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- Title
Long-Term Outcome of Infliximab Optimization for Overcoming Immunogenicity in Patients with Inflammatory Bowel Disease.
- Authors
Papamichael, Konstantinos; Vajravelu, Ravy K.; Osterman, Mark T.; Cheifetz, Adam S.
- Abstract
<bold>Background: </bold>Preliminary data suggest that treatment optimization can reverse immunogenicity and regain response in patients with IBD and secondary loss of response (SLR) to anti-TNF therapy due to antidrug antibodies. However, data regarding the long-term outcome of these patients are scarce.<bold>Aims: </bold>We aimed to investigate drug retention in IBD patients of whom infliximab was optimized to overcome immunogenicity and variables associated with drug retention.<bold>Methods: </bold>This was a retrospective, multicenter study of consecutive IBD patients with antibodies to infliximab (ATI), based on either proactive or reactive therapeutic drug monitoring, who underwent infliximab optimization (increasing dose, shortening interval, adding an immunomodulator, or combination) to overcome immunogenicity from September 2012 to July 2015; they were followed through December 2015. ATI were analyzed using the drug-tolerant Prometheus homogeneous mobility shift assay. Drug retention was defined as no need for drug discontinuation due to SLR or serious adverse event.<bold>Results: </bold>Our cohort consisted of 22 patients (Crohn's disease, n = 15). At the end of follow-up [median, (IQR): 17.3 (10.5-32.8) months] 77% (15/22) of patients were still on drug. Univariable Cox proportional hazards regression analysis identified first detectable ATI titer as the only variable associated with drug retention (HR: 0.89; 95% CI: 0.82-0.98, p = 0.016). Receiver-operating characteristic analysis identified an ATI titer < 8.8 U/mL associated with drug retention.<bold>Conclusions: </bold>In real-life clinical practice, optimization of infliximab therapy can prevent drug discontinuation in approximately 3/4 of patients with ATI, especially in those with low titers. Large prospective studies are needed to confirm these data.
- Subjects
INFLAMMATORY bowel disease treatment; INFLIXIMAB; DRUG monitoring; RETROSPECTIVE studies; MATHEMATICAL optimization; COMPARATIVE studies; DRUG tolerance; DRUG administration; DOSE-effect relationship in pharmacology; GASTROINTESTINAL agents; INFLAMMATORY bowel diseases; RESEARCH methodology; MEDICAL cooperation; RESEARCH; RESEARCH funding; TUMOR necrosis factors; EVALUATION research; DISEASE remission
- Publication
Digestive Diseases & Sciences, 2018, Vol 63, Issue 3, p761
- ISSN
0163-2116
- Publication type
journal article
- DOI
10.1007/s10620-018-4917-7