De-escalation of biological therapy in inflammatory bowel disease patients following prior dose escalation

Abstract

Background: Limited data are available on biological therapy de-escalation after prior escalation in inflammatory bowel disease (IBD) patients. This study aimed to assess the frequency and success rate of de-escalation of biological therapy in IBD patients after prior dose escalation and to evaluate which measures are used to guide de-escalation.

Methods: This multicentre retrospective cohort study enrolled IBD patients treated with infliximab (IFX), adalimumab (ADA) or vedolizumab (VEDO) in whom therapy was de-escalated after prior biological escalation. De-escalations were considered pharmacokinetic-driven if based on clinical symptoms combined with therapeutic or supratherapeutic trough levels, and disease activity-driven if based on faecal calprotectin less than or equal to 200 µg/g or resolution of perianal fistula drainage or closure or endoscopic remission. Successful de-escalation was defined as remaining on the same or lower biological dose for greater than or equal to 6 months after de-escalation without the need for corticosteroids.

Results: In total, 206 IFX users, 85 ADA users and 55 VEDO users underwent therapy escalation. Of these patients, 34 (17%) on IFX, 18 (21%) on ADA and 8 (15%) on VEDO underwent therapy de-escalation. De-escalation was successful in 88% of IFX patients, 89% of ADA and 100% of VEDO. The probability of remaining on the de-escalated regimen or further de-escalation after 1 year was 85% for IFX, 62% for ADA and 100% for VEDO. Disease activity-driven de-escalations were more often successful (97%) than pharmacokinetic- and no marker-driven de-escalations (76%); P = 0.017.

Conclusion: De-escalation after biological dose escalation was successful in the majority of carefully selected IBD patients. Objective assessment of remission increased the likelihood of successful de-escalation.

Fig. 1.

Flowchart de-escalation of biological therapy in inflammatory bowel disease patients. The total number of inflammatory bowel disease patients represents all patients included in the Dutch IBDREAM registry. The second step includes all patients that started the specific biological therapy after 1 January 2013. Data were extracted from the IBDREAM registry on 6 June 2020. ADA, adalimumab; IBD, inflammatory bowel disease; IFX, infliximab; VEDO, vedolizumab.

Fig. 2.

De-escalation outcomes stratified per diagnostic measure used before de-escalation. Pharmacokinetic-driven – de-escalation based on clinical symptoms and therapeutic or supratherapeutic trough levels. Disease activity-driven – de-escalation based on faecal calprotectin less than 200 µg/g, resolution of perianal fistula drainage or closure or endoscopic remission based on the absence of ulcers. Both – de-escalation based on a combination of pharmacokinetic-driven and disease activity-driven. No marker – de-escalation based on only clinical symptoms.

Fig. 3.

Kaplan–Meier survival curves demonstrating infliximab, adalimumab and vedolizumab persistence on de-escalated regimen. Median continued use of the de-escalated regimen or further de-escalation per biological therapy were as follows: infliximab 14.3 months (IQR 6.9–28.9), adalimumab 11.1 months (IQR 6.5–37.2) and vedolizumab 15.2 months (IQR 9.8–24.0). IQR, interquartile range.