Management of Infections in the Immunosuppressed Patient With IBD

Inflammatory bowel disease (IBD) is associated with an increased risk of serious opportunistic infection, while age remains an independent factor, Jessica R. Allegretti, MD, said at the at the Advances in Inflammatory Bowel Diseases 2021 virtual meeting on Saturday, March 6, 2021.

Dr Allegretti is associate director of the Crohn's and Colitis Center and director of the Fecal Microbiota Transplant program at Brigham and Women's Hospital in Boston, Massachusetts. 

Her presentation focused on the serious risks involved and the importance of testing and treatment for both opportunistic and serious infections in patients with IBD.

Risks for serious infection include external factors such as immunosuppression therapy, exposure to pathogens, and geographic clustering, while those inherent to the patient include age over 50 years and malnutrition. Dr Allegretti detailed various types of therapy for such infectious complications, their associated risks, and the importance of individualizing treatment.

“When we look at our safety pyramid of all of our therapies, steroids really do pose the highest risk with regard to contracting infections in our IBD population,” Dr Allegretti explained. “Treatment really must be individualized, accounting for benefits and risks with each of your patients. Active IBD is also an adverse event; if your patient is not responding to the therapy you selected, you really need to switch treatment.”

Dr Allegretti reported that data show ustekinumab resulted in no increased infection frequency compared with placebo (2.3% vs. 2.3%); and a lower rate of tuberculosis reactivation with ustekinumab  than with anti-tumor necrosis factor (TNF) agents. In the Psoriasis Longitudinal and Assessment Registry  ustekinumab was found to have an infection rate of 1.3 per 100 patient-years when compared with infliximab at 5.74 per 100 patient-years.

Among the anti-integrin therapies, vedolizumab showed no increased risk of infection or serious infection overall. Serious risks in data from the GEMINI study group included young age, steroid use, and use of narcotics.

For Clostridioides diffile (CDI) infections, the prevalence is 2.5-8-fold higher among patients with IBD than among non-IBD patients and patients with IBD have a 4.5-fold higher risk of recurrence, she explained. “Patients with colitis are at the highest risk,” reported Dr Allegretti. “There are many sequela of CDI in IBD, such as exacerbations of IBD, increased hospitalizations, increased length of stay, escalation in IBD therapy, colectomy, higher mortality rates, failure of CDI medical therapy, more CDI recurrences and increased health care costs.”

She continued, “The diagnosis of CDI in IBD can be confusing. We know CDI can present with atypical features and may develop without antibiotic use, at a younger age, and these patients are often colonized. So distinguishing colonization from active infection can be quite tricky. Most notably, there is symptom overlap. Differentiation can be quite difficult, which is why all patients with IBD presenting with worsening symptoms should be tested for CDI initially. I think talking about testing is quite critical.”

Dr Allegretti explained how most physicians testing for CDI have switched to PCR-only testing, which has its drawbacks, but she explained the newest versions of the toxin test are much better. “That being said, many of us still use PCR in practice, and the issue with PCR is that it detects the gene that codes for toxin, it does not actually detect toxin itself, so you cannot distinguish colonization with active infection when you use PCR only, which is important to note, “ Dr Allegretti explained.

There are many challenges in the treatment of CDI in IBD, including limited data, and clinical trials often exclude patients with IBD. IBD should be considered a CDI severity marker, “meaning, you should be starting with vancomycin or fidaxomycin. You should not be using metronidazole with this patient population,” Dr Allegretti reported.

The current solution to worsening underlying infection with immunosuppression, which is required to manage flares cause by CDI, is both antibiotics and immunosuppression. When gastroenterologists were surveyed, data was mixed, showing that 46% add immunosuppression to antibiotics, and 54% use antibiotics alone.

Dr Allegretti concluded with a reminder of the high risk levels when using steroids to treat patients with IBD, the importance of individualized therapy, and the half-lives of biologics.“It’s always important to keep in mind, the half-life of our biologics are quite long. So take that into consideration when you’re considering restarting therapy; it can take 6 to 8 weeks to fully clear in patients, which is an important consideration in treatment management,” Dr Allegretti concluded.  

-Angelique Platas

Reference:

Allegretti J. Management of infections in the immunosuppressed IBD patient. Presented at: Advances in Inflammatory Bowel Diseases virtual regional meeting. March 6, 2021