In the inflammatory bowel disease (IBD) setting, practices for patient care have evolved in step with the coronavirus disease 2019 (COVID-19) pandemic, translating to adaptations in therapeutic strategy. Although the optimal techniques for patient-centered approaches to diagnosing and managing IBD amid COVID-19 are comparatively less opaque now than they were in late February when the first cases of the novel coronavirus were confirmed in the United States,1 efforts to tailor care for the unprecedented circumstances were often characterized by uncertainty, according to Darren N. Seril, MD, PhD.
“When the pandemic first started worldwide and then in this country, our first thought for patients with IBD who are on immunosuppression was, ‘Are they going to be at increased risk for getting this infection because of the immunosuppression?’ The other thought was, ‘If they are at increased risk, what should we be doing with their medicines to provide them the greatest balance of safety in terms of reducing their risk for contracting the infection vs the adverse outcomes that can occur from the disease,” Dr Seril — who directs the Inflammatory Bowel Disease Program at Rutgers Robert Wood Johnson (RWJ) Medical School in New Brunswick, New Jersey — said in an interview with Gastroenterology Advisor.
Considerations for Standard Therapy
Treatment for Crohn disease and ulcerative colitis (UC) commonly includes immunosuppressive or immune modulating therapies. The efficacy of these interventions in controlling chronic inflammation has been well-documented, but so too have their risk for viral infections.2 For example, current evidence has associated treatment with tofacitinib, an immune modulating Janus kinase inhibitor, with an elevated risk for herpes zoster in patients with UC.3
Some experts in the field, including Gionata Fiorino, MD, PhD, of the Humanitas Clinical and Research Center in Milan, Italy, and colleagues, have contended that these agents “can increase the risk of opportunistic infections, but not that of serious infections,” further arguing that this widely recognized risk has already translated to the development of “adequate measures to protect patients.” Such measures are essential to existing “quality standards of care in IBD,” according to Dr Fiorino and colleauges.4
Nevertheless, small molecule agents’ association with a heightened propensity for viral infection would discourage their use as a first-line therapeutic during the COVID-19 outbreak. “In other words, we may want to consider using that drug less than we would in the past in light of the pandemic,” said Dr. Seril, who also serves as an assistant professor of medicine at Rutgers RWJ Medical School.
Concern about whether IBD treatment should continue or change in certain COVID-19-conscious ways was based not only on the immunosuppressive potential of standard therapies, but also on the method of therapeutic delivery for some agents. Infliximab, ustekinumab, and vedolizumab, for example, are delivered via infusion, necessitating patient visits to infusion centers or, alternatively, transition to home infusion or injectable therapy.2
However, in a clinical practice update published on April 10, 2020, the American Gastroenterology Association (AGA) notably recommended against either substitute. Elective switching to injectable therapies was not advised due to data from an earlier study5 that identified a correlation between a therapeutic shift from infliximab to adalimumab and subsequent relapse. The AGA identified the number of “uncontrolled variables” and the “serious risk that a nurse-provider traveling from home to home may become infected and act as a vector to other patients” as the reasons for the organization’s discouragement of this method of treatment facilitation.
In the absence of hard data that could provide insight on the risk-benefit profile of stable continuation of IBD therapy for patients with diagnosed disease compared with “aggressively” reducing treatment, the answer on how to best proceed was initially ambiguous, Dr Seril said.
“Overall, especially in the beginning, there was this uncertainty about how aggressive we should be in terms of the therapies that we use, but I think we came to a kind of consensus as a community that it’s more important to keep the disease under control,” he explained.
Expanded Insight Guides Practice
With the past nearly 12 months of on-the-ground experience has come clearer perspective on managing IBD during a public health crisis of this scale. “We’re of getting more experienced in terms of what’s safe and what’s not safe,” Dr Seril said.
Much of this insight concerns therapeutic choice in a disease that, due to its immune-mediated nature, frequently requires treatment with corticosteroids, immunomodulators, or monoclonal antibodies to induce and maintain clinical and endoscopic remission.3 As healthcare providers in gastroenterology and other specialties round the COVID-19 learning curve, one of the major take home points in IBD care has centered on the administration of corticosteroids, often used for the acute treatment of IBD flares.
“Overall, the use of steroids is probably safe, but if patients are on steroids, we try to reduce their dose as much as possible or even taper them off. Alternatively, if we can use steroids that have less of an immune suppressing effect and that increase the patient’s risk for infections less than say, prednisone, using those types of medicines might be preferred,” said Dr Seril.
Dr Seril also pointed out that maintenance therapy for IBD, which can include biologics like infliximab and immunomodulators like azathioprine, “appears to be safe to use in patients, even in the setting of the pandemic,” is another key observation that has emerged in recent months. Although he acknowledges that the data on the safety of these maintenance therapies during COVID-19 is limited, this additional information has since made providers “more confident that we can continue these medicines, even during the course of the pandemic,” he explained.
Dr Seril added that the decision of whether or not to initiate specific interventions has been guided by considerations of an agent’s mechanism of action. However, therapy selection during the COVID-19 pandemic should not only take into account the mechanism, but also the length of the treatment course.
“We tend to become focused on using our therapies to get the disease under control, and get it into remission, and then to maintain remission, but sometimes we lose focus a little bit in terms of looking for opportunities to deescalate therapy,” Dr Seril said. “These therapies are not completely benign. They do have the potential for side effects, even though in many cases, we use them because the benefits outweigh the potential for risk. The pandemic has reminded us that if we have the opportunity to reduce immune suppressing medicines in a safe manner, we should definitely try to do that.”
In looking back at the COVID-19-specific treatment concerns that have emerged in IBD care over the past year, Dr Seril calls this a “renewed focus” that he hopes “will stick with us even after the pandemic has gotten under control.” Until then, Dr Seril concludes that shared decision making is another critical component for health care providers to consider, and one that should lead to patient-physician conversation, particularly in instances when patients might appear likely to abruptly stop therapy.
“If there’s any question about whether you’d like to reduce your medicines or stop your medicines, don’t make that decision by yourself; do that in discussion with your physician. It might be possible to deescalate therapy or switch an infusion medication to a different location so patients have reduced exposure to other individuals,” Dr Seril concluded.
1. Evidence for limited early spread of COVID-19 within the United States, January-February 2020. Centers for Disease Control and Prevention. June 5, 2020. Accessed December 14, 2020.
2. Rubin DT, Feuerstein JD, Wang AY, Cohen RD. AGA clinical practice update on management of inflammatory bowel disease during the COVID-19 pandemic: expert commentary. Gastroenterology. 2020;159(1):350-357. doi: 10.1053/j.gastro.2020.04.012
3. Winthrop KL, Melmed GY, Vermeire S, et al. Herpes Zoster infection in patients with ulcerative colitis receiving tofacitinib. Inflamm Bowel Dis. 2018;24(10):2258-2265. doi: 10.1093/ibd/izy131
4. Fiorino G,Peyrin-Biroulet L, Danese S. Protecting patients with IBD during the COVID-19 pandemic. Lancet Gastroenterol Hepatol. 2020;5(7):639. doi: 10.1016/S2468-1253(20)30152-7