DAY 1 - Getting It Right the First Time: Choosing the Optimal Treatment Option for Your IBD Patient

"How would you choose the best therapy for a patient with inflammatory bowel disease (IBD) in 2024?" Asked Dr. Siddharth Singh, Associate Professor of Medicine at the University of California San Diego, during his presentation at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania.

Dr. Singh delivered an insightful presentation on choosing the optimal treatment for patients with IBD in 2024. The talk was prompted by a case study presented by past ACG president, Dr. John W. Popp, involving a patient with multiple comorbidities and Crohn's disease. The case in question involved a patient with a history of diabetes, hypertension, Chronic Obstructive Pulmonary Disease, and Crohn's disease. Over the past decade, the patient had been treated with mesalamine and prednisone. However, in the current year, the patient presented with progressive watery diarrhea, moderate abdominal pain, and mild weight loss. A colonoscopy revealed severely active Crohn's ileocolitis. While the patient showed improvement with prednisone, attempts to taper off the medication resulted in disease flares.

Dr. Singh's presentation focused on how to select the best treatment option for such a complex patient with IBD. He emphasized the importance of understanding the patient's risk of disease complications and treatment complications when making treatment decisions. The conceptual model for treatment decisions, as presented by Dr. Singh, highlighted the goal of achieving sustained remission while minimizing disease complications and avoiding treatment-related complications and disability.

Dr. Singh noted that the rapid development of new IBD medications has significantly improved treatment options available to clinicians and patients. He presented the comparative efficacy landscape, positioning of current therapies, and various clinical trials, focusing on non-TNF medications approved over the last decade. These included ustekinumab, which was initially approved for arthritis and was soon to be approved for Crohn's disease. Other medications discussed were inhibitors like adalimumab and certolizumab, with adalimumab being approved for both ulcerative colitis and Crohn's disease.

Dr. Singh’s talk focused on the effectiveness of Crohn’s disease medications, with an emphasis on head-to-head trials and network meta-analysis. He discussed the SEAVUE trial, which compared ustekinumab and adalimumab in biologic-naive patients and found no significant difference in remission rates. He also highlighted the SEQUENCE trial, which showed ustekinumab as non-inferior and even superior to adalimumab in achieving clinical and endoscopic outcomes. Additionally, he explained the role of network meta-analysis in synthesizing trial data, referencing a 2021 analysis that ranked ustekinumab as the best treatment for biologic-naive patients and suggested alternatives like vedolizumab for patients with greater TNF therapy exposure.

An important point emphasized by Dr. Singh was the need to prioritize effectiveness over safety when choosing medications. He stated, "We should (almost) always choose an effective drug over a safer drug." This approach, he argued, is crucial for achieving remission and improving quality of life. Early intervention with the most effective medication was highlighted as critical, as demonstrated in the PROFILE trial.

Current guidelines, as presented by Dr. Singh, suggest using ustekinumab over adalimumab for naive patients and vedolizumab for those with prior exposure to TNF agents. He stressed that the approach to treatment should consider the patient's risk for downstream complications, treatment complications, and personal values and preferences.
The presentation also touched on the potential for personalized therapy and precision medicine in Crohn's disease treatment. Dr. Singh discussed the evolving field of personalized therapy and the advancing science supporting more tailored treatment approaches based on patient-specific factors. There is scope for studying and identifying patients more likely to respond to specific medications. While clinical trials do not allow for dose escalations, real-world practice often includes dose adjustments. Dr. Singh emphasized the importance of therapeutic drug monitoring and dose adjustments to achieve optimal outcomes.

Dr. Singh concluded his talk with several key take-home points:
1. TNF antagonists remain the best option for Crohn's disease and severe ulcerative colitis.
2. Selective IL-23 antagonists may be the go-to medications for Crohn's disease, especially in patients who have previously failed TNF therapy.
3. JAK1 inhibitors are potentially game-changing oral therapies for ulcerative colitis.

He also noted that while the field is moving from a TNF era to a non-TNF era, this shift should be approached with caution. Selective IL-23 antagonists are outperforming their older IL-12/23 counterparts, and JAK inhibitors show promise if their side effects can be mitigated.

The presentation highlighted the need for an updated network meta-analysis to further inform the positioning of newer biologics and small molecules in the treatment of Crohn's disease, considering both biologic-naive and biologic-exposed patients. It also emphasized the importance of engaging with clinicians to address ongoing questions regarding therapeutic drug monitoring, dose escalation, and opportunities for personalized therapy in IBD management.