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PROFILE 4-year follow-up shows that early effective “top-down” therapy is associated with reduced long-term Crohn’s disease complications

N. Noor, H. Zheng, M.T. Sharip, J. Lee, D. Robertson, M. Parkes, PROFILE Study Group

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Slides compiled by Dr. Reena Khanna

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Introduction

Background & Objectives

    • In the original PROFILE RCT (48 weeks): “top-down” (TD; infliximab + immunomodulator) therapy from diagnosis led to better outcomes vs accelerated “step-up” (SU; conventional) treatment.
      • Abdominal surgeries: 10 in SU vs. 1 in TD
    • Objective: Determine whether early effective treatment (TD vs SU) modifies the longer-term course of CD with follow-up of PROFILE participants.

CD, Crohn’s Disease; ITT, intention-to-treat; OR, odds ratio; CI, confidence interval.

Noor N et al. ECCO 2026; (Abstract citation ID: jjaf231.005, OP05).

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Methods

    • Design: Medical record review for objective outcomes for up to 5 years after the week-48 end-of-trial visit.
    • Population: PROFILE RCT participants (Adults with newly diagnosed active Crohn’s disease at trial start); post-trial management per local standard of care
    • Outcomes: CD-related abdominal surgery; hospital admission and progression to stricturing [B2]/ penetrating [B3] disease
    • Analysis: Based on PROFILE randomization and modified ITT; ORs (95% CI) for outcomes; time-to-event via Kaplan–Meier and Cox proportional hazards models.

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Patient Characteristics

TD, top-down treatment group; SU, step-up treatment group

Noor N et al. ECCO 2026; (Abstract citation ID: jjaf231.005, OP05).

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Follow-up Population

    • PROFILE RCT (48 weeks): N=386
    • PROFILE follow-up: N=357 (92%)
      • 180 TD
      • 177 SU
    • Median follow-up was 1352 days (∼4.5 years from diagnosis).

Treatment Exposure

    • PROFILE patients receiving anti-TNF:
      • 100% TD
      • 41% SU
    • Post-PROFILE patients receiving advanced therapy:
      • 100% TD
      • 78% SU.

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Results: Abdominal Surgeries

Post-PROFILE period:

    • SU: 17 surgeries
    • TD: 5 surgeries

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From diagnosis (aggregate):

    • SU: 27 surgeries (25 patients)
      • 25/27 for CD complications (12 stricturing [B2], 13 penetrating [B3])
    • TD: 6 surgeries (6 patients)
      • 5/6 for CD complications (3 B2, 2 B3).

TD, top-down treatment group; SU, step-up treatment group

Noor N et al. ECCO 2026; (Abstract citation ID: jjaf231.005, OP05).

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Total number of abdominal surgeries

Time to first abdominal surgery

OR = 5.00; 95% CI 2.02-12.43; p<0.001

Earlier time to first surgery in SU

Incidence of Crohn’s disease abdominal surgery

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Results

TD, top-down treatment group; SU, step-up treatment group; OR, odds ratio; CI, confidence interval; CD, Crohn’s Disease

Noor N et al. ECCO 2026; (Abstract citation ID: jjaf231.005, OP05).

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Progression to stricturing [B2] / penetrating [B3] disease:

    • More frequent in SU vs TD (33 vs 13)
      • OR = 2.61; 95% CI 1.33-5.12

Incidence of CD-related hospital admissions (excluding surgeries):

    • Higher in SU vs TD (44 vs 15)
      • OR = 3.75; 95% CI 2.00-7.02

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Conclusions

    • Although most patients in the step-up group eventually received biologic therapy, the need for surgery, hospitalization and development of stricturing disease was higher in this population compared to the top-down group.

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Significance to clinical practice

    • Early effective therapy may have long term benefits to patient outcomes.
    • This is thought provoking to consider disease modification as possible with therapy choices.

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Noor N et al. ECCO 2026; (Abstract citation ID: jjaf231.005, OP05).

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