In routine practice for chronic inflammatory bowel disease (IBD), drug therapy is usually escalated stepwise. New study data presented at the 21st Congress of the European Crohn’s and Colitis Organisation, 2026, Stockholm, Sweden, argue for early intensive therapy — a top-down strategy — particularly for Crohn’s disease (CD).

Nurulamin Noor of the University of Cambridge, Cambridge, England, presented 5-year follow-up data from the PROFILE trial. In the randomized study, 386 patients with newly diagnosed CD were assigned within 14 days of diagnosis either to a top-down regimen of infliximab plus an immunomodulator or to an accelerated step-up strategy with an option for early escalation.

Marked Reduction in Surgeries

At 48 weeks, there was already a clear benefit for early intensive therapy: 79% of patients in the top-down arm achieved steroid-free remission, compared with 15% in the step-up arm. Fewer complications occurred, in particular a “10-fold reduction in the need for abdominal surgery,” Noor emphasized.

Long-Term Surgery Risk

Follow-up data were available for 357 patients in the long-term analysis. After completion of the 48-week study protocol, patients continued to be treated according to local standards. “More than half of the patients in the step-up arm had already received a [TNF‑alpha] inhibitor in the first year,” Noor reported. “And yet the need for abdominal surgery continued to rise.”

Over the entire observation period from diagnosis, 28 patients in the step-up arm required an abdominal procedure, compared with six patients in the top-down arm. “The risk of an abdominal procedure was about four times higher under the step-up strategy,” Noor said.

Disease progression and hospitalizations were also more common under the initial step-up strategy. “We observed in the step-up arm the typical progression to stricturing and penetrating disease,” Noor explained. The risk for progression to B2 or B3 disease was significantly increased (relative risk, 2.50). In contrast, only a very small proportion of patients in the top-down arm developed penetrating disease.

Hospitalizations due to CD — excluding abdominal surgery — were also more frequent in the step-up arm (relative risk, 1.64). In addition, surgeries, disease progression, and hospital admissions occurred earlier in this group.

Safety Concerns Reassessed

Historically, there have been reservations about an early top-down approach, particularly over safety concerns and the fear of overtreatment. “Over 5 years of follow-up, we found no difference in serious infections or malignant disease between the groups,” Noor said.

His conclusion: “Early effective therapy can sustainably change the course of CD and should be considered as a treatment standard from the time of diagnosis.”

NORDTREAT Includes UC And CD

The NORDTREAT study also offers evidence supporting early intensive therapy — for patients with CD. Jonas Halfvarson, MD, of the Department of Gastroenterology at Örebro University Hospital in Örebro, Sweden, reported the results.

Unlike PROFILE, NORDTREAT enrolled patients with both CD and ulcerative colitis (UC). Moreover, early intensive therapy was not applied universally but only to patients with a high‑risk profile defined by a prognostic protein signature.

A total of 314 adults with newly diagnosed IBD were randomized a median of 7 days after diagnosis. Depending on study arm, the treating physicians either had access to the prognostic protein signature or did not.

Selective Top-Down for High‑Risk

In the group where the protein signature was disclosed, high‑risk patients received early top-down therapy with a TNF‑alpha inhibitor with or without an immunomodulator. Patients with a low‑risk signature were excluded from the study. In the group in which the signature was concealed, therapy for all patients was left to clinical judgment with stepwise escalation.

Of the 157 patients with a disclosed protein signature, 24 (15%) had a high‑risk pattern. In the group without disclosure, retrospectively, 29 (19%) would also have been classified as high risk. Of those, 16 (55%) eventually received advanced therapy, but later. Halfvarson reported that patients whose signature was known received a biologic on average 21 days after diagnosis, while those in the group without a known protein signature received it only after 44 days.

Primary Endpoint Not Met

The primary endpoint — steroid‑free clinical and endoscopic remission at 52 weeks — was achieved by 42% (10 of 24) of high‑risk patients who received early intensive therapy, compared with 27% (8 of 29) who underwent step‑wise escalation. “The difference was numerically present but not statistically significant,” Halfvarson said.

When clinical and endoscopic remission were analyzed separately, there was a significant difference favoring early intensive therapy for clinical remission (76% vs 48%; P = .047), but not for endoscopic remission (54% vs 45%; P = .56).

Serious complications — mostly hospitalizations related to worsening IBD — occurred in 8 of 24 patients receiving early top‑down therapy vs 14 of 29 patients receiving step‑up escalation. One death was reported in the step-up arm, in a patient with UC following colectomy.

Limited UC Benefit

Post hoc analyses indicated that patients with CD were more likely to benefit from a top-down strategy than those with UC: 50% reached the primary endpoint under top-down therapy vs 11% under stepwise escalation. For UC, the rates were nearly identical at 36% vs 35%.

For Halfvarson, this means a biomarker‑guided, top-down strategy does not appear to raise remission rates across IBD in general; however, the data suggest a possible benefit of early intensive therapy in Crohn’s disease, he emphasized.

This story has been translated from the Medscape German edition.