Balancing the Risks of Uncontrolled Crohn’s vs. Biologics

For many people newly diagnosed with moderate to severe Crohn’s disease, the idea of starting a biologic medication can feel intimidating.

But gastroenterologists often frame the decision differently with their patients: It isn’t simply about whether biologics carry risks. It’s about comparing those risks to the long-term consequences of having Crohn’s disease that isn’t well controlled.

In modern inflammatory bowel disease (IBD) care, experts say that the danger of ongoing, uncontrolled inflammation that can lead to irreversible gut damage usually outweighs the relatively rare risks associated with targeted biologic therapies.

Crohn’s disease is a chronic inflammatory condition that can progressively damage the digestive tract if inflammation remains active. This is why disease management is about early, sustained control of inflammation, not just symptom relief, according to Alan Moss, MD, the chief scientific officer at the Crohn’s & Colitis Foundation and a professor of gastroenterology at Boston University's Chobanian and Avedisian School of Medicine.

“When Crohn’s inflammation smolders for months or years, the bowel wall tries to heal by laying down scar tissue. Over time that scarring can turn a soft, inflamed segment into a stiff, narrowed segment we call a fibrotic stricture,” says Dr. Moss.

If inflammation penetrates deeper into the intestinal wall, other complications can develop.

“If inflammation keeps breaking through the bowel wall instead of healing, it can tunnel to nearby loops of intestine, the skin, or other organs, forming fistulas and sometimes pockets of pus called abscesses,” he says.

In Crohn’s, bowel damage tends to be cumulative over time, and once scar tissue and strictures occur, much of that structural change is “effectively irreversible,” says Moss.

That precision marks a shift from older Crohn’s treatments, such as corticosteroids like prednisone, which reduce inflammation throughout the entire body, says Anish Sheth, MD, a gastroenterologist and co-director of the Center for Digestive Health at Penn Medicine Princeton Health in Plainsboro, New Jersey. “Biologics are antibody-based treatments to control, in this case, inflammation,” Dr. Sheth says. “They’re newer drugs targeting receptors and molecules that we call gut specific. They’re exerting their effect in very limited places.”

“We’ve known for 15 years or more that’s not the right approach,” Sheth says. “What happens is that you let the disease go on for years before you finally get it under control.”

“When patients read biologic labels, the words that can stand out are ‘serious infection,’ ‘lymphoma,’ and ‘other cancers,’ and that fear is completely understandable,” Moss says. “The reassuring piece is that, in large studies, those complications are uncommon.”

“Biologics can feel like heavy medications, but doing nothing also carries serious risks, including ongoing inflammation, hospitalizations, and potential surgery, so we need to compare those risks side by side for your specific situation,” Moss says.

When assessing risk with his patients, he reminds them of these points:

• For many people, biologics actually lower long-term complications and improve quality of life by controlling inflammation early and effectively.
• Your healthcare team will monitor you closely to minimize and manage side effects.
• The medical community’s comfort level with using biologics is much higher than it was in the past, and it now has over 20 years’ experience with this class of drug.

Several classes of biologic drugs are used to treat Crohn’s disease. They all work to reduce inflammation, but they target different parts of the immune system and have slightly different safety profiles.

Anti-TNF Drugs

“These drugs have the longest track record and work very well for many patients,” Moss says.

But because anti-TNFs suppress immune activity more broadly throughout the body, they may carry a somewhat higher risk of infections.

“For many of my patients, I frame it this way: The older anti-TNF drugs like Remicade and Humira have the longest track record and work well, but they do carry a somewhat higher risk of serious infections, especially when combined with other immune-suppressing medicines,” Moss says.

Anti-TNFs are still commonly used today, particularly for people with fistulizing Crohn’s disease, those who are pregnant, and patients with inflammatory symptoms outside the digestive tract, such as arthritis or skin conditions, Sheth says.

IL-12/23 and IL-23 Inhibitors

Newer biologics, including IL-12/23 and IL-23 inhibitors, target more specific immune pathways involved in Crohn’s disease.

“With newer IL-23 inhibitors like Stelara and Skyrizi, large trials and real-world studies suggest [that there are] fewer serious infections and fewer issues with antibodies,” Moss says. “That means people are often able to stay on them longer without needing to stop or switch.”

Because these medications act more selectively on the immune system, many specialists describe them as having a more gut-focused effect, which may help reduce systemic side effects compared with earlier biologic therapies.

Doctors take several steps to minimize potential complications before and during biologic therapy, according to Moss:

• Before starting treatment, patients typically undergo comprehensive screening tests to identify conditions that could increase the risk of infection. These often include blood tests, chest X-rays, and a vaccine review to identify and treat silent infections (like tuberculosis and hepatitis).
• During treatment, doctors focus on therapeutic drug monitoring (regular checks of blood work, drug levels, and antibodies) to guide them in maintaining a patient’s sweet spot, so they’re less likely to lose response, have a flare, or run into preventable side effects.

Beyond tests, your doctor will also follow safety protocols, such as avoiding unnecessary combinations of immune-suppressing drugs and ensuring you stay up to date on vaccinations, Moss says. If necessary, they will adjust your treatment plan.

When Sheth works with his patients, he shares statistics pointing to strong safety data and offers patients a trial period.

“I’ll tell them, 'Try it for three to six months and see what it does for your diarrhea, abdominal pain, energy, and quality of life.' If the benefits aren’t enough or they have side effects, we can stop it,” he says. “But most patients end up saying they feel better than they have in years and don’t want to come off.”

These strategies have helped make biologic therapy safer and more predictable than ever before.

• Untreated Crohn’s disease can cause progressive inflammation that leads to complications such as strictures, fistulas, infections, and bowel damage over time.
• Biologic medications, or biologics, are lab-made therapies designed to target specific immune pathways driving inflammation, rather than suppressing the entire immune system.
• While biologics carry some risks, serious side effects are relatively rare compared with the long-term complications associated with uncontrolled Crohn’s disease.
• Working closely with a gastroenterologist, including undergoing recommended screenings and monitoring, can help reduce risks and improve treatment outcomes.