loss of response may lag behind the appearance of anti-infliximab antibodies.