AbbVie presented a slew of data for its high-profile immunology drugs, Skyrizi (risankizumab) and Rinvoq (upadacitinib) at the European Crohn’s and Colitis Organisation (ECCO) 2026 Congress in Stockholm. The two therapies have been highest grossing drugs for the company in recent years. In 2024, Skyrizi and Rinvoq raked in $11.7 billion and $5.97 billion, respectively.

Five abstracts presented across the meeting tell a coherent story: three-year follow-up from the SEQUENCE (NCT04524611) and COMMAND (NCT03398135) open-label extension studies demonstrate sustained efficacy of Skyrizi in Crohn’s disease and ulcerative colitis; the U-ENDURE (NCT03345823) long-term extension shows Rinvoq maintains endoscopic and clinical benefits through three years; and real-world evidence from PROFUNDUS (NCT05494606) and APPRISE (NCT05841537) confirms these outcomes translate beyond controlled trial settings.

To understand what this data mean for clinical practice, Drug and Device World spoke with two investigators at the forefront of IBD research. Dr. Remo Panaccione, Professor of Medicine and Director of the Inflammatory Bowel Disease Unit at the University of Calgary, brings his perspective on the PROFUNDUS real-world study and what it reveals about Rinvoq’s performance in everyday practice. Dr. Laurent Peyrin-Biroulet, Professor of Gastroenterology and Head of the Inflammatory Bowel Disease Unit at Nancy University Hospital in France, discusses the long-term implications of the SEQUENCE data and what durability of response means for patients with moderate to severe Crohn’s disease.

The PROFUNDUS Study

The PROFUNDUS study, an ongoing international prospective observational study evaluating Rinvoq in patients with moderate to severely active ulcerative colitis, bridges both worlds.

Among the first 494 patients enrolled across 16 countries, the interim analysis presented at ECCO shows high rates of clinical and symptomatic improvement. At week 26, 81.8% of patients achieved clinical response per Partial Adapted Mayo Score, while 72.4% achieved clinical remission. Notably, among patients on corticosteroids at baseline, 64.4% attained corticosteroid-free response.

But for Dr. Panaccione, one finding stands out for its immediate clinical relevance. “In a previous interim analysis of the PROFUNDUS study we presented at UEGW, Rinvoq demonstrated rapid effectiveness in achieving clinical response in patients with moderate-to-severe ulcerative colitis in real clinical settings and in a wide variety of age ranges, consistent with the efficacy observed in clinical trials,” he explains. “Median time to achieve the first clinical response per daily Partial Adapted Mayo Score was four days.”

That speed matters when patients present with active flares. “Seeing meaningful rapid symptom relief early in treatment is obviously important for patients who are suffering through an active flare—the burden of uncontrolled disease is significant, and it can affect every aspect of daily life,” Dr. Panaccione notes. Yet he cautions against focusing exclusively on rapid onset. “That said, speed of response is only one part of the picture. When I’m making treatment decisions, I’m thinking just as carefully about the durability of that response, the tolerability profile over time, and whether a patient can sustain remission without long-term corticosteroid use.”

The PROFUNDUS data also address a question that arises frequently in clinic: will this work in patients who have failed other advanced therapies? More than half of the study population (54.6%) were advanced therapy-experienced, with 41.9% having failed at least one TNF inhibitor and 14.2% having failed a prior JAK inhibitor. The results were remarkably consistent regardless of prior treatment history.

“What’s compelling about PROFUNDUS is that it adds to the controlled conditions of a clinical trial and reflects the patients we as treating physicians actually see in our practice—over half had prior advanced therapy experience, nearly 42% had failed at least one TNF inhibitor, and some had even failed a prior JAK inhibitor,” Dr. Panaccione observes. “Clinical remission rates at week 26 were essentially identical between advanced therapy-naïve and advanced therapy-experienced patients—around 72% in both groups, which can help support the argument that Rinvoq can be effective across different points in the treatment journey.”

The symptomatic improvements extend beyond traditional disease activity measures to encompass outcomes patients prioritize. In PROFUNDUS, 66.3% of patients reported no abdominal pain at week 26, and 71.9% reported no bowel urgency.

“Bowel urgency and abdominal pain are two symptoms that patients consistently tell us have a great impact on their ability to work, socialize, and simply feel normal,” Dr. Panaccione emphasizes. “In PROFUNDUS, around 66% of patients reported no abdominal pain and nearly 72% reported no bowel urgency at week 26. The fact that these outcomes were achieved with an oral, once-daily therapy can matter from a patient experience standpoint as not everyone wants or is able to manage infusions or injections.”

The safety profile observed in PROFUNDUS aligns with what clinicians have come to expect from JAK inhibition. Among patients receiving any Rinvoq dose, 51.4% reported any adverse event, with serious adverse events occurring in 5.7% and severe adverse events in 5.5%. Dr. Panaccione contextualizes these findings: “Clinicians are getting more comfortable with the safety profile of Rinvoq as well. Specifically, in PROFUNDUS, about half of the patients had some type of adverse events, but serious adverse events happened in less than 6% of the patient population, with the vast majority of those events not related to the study drug according to the investigator.”

He adds a note of caution about longer-term follow-up: “The PROFUNDUS safety data is consistent at 26 weeks, and represents an early snapshot; longer-term follow-up will be important to fully know the risk profile, including for infections and other events associated with JAK inhibition as a class. Clinicians still need to weigh individual patient risk factors, including cardiovascular history and infection risk, when considering a JAK inhibitor.”

Despite these caveats, Dr. Panaccione sees a clear role for oral therapies in the evolving treatment landscape. “This profile combined with using Rinvoq as once-daily oral can make a practical option for patients that need long-term management of the disease.”

The SEQUENCE Study in Crohn’s Disease

If PROFUNDUS addresses the question of whether efficacy observed in trials translates to real-world practice, the SEQUENCE study tackles a different but equally important question: once patients achieve remission, how long can they sustain it?

The SEQUENCE study enrolled patients with moderate to severe Crohn’s disease and prior anti-TNF failure—a population generally considered more refractory to treatment. In Part 2 of the ongoing study, 224 patients who completed the week 48 visit continued on open-label Skyrizi 360 mg subcutaneously every eight weeks. The durability analysis presented at ECCO tracks patients through week 148, representing three years of continuous treatment.

Dr. Laurent Peyrin-Biroulet, who has been involved with the study, finds the consistency of response particularly noteworthy. “The durability of responses from SEQUENCE is notable, with approximately 98% of patients who achieved clinical remission per Crohn’s disease activity index at week 8 maintained it at week 148 in the as-observed analysis, and the data by stool frequency/abdominal pain scores tells a similar story.”

The as-observed analysis shows that among patients who achieved clinical remission at week 8, 98.5% maintained CDAI remission at week 148, while 88.1% maintained remission based on stool frequency and abdominal pain scores. For patients who achieved remission later, at week 48, durability remained high: 94.2% maintained CDAI remission and 87.3% maintained SF/APS remission through week 148.

“That consistency over nearly three years in a population that had all failed prior anti-TNF therapy is noteworthy,” Dr. Peyrin-Biroulet observes. “From a mechanistic standpoint, it supports the hypothesis that selective IL-23 inhibition—targeting the p19 subunit specifically—may address a central driver of the chronic inflammatory cycle in Crohn’s disease in a sustained way, rather than simply suppressing symptoms acutely.”

The endoscopic outcomes reinforce this interpretation. Among patients who achieved endoscopic response at week 24, 84.7% maintained it at week 148. For endoscopic remission, the maintenance rate was 78.2%, and for mucosal healing—the most stringent endpoint requiring complete ulcer resolution—67.3% of early responders maintained healing through three years.

“When working with patients, it is so important to work together to focus on both the short-term and the long-term goals for patients,” Dr. Peyrin-Biroulet emphasizes. “Reaching endoscopic remission is one of the more clinically significant aspects of the SEQUENCE data and a very important long-term outcome.”

He draws attention to the mucosal healing figure specifically. “The mucosal healing figure is particularly worth discussing because it’s the most stringent of these endoscopic endpoints, requiring complete ulcer resolution, and the fact that two-thirds of early achievers maintained it at nearly three years is meaningful.”

The relevance of these findings extends to how clinicians approach treatment goals. “These findings reinforce the growing consensus in the IBD community that we should be treating beyond short-term symptom relief and aiming for objective mucosal targets,” Dr. Peyrin-Biroulet explains. “Symptom resolution and endoscopic healing don’t always align, and patients can see improvement in their symptoms while mucosal inflammation is still ongoing within the gut lining.”

The SEQUENCE population’s prior treatment failure makes the durability data particularly relevant for positioning Skyrizi in the treatment algorithm. “The SEQUENCE study is particularly relevant to treatment positioning because the entire population had prior anti-TNF failure—a group that has historically been considered harder to treat,” Dr. Peyrin-Biroulet notes. “The fact that durable clinical and endoscopic responses were maintained through week 148 in this population adds to the body of evidence supporting Skyrizi as an effective option in the biologic-experienced setting.”

Looking ahead, he sees selective IL-23 inhibition playing an expanding role. “Looking ahead, I think selective IL-23 inhibition will continue to play an important role across the treatment algorithm as an earlier treatment option and as we get better at identifying the patients that are most likely to respond to which mechanism.”

The APPRISE Study

Complementing the long-term controlled data from SEQUENCE, the APPRISE study provides real-world confirmation of Skyrizi’s effectiveness in routine clinical practice. This ongoing global prospective observational study enrolled the first 500 patients with Crohn’s disease who initiated Skyrizi according to local prescribing patterns.

The 6-month interim analysis shows that 84.1% of patients who achieved clinical remission at 3 months sustained that remission at 6 months. Corticosteroid-free clinical remission at 3 months was achieved by 60.3% of patients, with 82.5% of those maintaining steroid-free remission at 6 months.

Particularly striking are the outcomes among patients with prior ustekinumab failure—a group that poses clinical challenges given the shared IL-23 pathway targeting. Among these patients, 95.5% achieved clinical remission at both 3 and 6 months, and approximately 60% achieved corticosteroid-free remission at 3 months regardless of prior advanced therapy exposure.

The safety profile in this real-world cohort mirrors that observed in clinical trials: 41.6% of patients reported any treatment-emergent adverse event, 8.9% reported serious adverse events, and 2.9% discontinued Skyrizi treatment. One death occurred after the 6-month data cutoff and was determined unrelated to treatment.

Endoscopic Healing Predicts Better Outcomes

The U-ENDURE long-term extension study adds another dimension to the growing body of evidence supporting early achievement of endoscopic targets. Among 244 patients with moderate to severe Crohn’s disease receiving Rinvoq maintenance treatment, those who achieved endoscopic response, endoscopic remission, or ulcer-free endoscopy at week 52 experienced significantly better outcomes through week 96.

Patients with endoscopic remission at week 52 achieved substantially higher rates of CDAI remission (65.2% vs 47.0%), IBDQ remission (62.5% vs 39.4%), and FACIT-F response (46.4% vs 29.5%) at week 96 compared to those who did not achieve endoscopic remission. Perhaps most clinically meaningful, CD-related hospitalizations or surgeries occurred in only 2.7% of patients with endoscopic remission versus 7.6% of those without—an incidence rate of 0.01 versus 0.04 per patient-year.

The relationship held across all endoscopic outcome measures, with ulcer-free endoscopy showing the strongest associations with subsequent clinical and patient-reported outcomes.

The Evolving Treatment Landscape

Stepping back from individual studies, both investigators see a field in transformation. The combination of long-term durability data from controlled trials and confirmation of effectiveness in real-world populations provides clinicians with greater confidence in treatment selection.

Dr. Panaccione emphasizes the practical implications: “Management of ulcerative colitis is never just about short-term symptom control but also looking at the long-term management of the disease. We’re also aiming for mucosal healing, in other words deeper healing that raises the bar from feeling better to being better at a tissue level, and we need to monitor patients carefully over time.”

Dr. Peyrin-Biroulet synthesizes the broader implications: “These findings overall reinforce what the IBD community increasingly recognizes, that treatment must go beyond symptom relief and target deep healing at a mucosal level. This matters because patients can feel better while active inflammation still persists beneath the surface, silently driving disease progression.”

As the ECCO Congress unfolds in Stockholm, the data presentations will undoubtedly generate discussion about optimal positioning of these therapies, sequencing strategies, and how to identify which patients benefit most from which mechanism of action. But for clinicians in daily practice, the message is becoming clearer: durable remission is an achievable goal for more patients than ever before, and the evidence supporting that goal continues to accumulate across both controlled trials and real-world settings.