Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, relapsing inflammatory condition of the gastrointestinal tract associated with a growing global health burden. Patients with IBD are known to have distressing and severe physical symptoms such as abdominal pain, diarrhea, fecal urgency, fatigue, weight loss, and rectal bleeding. This can be debilitating, profoundly impacting a person’s social life and mental well-being.
Although the precise cause of IBD remains unclear, it is widely understood to arise from a complex interplay of genetic susceptibility, intestinal barrier dysfunction, microbial imbalance, dysregulated immune responses, and environmental factors. This heterogeneity is reflected in treatment response, where no single therapeutic approach is universally effective.
New data presented at Digestive Disease Week (DDW) 2026 highlight a persistent need for long-term disease control, while also pointing to emerging strategies that may help address refractory disease.
Real-world evidence highlights persistent cycles of disease activity
Despite advances in biologic and targeted therapies, real-world data presented at DDW 2026 suggest that many patients with IBD continue to experience recurrent periods of poor disease control.
“This study examined real-world patterns of suboptimal treatment in patients with CD and UC, with the aim of better understanding the gap between what is clinically achievable and what patients are actually receiving in routine care,” David Rubin, gastroenterologist at the University of Chicago and lead author of the study, told DDN.
Using US insurance claims data between 2017 and 2024, researchers assessed disease activity using a composite definition of “suboptimal control,” including treatment escalation or switching, initiation of advanced therapies, corticosteroid use, emergency department visits, hospitalizations, or IBD-related surgery.
The analysis showed that patients frequently cycle through episodes of instability and intervention rather than achieving sustained remission. Approximately one in three patients with CD and one in five with UC experienced multiple episodes of suboptimal control over follow-up. Overall, around a quarter of total follow-up time was spent in a state of active or poorly controlled disease.
This pattern reflects a broader limitation in current IBD management. Despite recent advances in understanding the pathogenesis of IBD and the expansion of targeted therapies, approximately one-third of patients do not respond to their first treatment, and roughly half eventually lose response over time.
“And so, it implies very importantly that we must do better,” said Rubin. He argued that the key takeaway for IBD management in 2026 is the importance of treating early and effectively. At the point of diagnosis of CD or UC, selecting an appropriate advanced therapy that matches disease severity and patient need can help achieve rapid remission. This in turn reduces the risk of loss of response, emergency department visits, hospitalizations, unnecessary surgery, and corticosteroid exposure.
While treating early is critical, treating effectively can be harder. IBD is an incredibly heterogeneous disease, making it difficult to predict which therapy will work best for a given individual and contributes to trial-and-error prescribing in routine care. More detailed molecular and cellular profiling could enable more rational therapy selection and support a more personalized approach to IBD management.
Rubin emphasized, however, that imperfect prediction should not delay decisive treatment. “The nuance of having a perfect therapeutic biomarker is outweighed by the practical reality that most of our current therapies will work early in most patients,” he said.
Expanding treatment goals beyond symptom control
In a disease as heterogeneous as IBD, how disease activity is defined and measured is also a central issue in understanding and managing treatment response. Traditionally, treatment success in IBD has been defined by symptom improvement. However, patients may still experience ongoing intestinal damage even in the absence of symptoms, as current therapies generally only slow disease progression rather than stop it.
As Kori Wallace, Vice President, Global Head Immunology Clinical Development at AbbVie, told DDN, “Symptoms do not correlate to endoscopy. The gold standard of what is going on in the patient happens in the gut,” she said. “You can have patients who feel great, and you go in and scope them, and it’s a mess inside.”
This has driven a shift toward more objective measures of disease activity, including endoscopic and biomarker-based assessment. “The gold standard and where all the treatment guidelines and treatment algorithms focus is to heal the mucosa, heal the gut,” said Wallace.
Mucosal healing, defined as the absence of visible inflammatory ulceration and restoration of normal mucosal architecture, is now a key therapeutic target. One of the most promising strategies to heal the mucosa focuses on directly interrupting the immune signaling pathways that drive intestinal inflammation, with the goal of achieving deeper and more sustained disease control.
Dual pathway inhibition offers a new strategy for refractory disease
A new investigational therapy developed by Johnson & Johnson was also presented at DDW 2026, targeting two key immune signaling pathways involved in the inflammatory cascade of IBD. The Phase 2b data evaluated JNJ-4804, a co-antibody designed to simultaneously target interleukin-23 (IL-23) and tumor necrosis factor-alpha (TNF-alpha) in patients with moderate-to-severe CD or UC who have already failed at least one prior therapy.
"Currently in IBD treatment each successive therapy produces diminishing returns, and patients who have failed multiple treatments have very limited options," Bruce Sands, immunologist at the Icahn School of Medicine, and lead author of the Crohn's disease study, said in the press release. "By combining two mechanisms of action, we're seeing efficacy that appears to be additive — without increasing safety risk."
The rationale for this approach is based on the complexity and redundancy of immune signaling pathways in IBD. While single agents targeting TNF or IL-23 have improved outcomes for many patients, blocking a single mechanism is often insufficient for sustained disease control.
“In some patients, the immune system essentially finds a way around single therapies,” said Maria Abreu, Executive Director of the F. Widjaja IBD Institute at Cedars-Sinai and lead author of the UC study. “By targeting two pathways at once, we may be able to ‘outsmart’ the immune system and achieve better outcomes.”
In both the DUET-Crohn’s and DUET-UC studies, JNJ-4804 demonstrated higher rates of clinical remission and endoscopic response compared with both monotherapies and placebo. Importantly, the most pronounced effects were seen in patients who had failed two or more prior therapies, where clinical and endoscopic improvements were more substantial than in the overall study population.
However, the trials did not consistently meet primary endpoints across all enrolled patients, underscoring the heterogeneity of response even within more advanced treatment regimens.
Bridging innovation with persistent unmet need
Despite major advancements in therapeutic options over the past decade, the findings presented at DDW 2026 reinforce that there is still a significant gap between current therapies and long-term remission. Real-world data continue to show that many patients cycle through periods of treatment escalation, loss of response, and active disease, rather than achieving durable remission.
While new strategies may improve outcomes for some patients, they also highlight the limits of a one-size-fits-all approach to IBD treatment. Durable disease control will likely depend on pairing therapeutic innovation with better tools for patient stratification, earlier intervention, and more objective assessment of disease activity. Without a clearer understanding of which pathways are driving inflammation in individual patients, treatment selection will continue to rely heavily on trial-and-error sequencing.
Closing this gap will require a more integrated approach to IBD management — one that combines novel treatment modalities with improved molecular profiling, biomarker development, and real-world monitoring. Only by aligning the right therapy with the right patient at the right time can the field move closer to sustained remission as a realistic goal for a broader proportion of people living with IBD.
