Optimizing IBD Treatment and Sequencing, With Jordan Axelrad, MD, MPH

With a growing number of mechanisms of action now available for Crohn's disease and ulcerative colitis (UC), choosing a first-line therapy and sequencing treatment after failure has become a more layered decision. For Jordan Axelrad, MD, MPH, co-director of NYU Langone's Inflammatory Bowel Disease Center, that decision starts with disease activity and severity, and ends with the patient at the table.

"Once we sort of meet in the middle of what's important to the patient and how severe and active their disease is, which also influences drug selection, then we make a decision together," Axelrad told HCPLive in an interview.

Assessing Activity, Severity, and Patient Preference First

Every new patient visit begins with 2 assessments, Axelrad said: disease activity, a snapshot of what is happening right now, and disease severity, meaning the patient's risk of disease progression and long-term prognosis. The latter is especially relevant in Crohn's disease, though it factors into UC management as well.

Alongside that clinical picture, Axelrad brings the patient into the decision directly, gauging what matters most to them: whether they can accommodate an infusion, whether they are willing to self-inject, or whether they want to stay on an oral medication. Drug selection ultimately reflects where disease severity and patient preference meet.

Sequencing Therapy After Failure

That same framework carries forward once a first therapy fails. After confirming failure objectively, through biomarkers or endoscopy rather than symptoms alone, Axelrad typically moves to therapies with evidence in the second or third-line setting, primarily anti-TNF agents and JAK inhibitors today. Disease activity and severity remain the deciding factors in what a patient needs next.

Treat-to-Target and Confirming True Remission

Underlying all of this is a treat-to-target approach that Axelrad discusses with every patient starting therapy, so that expectations are aligned from day one. "I'm having that conversation with patients so they can understand exactly the expectations of when they may start feeling better," Axelrad said. Patients are told what to expect and when: symptomatic improvement within a couple of weeks to months, biomarker improvement on a similar timeline, and longer-term endoscopic, or in Crohn's disease sometimes radiographic, improvement as the ultimate target.

Meaningful endoscopic response is generally expected within 6 months to 1 year, and treatment is adjusted when that goal is not met. Response is not uniform. Some patients show no benefit from a given therapy and require a switch to a different mechanism entirely, while others have a partial response that can be optimized within the same drug to reach treat-to-target goals.

Evaluating Where New Therapies Fit

That framework also shapes how Axelrad evaluates new therapies as they reach the market. Despite the expanding treatment landscape, he pointed to a persistent, substantial amount of unmet need in IBD. "A meaningful disease remission as far as endoscopic remission is difficult to achieve with our current therapeutic arsenal," Axelrad said, noting that certain Crohn's disease subtypes, such as fistulizing and stricturing disease, respond far less well to existing therapies than others.

When a new drug comes to market, Axelrad said the central question is where its value lies. "Is it a route of administration? Is it a safety? Is it efficacy? Does it work in unique subtypes? Where is that value?" he said. Therapies that work well in patients who have already failed other treatments are especially valuable additions, since that population carries the greatest unmet need. Even with continued approvals, Axelrad said the field is still searching for new therapies, or combinations of therapies, that move more patients toward meaningful, lasting disease control.

References

1. National Institute of Diabetes and Digestive and Kidney Diseases. Crohn's disease. NIDDK. Reviewed July 2024. Accessed August 18, 2026. https://www.niddk.nih.gov/health-information/digestive-diseases/crohns-disease

2. Crohn's & Colitis Foundation. What are the early indicators of Crohn's disease and ulcerative colitis, and how are these two diseases different from each other? Crohn's & Colitis Foundation. Accessed August 18, 2026. https://www.crohnscolitisfoundation.org/blog/ulcerative-colitis-vs-crohns-disease-what-are-the-early-signs-and-how-are-they-diagnosed