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Biologic dose de-escalation leads to variable relapse in IBD

Patients with inflammatory bowel disease (IBD) that is resistant to treatment with 5-amino-salicylates are often prescribed biologics to achieve disease control. Subsequent de-escalation of the dose reduces both drug costs and potential adverse effects, but it remains unclear whether this strategy prevent significant disease relapse.

Biologic drugs such as infliximab are used in patients with IBD such as Crohn’s disease and ulcerative colitis as a next step after failure of other therapies. The dose of biologics is escalated in an effort to achieve satisfactory disease control and improve rates of mucosal healing. However, once this has occurred, the dose can be de-escalated in an effort to maintain clinical remission. Though outright discontinuation of biologics leads to disease relapse, a team from the Department of Medicine, University of Toronto, Canada, wondered if a reduction in dosage rather than complete cessation of treatment could maintain clinical remission. They performed a systematic review for studies examining the effect of dose de-escalation and focused on clinical relapse as defined by the individual studies.

Findings
The search revealed 20 eligible studies, 18 of which were observational, one non-randomised trial and a single sub-group analysis of a randomised controlled trial including a total of 995 patients. The reported relapse rate was quite wide and ranged from 0 to 54% and the median time to relapse varied from 3.2 to 12 months. Moreover, the relapse rate depended to some extent on the de-escalation strategy. For instance, in four of the studies, dose de-escalation was reduced to below the standard dosing, leading to relapse rates of between 6 and 30%. In contrast, in eight studies where IBD patients had been initially dose escalated to standard doses, subsequent de-escalation produced relapse rates of between 10 to 41%.

In discussing these findings, the authors noted how the wide range of relapse and limited data on predictors of relapse meant that trying to identify suitable patients for dose de-escalation was challenging and called for future studies to determine suitable relapse predictors to help guide patient selection.

Citation
Little DHW et al. Effectiveness of Dose De-escalation of Biologic Therapy in Inflammatory Bowel Disease: A Systematic Review. Am J Gastroenterol 2020;115:1768–1774. doi.org/10.14309/ajg.0000000000000783



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