Proactively Optimized Infliximab Monotherapy Is as Effective as Combination Therapy in IBD

Abstract

Infliximab durability did not differ between patients on IFX monotherapy dosed based on p-TDM and patients receiving combination therapy. In the absence of concomitant immunosuppression, proactive TDM may improve IFX durability by maintaining higher IFX concentrations entering into maintenance. Further studies are needed to confirm our findings.

Optimised infliximab monotherapy is as effective as optimised combination therapy, but is associated with higher drug consumption in inflammatory bowel disease

“…Similar results have recently been observed by Lega et al in a cohort study of 83 patients with a 1‐year follow‐up where early infliximab dose escalations triggered by week 10 induction drug levels resulted in similar clinical outcomes and similar infliximab trough levels regardless of treatment strategy. Our results show that similar success of infliximab monotherapy can also be achieved by introducing therapeutic drug monitoring at a later time point.…”

“…In conclusion, in this study of 149 infliximab‐treated patients between 2011 and 2016, where the management of patients included all the modern aspects of treatment optimisation, such as early and liberal infliximab dose escalations, both reactive and proactive, supported by therapeutic drug monitoring, we were able to appreciate that azathioprine co‐treatment had no impact on the long‐term clinical outcome of patients and only a transient infliximab‐sparing effect for the duration of azathioprine co‐treatment. Our results, together with the findings of others indicate that routine use of azathioprine co‐treatment during introduction of infliximab in patients who previously failed azathioprine is questionable. The efficacy, safety and cost‐effectiveness of optimised infliximab monotherapy should be evaluated in a prospective study.…”

“…For the same reason, controlled trials with longer observation periods are unlikely to be designed, and we believe that our data on the very limited clinical benefit of a short‐term combination strategy for the initiation of infliximab add important new knowledge to this area. Despite all the intrinsic limitations of cohort studies, we believe that our results, together with the findings of others, provide an important step towards understanding the limited added value of routine azathioprine co‐treatment in the era of affordable therapeutic drug monitoring. Although our observations indicate that the starting strategy, with or without azathioprine, does not impact the drug‐to‐trough ratio in the long term, it is nevertheless important to discuss the increased cost of optimised infliximab monotherapy during the first year of treatment with the payers as budget constraints of many countries might prevent the use of higher doses of infliximab.…”

Appropriate Therapeutic Drug Monitoring of Biologic Agents for Patients With Inflammatory Bowel Diseases

“…38,39,103,104,128 Furthermore, numerous retrospective studies 23,24,26,29,[31][32][33]67,73,74,[77][78][79]129,130 and some post hoc analyses of RCTs [47][48][49]71,76,94,131,132 have shown that higher biologic drug concentrations are associated with favorable short-term and long-term therapeutic outcomes in IBD (Supplementary Table 1, Tables 1 and 2). There do appear to be certain clinical scenarios that proactive TDM of anti-TNF therapy can efficiently guide therapeutic decisions, such as treatment de-escalation, 133 the application of optimized monotherapy instead of combo therapy with immunomodulator, 82 restarting therapy after a long drug holiday, 27 and treatment cessation on deep remission. 50,51 Nevertheless, before TDM can be widely applied in clinical practice, there are several obstacles to their regular use including when to use TDM, how to accurately interpret and apply the results of such testing, and in defining the optimal drug concentration thresholds and ranges to target.…”

“…38,39,103,104 Moreover, proactive TDM may also improve the cost-effectiveness and safety of biologic therapy via the implementation of a de-escalation strategy in patients with supratherapeutic drug concentrations by reducing the dose, increasing the time interval, and/or stopping the immunomodulator in patients on combination therapy (optimized monotherapy). 39,82,[105][106][107] However, there are still some limitations when applying TDM into clinical practice, such as when to use TDM, proper interpretation and application of the results, and the identification of the optimal window/ thresholds to target. These therapeutic windows or thresholds appear to vary on the basis of the outcome of interest and the IBD phenotype (Tables 1 and 2, Supplementary Table 1).…”