Treat-to-Target to Proactively Manage IBD

In developing an effective plan for disease monitoring for all patients with inflammatory bowel diseases (IBD), a treat-to-target clinical management strategy can mitigate the risk of recurrence and complications, David T. Rubin, MD, stressed in his presentation at the Advances in Inflammatory Bowel Disease Regionals meeting in Chicago, Illinois, July 23.

Dr Rubin is the Joseph B. Kirsner professor of medicine, professor of pathology, and chief of the Gastroenterology, Hepatology, and Nutrition division at the University of Chicago.

“The ultimate goal of IBD management is to change the natural history of IBD – to avoid hospitalization and surgery, to avoid drug-related and disease-related complications and to reduce the cost of care,” said Dr. Rubin, a world-renowned expert on the treatment and research of IBD. To do so effectively, it is imperative to clarify the disease type and severity for each patient and to identify the extraintestinal manifestations, which may include pain, fatigue, mental health, or sexual dysfunction, he explained.

Remission, Dr Rubin stated, is “sustained functional remission; a meaningful functional remission that lasts.” Unfortunately, he said, despite best efforts, there is a vast difference of opinion in disease management goals between patients and clinicians.

A 2019 survey to evaluate experiences and perceptions of patients with CD or UC and their physicians revealed that while there were some similarities in treatment goals and communication needs, many differences existed in how each group defined remission and in their expectations of treatment duration. Patients defined remission based on symptoms; physicians defined remission based primarily on clinical tests, Dr Rubin said. Patients expected current treatments to control their disease for a longer duration than the physicians did. Bridging the gap of information and expectations through education and communication would benefit patients multifold, he stated.

Dr Rubin pointed out that patient symptoms may have no correlation with endoscopic and mucosal inflammation. However, studies have found a correlation between C-reactive protein (CRP) levels and the Crohn disease activity index (CDAI). Understanding the factors that increase CRP levels among patients with CD may be important in predicting moderate and severe disease activity.

Research has shown that selecting therapeutic targets in IBD helps in clearly defining treatment strategies. STRIDE 2 confirms that the most important long-term, achievable treatment targets among patients with IBD are clinical remission, restoration of quality of life, and absence of disability. With adjustments in therapy, even when no mucosal or histological healing is observed[RM1] , “real-world treat to target is possible.”

Dr Rubin reviewed the comparison of a treat-to-target approach with conventional Crohn disease management in the Randomized Evaluation of an Algorithm for Moderate to Severe Crohn’s Treatment (REACT) study. In the 24-month program, patients who received early combined immunosuppression achieved significantly higher rates of symptomatic remission than patients who received conventional treatment (76% vs 62%). The early immunosuppression group also had a lower rate of hospitalization, complications, or surgery (27.4%) than patients being conventionally managed (34.7%).

In the multicenter, randomized controlled study CALM, patients treated to target consistently achieved superior endoscopic and deep remission outcomes. Dr Rubin noted that 45.5% of the treat to target group achieved the primary endpoint of a Crohn Disease Endoscopic Index of Severity score (CDEIS) of ≤4 and no deep ulcerations, while 30.3% of patients in the clinical management group reached the endpoint. In the  STARDUST trial, the primary endpoint of Simple Endoscopic Score for Crohn Disease (SES-CD) improved ≥50% (95% CI) at Week 48 among patients treated to target. Dr Rubin also recommended the use of VERDICT, a randomized controlled trial to determine optimal treatment target in active UC.

Dr Rubin repeatedly stressed on the importance of disease monitoring during both active and quiescent phases of IBD. Using biomarkers such as CRP and hemoglobin; stool markers, including fecal calprotectin or lactoferrin; endoscopy; and radiology, including computer tomography enterography (CTE), magnetic resonance elastography (MTE) or intestinal ultrasound (IUS), proactive disease monitoring can detect subclinical relapse before the onset of symptoms.

In its traditional approach, IBD management poses several challenges: lack of predictive therapeutic biomarkers, large secondary loss of responses, assumption that induction dictates maintenance in all patients, the disease changing over time, or the patient changing over time. Strategies to overcome these challenges include optimizing treatment, personalizing care, optimizing therapeutics, sequencing wisely, and using proactive management.

“Treating to a target is the way to personalize therapy,” explained Dr Rubin. The primary goal, for both patients and clinicians, is to maximize health-related quality of life. This could manifest either in control of symptoms, or increasing normal functional and social participation, or both. He stressed the need for “systematic assessment of an identified target and serial adjustment of therapy until the target is reached or until the patient refuses or we run out of options.”

Dr Rubin laid out a step-by-step plan to treat-to-target in the absence of specific therapeutic biomarkers. It starts with assessing the disease activity and severity, which helps in establishing targets that correlate with endoscopy. Engaging in a shared decision-making process with the patient to choose individual therapy helps to establish clear goals of therapy while considering individual risk factors. Early assessment should take place no more than 6 weeks following the initiation of treatment. This helps in determining if the patient is adherent to the therapy, if dose adjustment is needed, and if additions or changes need to be made to the selected therapy. Subsequently, clinicians should reassess target at regular intervals, which may vary, for disease monitoring.

In conclusion, Dr Rubin said that if improved quality of life is the primary goal, then adopting a treat-to-target strategy will help in communication and negotiation with the patients. Conventional management of CD and UC has heavily relied on reactive treatment driven by symptoms alone. However, a treat-to-target approach may help in getting ahead of the problem by addressing underlying inflammation, minimizing disease activity at the early stages of disease development, limiting progression, and in turn, improving long-term outcomes.

Even though “the timing of assessments and optimization of therapy may vary by drug and disease type,” Dr Rubin said, “we want patients to feel perfect, and for it to last forever.”

—Priyam Vora

Reference:
Rubin D. Treating to Target: Where Are We Today? Presented at: Advances in Inflammatory Bowel Disease Regionals; July 23, 2022. Chicago, IL