The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab
- Bella Ungar1,
- Yehuda Chowers2,
- Miri Yavzori1,
- Orit Picard1,
- Ella Fudim1,
- Ofir Har-Noy1,
- Uri Kopylov1,
- Rami Eliakim1,
- Shomron Ben-Horin1,
- on behalf of ABIRISK consortium
- 1Department of Gastroenterology, Sheba Medical Center Tel Hashomer & Sackler School of Medicine, Tel-Aviv University, Ramat Gan, Israel
- 2Department of Gastroenterology, Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Institute of Technology, Haifa, Israel
- Correspondence to Dr Shomron Ben-Horin, Gastroenterology Department, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel;
- Received 11 May 2013
- Accepted 22 August 2013
- Published Online First 16 September 2013
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.