It should be acknowledged, however, that the earlier-described hypothesis is not supported
by the results of several studies that have shown the benefits of increasing the infliximab dose in some patients with IBD or rheumatoid arthritis who lose response.27 and 28 Nonetheless, these findings suggest that clinicians should carefully weigh the need for a dose adjustment when applicable, considering that not all patients may benefit from such a dose increase. The current results had some limitations. First, although the relationship between serum XL184 infliximab concentrations and efficacy outcomes appears to be both consistent and robust, these results are retrospective and may have been confounded by other determinants of both drug concentrations and outcomes. These data, however, were generated from large randomized trials in which known confounders were identified prospectively and in which randomization would be expected to result in an even distribution of confounding variables between the experimental groups. Nevertheless, prospective studies designed to assess the value Selleck Neratinib of infliximab concentration–guided dose escalation in terms of efficacy and potential impact on safety could provide valuable information pertaining to a more optimized approach toward infliximab therapy of UC. One such study suggests that therapeutic drug monitoring may predict the likelihood of
achieving mucosal healing after infliximab dose escalation in IBD.29 The positive findings of a small randomized trial of therapeutic drug monitoring in patients with Crohn’s disease who experienced a loss of response to infliximab also are encouraging.30 It also generally is held that a therapeutic drug monitoring approach using treatment algorithms in the management of secondary loss of response may be more rational than empiric dose escalation.31 The results of these analyses also may be limited by the fact that GBA3 the serum infliximab concentrations were measured using
a proprietary assay not presently available commercially. As a result, research is needed to cross-validate the assay with those available to physicians to help translate these identified infliximab concentrations into practice settings. In addition, the low NPV and low positive likelihood ratio associated with the identified threshold imply that false-negative results may be common and additional clinical judgment will be needed to manage patients who show concentrations less than the target threshold. Conversely, the magnitude of the PPV at the identified thresholds may reassure a clinician that a given patient is not undertreated if serum drug concentrations are greater than these thresholds. In summary, we have established that there is a strong association between serum infliximab concentration and efficacy outcomes in patients with UC.