CHANGING THERAPY TO ACHIEVE ENDOSCOPIC HEALING IN ASYMPTOMATIC PATIENTS WITH IBD: WHEN IS PERFECT THE ENEMY OF GOOD?
Authors: Systrom Hannah , Rai Victoria , Singh Siddharth , Baidoo Leonard , Cheifetz Adam , Devlin Shane , Gecse Krisztina , Irving Peter , Kaplan Gilaad , Kozuch Patricia , Ullman Thomas , Sparrow Miles , Melmed Gil , Siegel Corey 
Published: January 2024

Abstract

INTRODUCTION
The treat-to-target strategy for inflammatory bowel disease (IBD) recommends optimizing or changing therapy in patients who have not achieved clinical remission and endoscopic healing. In asymptomatic patients, the potential benefit of changing therapy to achieve endoscopic healing is less clear, particularly since &lt;40% typically achieve endoscopic healing with current therapy. We sought to define appropriateness of changing therapy in asymptomatic IBD patients with active endoscopic inflammation.

METHODS
Using the RAND/UCLA Appropriateness Method, a panel of 9 IBD specialists considered appropriateness of changing therapy in 16 scenarios of patients with ulcerative colitis (UC) and 96 scenarios of Crohn’s disease (CD), rating them on a 9-point Likert scale as inappropriate (1-3), uncertain (4-6), or appropriate (7-9). Patients in all scenarios were asymptomatic with active endoscopic disease; variables included disease extent, behavior, prior treatment, recent disease progression, and prior disease complications. Current therapy was assumed to be optimized, so the only options were changing therapy or continuing current therapy. An additional 14 scenarios explored whether age &gt;65 years and the possibility of pregnancy within the next year influenced treatment decision-making. Initial ratings were collected via online anonymous survey, discussed at an in-person meeting, and collected as final ratings in a second anonymous survey using a modified Delphi approach. Disagreement was assessed using a validated index.

RESULTS
Panelists rated it appropriate to change therapy (i.e., expected benefit sufficiently exceeds expected negative consequences) in 96/126 scenarios, generally those with progressive, complicated, and/or extensive disease; 27 scenarios of patients with mild and/or stable disease were rated uncertain, particularly in those with prior exposure to ≥3 drug classes (Table). Changing therapy in asymptomatic patients was rated inappropriate in three scenarios: in patients with UC Mayo 1 disease previously treated with ≥3 therapy classes with no endoscopic progression in the last year; in any patient who showed endoscopic improvement over the last year; and in any patient with CD who had only scattered aphthous ulcers. Patient age &gt;65 years influenced a decision to change therapy specifically for anti-TNFs and JAK inhibitors; the possibility of pregnancy also influenced decision-making. Despite variability in ratings, the threshold for disagreement was not crossed for any scenario.

CONCLUSIONS
Our panel of IBD specialists rated appropriateness of changing therapy to achieve endoscopic healing in asymptomatic patients with UC and CD in a variety of scenarios. Our findings can be used to help guide clinical decision-making in this population until data from ongoing randomized studies are available (NCT05230173).