Q&A: Managing IBD in Special Populations

With global obesity rates and the incidence of inflammatory bowel disease (IBD) continuing to rise, clinicians must increasingly address the care of complex patients who present with Crohn disease and ulcerative colitis. Patients with IBD who also are obese, are older, or are or want to become pregnant, require careful attention to therapeutic agent selection, dosing, counseling, and lifestyle modifications to reduce complications and achieve mucosal healing.

Cynthia Seow, MBBS, and Sherman Picardo, MBBS, from the Inflammatory Bowel Disease Centre at the University of Calgary in Alberta, Canada, and Siddharth Singh, MD, MS from the Division of Gastroenterology at the University of California at San Diego, recently discussed the issue of treating special populations with Gastroenterology Consultant, following publication of their research¹ on this topic.

GASTRO CON: Your study mentioned that one-third of patients with IBD are obese. How does obesity complicate the treatment of IBD? What additional risks and challenges do these patients and their physicians face, and how can they address these issues?
Cynthia Seow, Sherman Picardo, and Siddharth Singh: Obesity is associated with greater difficulty in achieving remission, a high risk of disease relapse, and high burden and costs of hospitalization in patients with IBD. Obese patients also have an inferior response to biologic therapy related to altered pharmacokinetics and obesity-related chronic inflammation. This may be related to impaired absorption of subcutaneously administered agents, rapid proteolysis, and to a “TNF-sink” phenomenon with higher inflammatory burden because of the excess adipose tissue.

Surgical management of this cohort is also technically challenging and associated with longer operative times, an increased likelihood of conversion to open procedures, and higher rates of postoperative complications—wound infections in particular. Physicians may want to consider weight-based rather than fixed-dose regimens or oral targeted small molecule inhibitors with careful monitoring of disease activity in individuals with obesity. We eagerly await further research on adjunctive therapy for obesity, including diet and/or lifestyle-induced weight loss or pharmacologic therapies, in the setting of IBD.

GASTRO CON: You also note that in the next decade about one-third of patients with IBD will be older than 60 years of age. How does a patient’s age affect their response to IBD therapies, and how can gastroenterologists prepare for increasingly seeing older patients with this disease?
CS, SP, SS: Older age increases susceptibility to immune-mediated diseases, in addition to changes in the gastrointestinal tract as a result of dietary shifts, alterations in gastrointestinal motility, increased intestinal permeability, and changes in the gut microbiota that might influence host-inflammatory responses. There is a higher prevalence of other gastrointestinal disorders that can mimic IBD in this cohort, but physicians should still have a low threshold for investigating these patients for IBD, given the risks of morbidity and mortality that can result from untreated disease or disease-related complications.

Although mucosal healing is the recommended target for individuals with IBD, treatment targets and goals need to be flexible and dynamic in older patients, given their increased susceptibility to treatment related and extraintestinal complications. Clinicians should exercise particular caution in using corticosteroids in this population, in view of these patients’ higher risk of serious infections, susceptibility to short-term adverse effects such as insomnia, mood instability, and delirium, and long-term effects, including osteoporosis, pathologic fractures, hyperglycemia, and cataracts.

Immunomodulator therapies—namely thiopurines—may also increase susceptibility to serious infections and malignancy, specifically lymphoma and nonmelanoma skin cancers. Likewise, exposure to biologics has been associated with an increased risk of serious infections in older patients.

There are limited data on the safety of non-TNF-targeted biologic agents in this cohort. Biologic monotherapy may be considered over combination biologic and antimetabolite therapy due to the potential for treatment-related complications. Ultimately, management of older individuals warrants careful consideration of the risks of disease-related vs treatment-related complications, in the context of individual values, preferences, functional status, and comorbidities.

GASTRO CON: Patients with IBD who are or who want to become pregnant also present special challenges. What concerns must be addressed when designing a treatment regimen for a patient with IBD before and during pregnancy, and then when breastfeeding? 
CS, SP, SS: The goal of tight disease control for women contemplating pregnancy or who are pregnant is similar to that of any individual with IBD. Importantly, caring for these patients requires a proactive, multidisciplinary approach. Since more than 25% of women with IBD conceive for the first time after being diagnosed, it is imperative for the practitioner to be conversant with preconception, intrapartum, and postpartum counseling. This includes the effect of IBD on pregnancy, the effect of pregnancy on IBD, the effect of medications during pregnancy and breastfeeding, mode of delivery, and preventive care (including nutrition, cervical cancer screening, and vaccinations). Comprehensive counseling is associated with significant improvements in patients’ adherence to IBD medications and a reduction in disease relapse during pregnancy.

Active disease can result in potential adverse outcomes for both mother and neonate, including higher risks of preterm birth, low birth weight, miscarriage, and stillbirth. Therefore, practitioners should undertake a comprehensive disease assessment and appropriate disease optimization to ensure disease stability for at least 6 months prior to the patient conceiving. IBD therapies (with the exceptions of methotrexate and tofacitinib) are considered both safe and efficacious during pregnancy and breastfeeding. Clinicians should strive to reassure patients who are pregnant or who are considering pregnancy that these medications do not present teratogenic or infection risks.

Specifically, physicians should emphasize that increased risk of infection in the infant related to preterm birth, which can result from underlying maternal disease activity, exceeds the infection risk related to the IBD medications. Based on current data, the choice of therapy should be tailored to what best suits the mother, taking into account disease severity and response to prior therapies, though ongoing drug surveillance and reporting are necessary to reassure mothers regarding the safety of newer therapeutic agents.

GASTRO CON: Some patients will present with 2 of these conditions simultaneously: for example, some obese patients will be older than 60 years, and some patients of childbearing age will be obese. What advice do you have for gastroenterologists who may be treating these patients?
CS, SP, SS: Regardless of an individual’s age, weight, gender, comorbidities, or family planning wishes, regular objective disease monitoring of IBD is essential. Beyond clinical assessment, this includes laboratory and stool testing (fecal calprotectin), as well as endoscopic and radiologic/sonographic evaluation. This provides the physician and patient timely opportunities to optimize therapy with the goal of achieving mucosal healing, which has been associated with a reduction in long-term IBD complications. Patients should be frequently reminded that the risk of active disease significantly outweighs the risk of active treatments, and that current therapies have an increasingly favorable adverse event profile.

GASTRO CON: What are the key takeaway messages of your research?
CS, SP, SS: Practitioners should recognize that the epidemiology of IBD is progressively evolving, as are the types of patients that we will be seeing in our everyday practice. While this may be challenging, the goals of care remain unchanged—achieving and maintaining mucosal healing to minimize long-term complications and enhance the quality of life for these patients through clear patient-centric counseling and the provision of safe and effective therapies.

 Reference:

1. Singh S, Picardo S, Seow CH. Management of inflammatory bowel diseases in special populations: obese, old, or obstetric. Clin Gastroenterol Hepatol. 2020;18(6):1367-1380. https://doi.org/10.1016/j.cgh.2019.11.009

Cynthia Seow, MBBS, FRACP, is associate professor of medicine in the Inflammatory Bowel Disease Centre at the University of Calgary in Alberta, Canada.

Sherman Picardo, MBBS, FRACP, trained at the Inflammatory Bowel Disease Centre at the University of Calgary in Alberta, Canada, and is now a Staff Gastroenterologist at Royal Perth Hospital, Perth, Western Australia.

Siddharth Singh, MD, MS, is assistant professor of medicine in the Division of Gastroenterology at the University of California at San Diego.