Effect of Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction on Disease Remission in Patients With Chronic Immune-Mediated Inflammatory Diseases

Abstract

IMPORTANCEProactive therapeutic drug monitoring (TDM), defined as individualized drug dosing based on scheduled monitoring of serum drug levels, has been proposed as an alternative to standard therapy to maximize efficacy and safety of infliximab and other biological drugs. However, whether proactive TDM improves clinical outcomes when implemented at the time of drug initiation, compared with standard therapy, remains unclear.OBJECTIVE To assess whether TDM during initiation of infliximab therapy improves treatment efficacy compared with standard infliximab therapy without TDM. DESIGN, SETTING, AND PARTICIPANTS Randomized, parallel-group, open-label clinical trial of 411 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis initiating infliximab therapy in 21 hospitals in Norway. Patients were recruited from

Model-Informed Precision Dosing during Infliximab Induction Therapy Reduces Variability in Exposure and Endoscopic Improvement between Patients with Ulcerative Colitis

“…MIPD of infliximab has been implemented in clinical practice mainly in tertiary care centers, however, even there, the confidence in MIPD is crumbling as the results of the landmark TAXIT, TAILORIX, and NOR-DRUM trials do not live up to expectations [ 12 , 14 , 31 ]. Our research showed that in silico simulations are a low-cost alternative to these clinical studies.…”

“…To date, most therapeutic drug monitoring (TDM) studies of infliximab focus on maintenance therapy, whereas induction therapy is relatively unexplored. Moreover, the utility of TDM of infliximab in patients with UC remains controversial because of poor evidence from prospective TDM studies [ 10 , 12 , 13 , 14 ]. One potential reason for the weak evidence can be the use of inefficient TDM algorithms (analogous flowcharts and decision trees) in these TDM studies [ 15 ].…”

Seasoning to Perfection: How to Optimize Anti-TNF Therapy

“…Some studies suggest that therapy can be optimized by monitoring for the development of ADAbs, determining trough drug levels and/or measuring the bioactivity of the monoclonal antibody, 10 while other reports concluded that such monitoring rarely adds to therapeutic decision-making. 11,12 A related question is whether the addition of an anti-metabolite-like methotrexate to anti-TNF therapy could reduce the likelihood that neutralizing antibodies will develop. Such a strategy is plausible but must be weighed against the additional risk, cost, and inconvenience of a second immunosuppressive medication.…”

“…However, thus far in clinical trials, therapeutic drug monitoring of TNF-inhibitors does not improve clinical outcomes. 12,14 There are likely multiple reasons for this, including differences in underlying disease, variability in assays measuring ADAbs and variability in ADAbs themselves. Most assays measure binding of the antibody to the drug without measuring the in vivo neutralizing effect of the ADAb, and thus may detect ADAbs of little clinical significance.…”

“…15 It is not surprising that patients may have ADAbs and be in remission. 12 Changing therapy purely based on therapeutic drug monitoring may not improve clinical outcomes. 15 Given these limitations, one could argue that monitoring the patient's disease is more important than attempting by a laboratory test to predict treatment failure, particularly in an organ lending itself well to monitoring, such as the joint, skin, or eye.…”