A long-term follow-up analysis of the PROFILE (Predicting Outcomes for Crohn's Disease Using a Molecular Biomarker) randomized clinical trial indicated that early intensive therapy for Crohn’s disease may substantially improve long-term clinical outcomes compared with an accelerated step-up treatment approach, according to data presented at Digestive Disease Week® (DDW) 2026.
The PROFILE trial enrolled 386 adults with newly diagnosed, active Crohn’s disease and randomized them to either early “top-down” therapy using infliximab plus an immunomodulator or an accelerated “step-up” strategy using conventional therapies with later escalation. After the 48-week trial period, participants were followed in routine clinical care for up to approximately five years (median follow-up 1,352 days). The analysis included 357 patients (92%) with available follow-up data and evaluated outcomes such as abdominal surgery, hospitalization, and progression to more advanced disease behavior.
Across the follow-up period, outcomes consistently favored the early intensive treatment group. The investigators reported that “[Crohn’s disease]-related abdominal surgeries were more frequent in [step-up] compared to [top-down] patients.” In total, there were 27 surgeries in 25 patients initially assigned to step-up therapy compared with 6 surgeries in 6 patients in the top-down group. The study also found that progression to more complicated disease behavior was more common in the step-up group (33 vs. 13 cases), and Crohn’s-related hospital admissions excluding surgery were higher as well.
“Over 4 years follow-up, ‘top-down’ treatment was associated with reduced disease progression (2x), reduced hospitalization (3x), and reduced need for abdominal surgery (5x),” the authors wrote, summarizing the overall impact of early therapy. “Early and effective control of inflammation is associated with a modified course of Crohn’s disease and should be considered the standard-of-care treatment strategy from diagnosis.”
Clinically, these findings support a shift toward earlier use of advanced therapies in patients with Crohn’s disease at diagnosis, rather than waiting for stepwise escalation after treatment failure. The data suggest that early inflammatory control may not only improve short-term outcomes but also reduce long-term complications, including the need for surgery. If validated broadly, these results may further support reconsideration of traditional step-up treatment paradigms in favor of earlier biologic-based strategies in appropriate patients.
Study author Nurulamin Noor, MD, PhD, clinical lecturer in gastroenterology at the University of Cambridge, told GI & Hepatology News there has been debate for many years on whether it is possible to modify the course of Crohn’s disease.
“The PROFILE trial long-term data demonstrated that early and effective control of inflammation from diagnosis, resulted in significantly lower risk of complications for patients including fewer abdominal surgeries, fewer hospitalizations and substantially lower progression to stricturing and penetrating complications of Crohn’s disease,” Dr. Noor said. “These 5-year data from PROFILE provide the most robust evidence to date that the course of Crohn’s disease is indeed modifiable with early effective therapy initiated from diagnosis.”
Dr. Noor disclosed serving on the speakers bureau for AbbVie, Bristol Myers Squibb, Celltrion, Ferring, Johnson & Johnson, Lilly, Pfizer, Pharmacosmos, and Tillotts, and as a scientific/medical advisory board member for AbbVie, Pfizer, and Takeda.
DDW is AGA’s annual meeting, jointly sponsored by AGA, AASLD, ASGE, and SSAT. Learn more at ddw.org.