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Therapeutic goals in Crohn's disease (CD) have moved from controlling symptoms to achieving deep remission -- that is, clinical and endoscopic remission when steroid-free. However, little is known about the long-term impact of achieving early deep remission in this disease.

To help close this data gap, David Laharie, MD, of the Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux in France, and colleagues conducted a follow-up analysis of the TAILORIX trial of tailored treatment for early CD. Beyond the 1-year study period, they found that early achievement of remission goals did not translate into better outcomes in terms of progression.

Laharie discussed the updated results, recently published in , with the Reading Room.

What was the impetus for this follow-up analysis?

Laharie: We wanted to see what happened to patients in the who received infliximab [Remicade] in combination with an immunosuppressant for 1 year. Our aim was to determine the longer-term disease course beyond the study period.

What was the study's design and sample population?

Laharie: We compared the outcomes of patients who did or did not reach the primary endpoint of the TAILORIX trial, defined as sustained corticosteroid-free clinical remission from weeks 22 through 54, with no ulcers on ileocolonoscopy at week 54. The primary outcome of this follow-up analysis was the progression-free survival of CD as defined by anal or major abdominal surgery, CD-related hospitalization, or the need for a new systemic CD treatment.

The cohort consisted of biologic-naive adults with an active uncomplicated luminal CD defined by a Crohn's Disease Activity Index of >220 associated with C-reactive protein of >5 mg/L and/or fecal calprotectin of >250 mg/g with visible endoscopic ulcers having an indication to begin anti-tumor necrosis factor (TNF) therapy in accordance with national guidelines and reimbursement criteria.

What emerged from the update?

Laharie: Simply put, the achievement of complete mucosal healing defined by a Simplified Endoscopic Score for Crohn's Disease (SES-CD) of 0 did not lead to less disease progression.

The 95 patients who achieved the primary TAILORIX endpoint were followed for a median duration of 64.2 months after the study period ended. Of the 95, 47% achieved the primary endpoint and 53% did not. We saw no significant difference in progression-free survival at 1, 3, and 5 years between patients who achieved the primary endpoint and those who did not.

No difference was observed between the two groups for each component of progression we looked at: anal surgery, major

abdominal surgery, CD-related hospitalization, or the need for a new systemic CD treatment.

Were you disappointed with the results?

Laharie: Honestly, we were convinced that achieving deep remission would be more favorable for CD patients. Our findings were unexpected. That's why we analyzed our cohort more deeply looking at a SES-CD of 0 for each component of CD progression, but again finding no difference between the two groups

What has other research in this area shown?

Laharie: The long-term impact of achieving clinical and endoscopic remission on the disease course of CD has been studied in a few cohorts. A of 10 studies published in 2015, for example, found mucosal healing to be significantly associated with long-term clinical remission. And in a 2019 retrospective single-center , complete endoscopic remission was associated with better outcomes than partial remission.

What about study limitations?

Laharie: Follow-up data were collected retrospectively, and since the present analysis was built on the TAILORIX trial, the sample size could not be changed and was therefore not powered to compare long-term progression-free survival between the two groups.

What's the clinical bottom line that emerges from your findings?

Laharie: Our data support the early use of aggressive treatments to modify the history of CD. We also need to take a more flexible approach to the treat-to-target concept in daily practice in order to better manage patients.

What does future research look like?

Laharie: The cutoff for defining endoscopic remission in CD remains unknown. We need prospective trials to better define therapeutic goals that actually change the natural course of the disease and prevent complications.

You can read the abstract of the study here, and about the clinical implications of the study here.