Raymond Cross, MD, on Risk Stratification and Individualized Treatment Selection in Evolving IBD Management

Raymond K. Cross, MD, MS, FACG, AGAF, outlined a framework for tailoring treatment based on patient characteristics, disease behavior, and emerging prognostic tools in a session on personalized therapy in inflammatory bowel disease (IBD) at the Advances in IBD annual meeting.

Dr Cross is the Medical Director of The Center for Inflammatory Bowel and Colorectal Diseases at Mercy Medical Center in Baltimore, Maryland.

He defined the overarching goals of IBD therapy: inducing clinical remission, avoiding short- and long-term toxicity, maintaining steroid-free remission, and reducing unnecessary health care utilization. These targets guide the central principle of personalized care: "select the right drug, for the right patient, at the right time.” Dr Cross noted that precision medicine “takes into account individual variability in genes, environment, and lifestyle,” and aims to move beyond a one-size-fits-all approach.

Treatment selection requires a deliberate assessment of patient and system factors. Disease, age, reproductive considerations, prior biologic exposure, adherence patterns, preferences for oral, intravenous, or subcutaneous therapy, and logistical issues such as proximity to infusion centers all influence management decisions, Dr Cross explained. Additional considerations include costs of therapy and monitoring, insurance formulary constraints, needle phobia, comorbidities, and access to support programs. Healthcare team resources, including the ability to monitor response, optimize therapy, and engage clinical trials, further shape treatment pathways.

Risk characterization remains central to determining when to initiate advanced therapy. For Crohn’s disease, Dr Cross highlighted predictors of worse outcomes, including large or deep ulcers, fistulas or abscesses, ileal or upper gastrointestinal involvement, extensive disease, cigarette smoking, perianal disease, NOD2 mutation, and multiple positive serologies. Using these factors, the American Gastroenterological Association clinical pathway stratifies patients into low- and high-risk groups. Low-risk patients typically present with limited involvement, superficial ulcerations, non-penetrating disease, and diagnosis after age 30. High-risk patients show extensive involvement, deep ulcers, perianal or rectal disease, prior resection, younger age at diagnosis, and complicated behavior, Dr Cross stated.

Emerging data support early intervention for patients with moderate to severe Crohn’s disease. Dr Cross referenced the PROFILE study evaluating infliximab and immunomodulators in newly diagnosed patients, noting that enrollment occurred early after diagnosis. The trial also explored a prognostic biomarker, underscoring the growing interest in integrating molecular predictors into therapeutic decision-making.

In ulcerative colitis, predictors of a worse course include extensive involvement, deep ulcers, hospitalization, steroid need, concomitant infections, and immune-mediated diseases. Dr Cross noted that tools such as the ED presentation score, in which tachycardia and hypoalbuminemia predicted complex hospitalization, and the ACE score, to detect hypoalbuminemia, elevated CRP, and increased endoscopic severity, help identify patients at risk for complex hospitalization, early need for second-line therapy, or surgery.

Dr Cross emphasized that “predictors of a moderate to severe disease course or moderate to severe disease activity warrant starting an advanced therapy.” Conversely, clinicians should use clinical history and diagnostics to identify the smaller subset of Crohn’s disease patients with mild disease who may not require advanced therapy. He cautioned against withholding effective treatments in patients with comorbidities, frailty, or advanced age, noting that steroids and active inflammation remain the dominant risk factors for adverse outcomes.

Looking ahead, Dr Cross described a future in which decision support tools are integrated into electronic records and predictive models leverage genetics and multiomic data. For practicing gastroenterologists, the session reinforced the importance of early risk assessment, individualized treatment alignment, and readiness to escalate therapy based on disease behavior rather than demographic assumptions.

Reference
Cross R. Personalized therapy in IBD (current and future state). Presented at: 2025 AIBD Annual Meeting. December 8-10, 2025.