The management of inflammatory bowel diseases (IBD) is undergoing a significant evolution. For conditions like Crohn’s disease and ulcerative colitis, the historical focus on symptomatic relief is increasingly being supplemented by a “treat-to-target” strategy, which prioritizes objective measures of healing, particularly endoscopic improvement. 

AbbVie‘s latest data has contributed to the paradigm shift driven by evidence suggesting that controlling visible inflammation is key to altering long-term disease outcomes. The data was presented at the United European Gastroenterology (UEG) Week in Berlin, Germany, earlier this month.

Drug and Device World also interviewed two lead investigators about new data presented. Dr. Vipul Jairath, discussing a post-hoc analysis from the SEQUENCE trial (NCT04524611) on Skyrizi (risankizumab) for Crohn’s disease, and Dr. Remo Panaccione, sharing interim real-world results from the PROFUNDUS study (NCT05494606) on Rinvoq (Upadacitinib) for ulcerative colitis, provide insights into how these findings may influence clinical practice.

Targeting Tissue-Level Healing

Dr. Jairath contextualizes the changing approach to Crohn’s disease management. “For years, we treated Crohn’s disease based primarily on symptoms,” he stated. “A patient felt better, and we considered that a success. But we’ve learned that symptomatic improvement doesn’t always correlate with what’s happening at the tissue level.”

This understanding has elevated the importance of endoscopic healing, the visual resolution of intestinal inflammation, as a critical treatment goal. Dr. Jairath explains its significance: “Endoscopic healing, meaning actual mucosal healing visible on endoscopy, has emerged as our most reliable predictor of long-term outcomes. The treat-to-target strategy in Crohn’s disease sets objective endpoints and adjusts therapy accordingly if those outcomes are not met within a recommended timeframe. This data reinforces that endoscopic healing is the right goal to pursue to achieve better long-term outcomes.”

The data he references comes from a post hoc analysis of the Phase III SEQUENCE trial. The study assessed the association between endoscopic outcomes at week 48 and clinical status at week 100 in patients with moderate to severe Crohn’s disease treated with Skyrizi. The results demonstrated that a significantly greater proportion of patients who achieved an endoscopic response at one year also achieved clinical remission at two years (67.5% vs 51.8%), steroid-free clinical remission (67.5% vs 51.8%), and normalized fecal calprotectin levels (58.8% vs 44.5%).

Dr. Jairath highlights the broader implications of these findings: “Multiple studies have shown that patients who achieve endoscopic healing have significantly lower risk of disease progression, fewer disease complications, and reduced Crohn’s-related hospitalizations and surgeries, leading to a potentially better quality of life.”

Real-World Effectiveness in Ulcerative Colitis

Concurrently, findings from the PROFUNDUS study provide a real-world perspective on treating ulcerative colitis (UC) with Rinvoq, an oral Janus kinase inhibitor. Dr. Remo Panaccione, the lead investigator, was asked how the study’s interim results compared to prior clinical trials.

“The results from the interim analysis in the PROFUNDUS study for Rinvoq demonstrated rapid effectiveness in achieving clinical response in patients with moderate-to-severe ulcerative colitis (UC) in real clinical settings in a wide variety of age ranges, providing real-world findings consistent with the efficacy and safety observed in clinical trials,” Dr. Panaccione said. He added, “We can’t directly compare the interim results of PROFUNDUS to the randomized clinical trials.”

The interim analysis included data from 490 patients. It reported that the median time to first clinical response, as measured by the daily partial Adapted Mayo Score, was four days. By the end of the induction period at week eight or 16, 79.6% of evaluable patients had achieved a clinical response.

When asked about the practical implications of this rapid response, Dr. Panaccione noted, “In this interim analysis for PROFUNDUS, Rinvoq demonstrated rapid effectiveness in achieving clinical response in patients with moderate-to-severe UC in real clinical settings in a wide variety of age ranges, consistent with the efficacy observed in clinical trials.”

Adding, “the median time to achieve the first clinical response per daily partial Adapted Mayo Score was 4 days. By the end of the induction treatment (week eight or 16), nearly 80% of patients showed clinical improvement.”

Regarding safety, the interim data through 26 weeks reported that any treatment-emergent adverse event occurred in 51.2% of patients, with serious adverse events occurring in 5.5%. Dr. Panaccione concluded, “The overall safety findings from the controlled clinical trials were generally consistent with the known safety profile of Rinvoq; no new important safety risks were observed.”

Clinical Practice Implications

The data from both studies prompt consideration of their impact on patient management. For the SEQUENCE findings in Crohn’s disease, Dr. Jairath was asked if the results argue for more proactive endoscopic monitoring.

“Generally speaking, I believe these findings support proactive management for patients with Crohn’s disease, with monitoring and treatment optimization following timeframes recommended by evidence-based clinical guidelines,” he stated.

For the PROFUNDUS study in ulcerative colitis, Dr. Panaccione summarized the key takeaway: “PROFUNDUS studied a broad range of patients with ulcerative colitis—for patients with moderate-to-severe UC, especially those who’ve failed other treatments, this data supports upadacitinib as an option that can offer fast, effective symptom control consistent with known safety profile in real-world practice, potentially avoiding the need for more invasive interventions like surgery.”

Conclusion

The findings from the SEQUENCE and PROFUNDUS studies contribute to the evolving landscape of IBD care, which increasingly emphasizes objective treatment targets and effective options across diverse patient populations.

Dr. Jairath summarized the significance of the SEQUENCE analysis: “Results from this follow-up analysis of the SEQUENCE study are encouraging for long-term management of patients with Crohn’s disease because they showed that patients who achieved endoscopic outcomes in the first year of treatment with Skyrizi experienced sustained clinical improvements after two years of treatment.”

Together, the data underscores a continuing shift towards treatment strategies aimed at achieving and maintaining deeper levels of disease control in both Crohn’s disease and ulcerative colitis. Skyrizi and Rinvoq remain AbbVie’s top-selling drugs, grossing $7.85 billion and $3.75 billion in sales in the first half of 2025.

Note: The article was updated to add the percentages of endoscopic response at one year in the post hoc analysis of the Phase III SEQUENCE trial.