High prevalence of antibodies to infliximab and their relation to clinical outcomes in inflammatory bowel disease patients

Abstract

Summary Background Antibodies to infliximab (ATI) can complicate infliximab (IFX) treatment of inflammatory bowel disease (IBD) patients. Aims To identify a clinically relevant threshold for ATI using a drug‐tolerant assay and to clarify factors for ATI development and their relation to clinical outcomes. Methods A cohort study of all IBD patients receiving IFX from May 2016 to April 2017 at a tertiary referral centre. Clinical data and serial therapeutic drug monitoring (at every infusion after the first) were collected. Results Over 12 months follow‐up, 113/214 (53%) patients had positive ATI, 94/214 (44%) had negative ATI and 7/214 (3%) had transient ATI. Concomitant immunosuppression was negatively associated with ATI positivity: thiopurines OR 0.48, methotrexate OR 0.36. ATI formation was more likely to be preceded by subtherapeutic IFX levels (57%) than vice versa (9%). Positive ATI were significantly associated with infusion reactions, loss of clinical remission and a reduction in IFX levels. In patients positive for ATI at first maintenance dose, 71% were treatment failures by second maintenance dose compared to 28% in those with negative ATI (P < .01). An ATI threshold of 2.5 mg/L had a sensitivity of 0.78 and a specificity of 0.63 in detecting loss of clinical remission ≤8 weeks. Conclusions There is a high prevalence of positive ATI and subtherapeutic IFX in IBD patients. Early ATI post induction is associated with a high rate of rapid treatment failure. ATI are significantly associated with loss of clinical remission. A lower ATI threshold of 2.5 mg/L has high sensitivity for loss of clinical remission.

Editorial: proactive therapeutic drug monitoring in treatment of inflammatory bowel disease: it makes sense

“…It may seem to be self‐fulfilling prophecy that by proactively monitoring drug levels and antibodies in biological therapy, physicians can achieve better disease control . However, even the most obvious treatment propositions need to be demonstrated by a prospective study.…”

“…However, even the most obvious treatment propositions need to be demonstrated by a prospective study. In the previous issue of GastroHep, Tun et al demonstrated that there is a high prevalence of positive antibodies to infliximab (ATI) post‐induction and is associated with a high rate of rapid treatment failure . In this issue, McGettigan et al conducted a prospective cohort study following the clinical course of two groups of patients, one with reactive monitoring and the other with proactive drug monitoring …”