Florian Rieder, MD, Reviews Therapeutic Management of Crohn Disease

Earlier is better for any and all therapies in the management of Crohn disease (CD) among adults, Florian Rieder, MD, noted during his presentation at the Advances in Inflammatory Bowel Disease virtual meeting held on April 20-April 21. He also stressed on the treat-to-target approach and modified diet as therapy recommendations.

Dr Rieder, MD, is vice-chair and codirector of the inflammatory bowel disease (IBD) section, and director of the Advanced IBD Fellowship program at the Cleveland Clinic in Cleveland, Ohio. His clinical focus is patients with IBD with a special emphasis on pathogenesis, prediction, and therapy of intestinal fibrosis. He received the Sherman Emerging Leader Prize in 2019.

The ultimate goal in the management of CD is the same for patient as well as doctor and that is “restoring normal bowel function and improving overall quality of life,” Dr Rieder stressed during his presentation. “Induce and maintain steroid-free remission over time, and modify the natural history of IBD is the gold standard of any treatment for CD.”

The 2018 American College of Gastroenterology clinical guideline for the management of CD among adults penned by Gary Lichtenstein, MD, et al, published in the American Journal of Gastroenterology, presented an all-encompassing and comprehensive update to diagnose and treat adults with CD.

“Patients who are at high risk for colorectal neoplasia, such as those with a history of dysplasia and those with primary sclerosing cholangitis, should consider use of chromoendoscopy,” Dr Rieder stated. Among individuals with moderate risk factors, high-definition white-light endoscopy would produce the same results as chromoendoscopy for detection of dysplasia.

While vedolizumab and ustekinumab have already been approved and widely used in the treatment of CD, Dr Rieder elaborates on which patients should consider biologic treatment. Dr Rieder said, “20-30% of patients with CD have disease that does not mandate the use of a biologic agent, as the disease may not progress.” According to the new recommendations, health care providers may choose to not treat some low-risk patients with biologics. Instead, they can do routine follow-ups with both cross-sectional imaging and endoscopy to ensure that the disease does not progress.

Depending on the IBD type, location, and disease severity, Dr Rieder noted, combination therapy should be considered as it may lessen immunogenicity and increase trough levels of a biologic agent. “If a patient has a poor prognosis and significant disease activity, it is important to consider the use of combination therapy with a biologic agent and an immunomodulator,” he explained.

Without enough evidence to make a recommendation, nothing new has been established for surgical treatment of CD. The presence of an abdominal abscess still warrants for the consideration of surgery. However, some patients may skip the surgical process by opting for medical therapy after drainage guided by radiology. “Surgery would still be required for patients who have complications of disease, such as intractable hemorrhage, perforation, obstruction, abscess, dysplasia, cancer, or disease that is medically refractory,” Dr Rieder noted.

Findings of a randomized controlled trial of 74 patients (mean age 14.2 years) have suggested that CD exclusion diet in conjunction with partial enteral nutrition may result in sustained remission. While both diets (partial and entire enteral nutrition) successfully induced remission by week 6, partial enteral nutrition was generally better tolerated among children than entire enteral nutrition.

Another study looking into the role of diet in achieving sustained remission in CD compared the effectiveness of the specific carbohydrate diet to the Mediterranean diet. Out of 191 patients randomly assigned to both diets for 12 weeks, “the percentage of participants who achieved symptomatic remission at week 6 was not superior with the specific carbohydrate diet (46.5%; MD, 43.5%; P = .77)” Taking the ease of following a Mediterranean diet and its benefits into consideration, the authors preferred Mediterranean diet to a specific carbohydrate diet for most patients with mild to moderate CD.

The SEAVUE trial provided better insight into the effectiveness of ustekinumab versus adalimumab for induction and maintenance therapy among biologic-naïve patients. From the randomly enrolled group, 191 patients received ustekinumab and 195 received adalimumab for 52 weeks. At week 52, 124 (65%) of the ustekinumab group versus 119 (61%) of the adalimumab group were in clinical remission. Some infections were reported—3% in the adalimumab group and 2% in the ustekinumab group, but no deaths occurred throughout the length of the study.

Another meta-analysis comparing the effectiveness of ustekinumab and vedolizumab among patients with CD with prior anti-TNF failure revealed ustekinumab to be more effective than vedolizumab as maintenance therapy. Both the drugs, however, were just as effective in induction.

Within the purview of adalimumab, does the dosing matter? The SERENE CD trial sought to evaluate whether a high-dose adalimumab was more effective in achieving clinical remission than a standard-dose. The phase 3, randomized, double-blind, multicenter trial followed 308 patients at higher dose and 206 patients at standard dose. Between the two groups, similar proportions of patients achieved clinical remission at week 4 (44% in both; P = .939), and endoscopic response at week 12 (43% high-dose vs 39% standard-dose, P = .462) thus proving, that there is no need to subject patients to higher doses in expectation of better results.

Among 542 patients enrolled in the FORTIFY trial, 74 (52%) of patients in the risankizumab group achieved clinical remission vs 67 (41%) in the placebo group. Similarly, stool frequency and abdominal pain score clinical remission was reached in 73 (52%) of the risankizumab group vs 65 (40%) of the placebo group; and endoscopic remission, too, was reached in 66 (47%) of the risankizumab group vs 36 (22%) of the placebo group. The findings may open doors to a new and safe therapeutic option for maintenance of remission in patients with moderately to severely active CD.

In the absence of specific therapeutic biomarkers, Dr Rieder said, “employ treat-to-target strategies.”

In summary, regardless of the therapy, Dr Rieder urges to be mindful of patient factors such as age, fertility, patient preferences, costs of treatment and monitoring; not to forget healthcare and system factors such as Medicare and Medicaid, ease of access to health care, insurance restrictions, and access to clinical trials.

—Priyam Vora

Reference:
Rieder F. Update on the Management of Crohn’s Disease. Presented at: Advances in Inflammatory Bowel Disease virtual meeting. April 20-21.