Dose escalation of biologics in Crohn’s disease: critical review of observational studies

Abstract

Background: Biologics used to treat Crohn’s disease (CD) may lose their effect over time, requiring dose escalation. Little information is available on this topic.

Aim: To summarize rates of dose escalation, duration, de-escalation in observational studies of CD in adults treated with adalimumab, infliximab, and vedolizumab in Europe.

Methods: Two independent investigators searched Medline and Embase for observational studies published in 1998–2015 and proceedings from four major scientific meetings. Rates were summarized descriptively.

Results: In total, 58 articles from 12 European countries were analyzed (49 full articles, nine abstracts), providing 65 reports with 7,850 patients; 35 reported on 3,830 patients with adalimumab (ADA), and 30 on 4,020 patients with infliximab (IFX). Overall, 29.9% ± 3.5% of patients required dose escalation; 32.8% ± 6.2% with ADA and 25.2% ± 2.4% with IFX (p = .35 between drugs). Rates increased according to line of treatment: 19% for first line, 37% second, and 41% third. The median time to loss of response was 12 months, and the weighted average was 15.1 ± 5.9 months. Median time to escalation was 6.7 months; 6.7 months for ADA and 7.5 for IFX (p = .86). Short-term response rates to escalation were 63% for ADA and 45% for IFX (p = .08). There were no papers available for vedolizumab.

Conclusions: A substantial proportion of patients receiving ADA or IFX for Crohn’s disease require dose escalation after a short period of time.

Keywords:

• Crohn’s disease
• biologics
• adalimumab
• infliximab
• dose escalation

Transparency

Declaration of funding

This work was funded by Janssen Pharmaceutica NV, Beerse, Belgium.

Declaration of financial/other relationships

TRE and BGB received financial remuneration for this research and manuscript. Both have previously held contracts with Janssen and presented posters at scientific meetings. FL and XYL are employees of Janssen.