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February 20, 2020
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Infections, malignancy risk in IBD must be considered individually

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MAUI, Hawaii — Certain inflammatory bowel disease therapies may further increase malignancies in patients with Crohn’s disease or ulcerative colitis, according to an expert at the GUILD Conference 2020.

“We need to think about each individual patient as different with different characteristics and different individual risk factors,” Millie D. Long, MD, MPH, associate professor of medicine, vice chief for education and director of the gastroenterology and hepatology fellowship program at the Inflammatory Bowel Diseases Center at the University of North Carolina-Chapel Hill, said during her presentation. “If you look over at a 65-year-old man with extensive colitis, they have a pretty high risk of colorectal cancer. And so, when you think about withdrawing a thiopurine in that patient, you really have to think about what that whole virtual cancer risk will do.”

Serious and opportunistic infections are also associated with IBD. Risk factors for both types of infections are immunosuppression therapy, exposure to pathogens, geographic clustering, age, comorbidities and malnutrition. Age is an independent risk factor regardless of the medications a patient is on at an odds ratio of 1.1 per 5 years.

Different medications may specifically increase risk for skin cancer in patients with IBD, Long said. Tofacitinib (Xelianz, Pfizer) was associated with a higher prevalence of all-cause infection vs. placebo (40% vs. 24%) with a risk for herpes zoster with a hazard ratio of 1.4 in 5% of patients treated with higher doses of tofacitinib. Ustekinumab (Stelara, Janssen) showed an infection rate of 1.3 per 100 person years in the PSOLAR registry with no lower rate of TB reactivation compared with anti-TNF. Vedolizumab (Entyvio, Takeda) showed no overall increased risk for either infection but did show higher rates of GI infection than placebo.

The overall cancer risk in Crohn’s disease is increased with a standardized incidence ratio of 1.3, mainly driven by skin cancer, liver/bile cancer and colorectal cancer. For UC, the overall increased risk for cancer appeared in patients with longer standing UC in the second decade.

The absolute risk is highest for colorectal cancer.

“Making an impact with [IBD] therapies when presenting to patients can be very important,” Long said, because the risk for cancer persists after discontinuation of thiopurines. If patients have very active IBD, the risk for surgery in the next 5 years could grow to 50%, according to Long.

“When we think about talking to our patients, really, it’s much better to talk in from the numbers of absolute risks. ... Relative risk is a difficult concept and really being able to have a patient truly understand these risks talking about the absolute risk can be helpful,” Long said. “We have to talk about what these risks are in an absolute fashion as compared to the risks of active untreated disease, and they're able to see that differential and it can help in terms of concerns surrounding initiating therapy.” – by Erin T. Welsh

Reference: Long MD. IBD Therapy Safety with Infection or Malignancy. Presented at: GUILD Conference 2020; February 16-19, 2020; Maui, Hawaii.

Disclosures: Long reports being a consultant for AbbVie, UCB, Janssen, Target PharmaSolutions, Prometheus, Salix and Valeant; received grants and was a consultant for Pfizer and Takeda.