Editorial: adalimumab dose escalation is effective for managing secondary loss of response in Crohn's disease
Year: 2014
Type: editorial
Abstract: Loss of response to anti-TNF agents is a common problem, for a variety of reasons that have been reviewed elsewhere.1 The reaction to this problem in practise has been to empirically increase the dose or frequency of the anti-TNF to try and re-capture clinical response and remission, with mixed short-term results.2 The recent study by Ma et al. provides additional data on the long-term results of empiric dose escalation of adalimumab in patients with Crohn's disease.3 They retrospectively measured the clinical response to weekly adalimumab dosing in patients who had lost response to every other week dosing. Similar to other observational studies, they noted that about 80% of patients responded to weekly dosing, for an average of 69 weeks. Unfortunately, over half of these patients lost response again over time, within an average of 50 weeks. Only concurrent glucocorticosteroid use was significantly associated with an individual's response to adalimumab dose escalation, making one wonder if it was actually the glucocorticosteroids making them feel better. Retrospectively measured outcomes, like in this study, are always subject to confounding factors that limit the robustness of the conclusions. In the absence of adalimumab drug levels, and objective assessment of endoscopic inflammation, we do not know if the 'clinical response' to dose escalation reflected improved pharmacokinetics, or just a placebo effect.4 This is particularly an issue in patients with Crohn's disease, where overlap complications are common, and physician-reported symptom scores are known to be sensitive to non-inflammatory symptoms.5, 6 However, this type of study does reflect clinical experience, and provides the gastroenterologist with a reference point for their patients' expectations using similar measures of success ('clinical response'). A scientific and economic case is currently being made for dose escalation based on drug levels in patients who lose response, rather than empiric escalation for all.7, 8 In the absence of individualised dosing based on drug levels, empiric dose escalation of adalimumab appears to improve patients' symptoms in the medium term.2 As new agents become available for inflammatory bowel disease (for example vedolizumab, tofacitininb and ustekinumab), the choice of dose escalation or class switch in this setting will become more nuanced and personalised.9 Declaration of personal interests: None. Declaration of funding interests: the author has received grant support from Pfizer (to BIDMC), and consulting fees for advisory boards from Janssen, Abbott, Roche and Bayer.
DOI: 10.1111/apt.12966
Author: A. C. Moss
Institutions: Beth Israel Deaconess Medical Center, Harvard University
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W3141101440