Is Stacking Biologics Safe if You Have Crohn’s Disease?

What Does ‘Stacking Biologics’ Mean?

Dual therapy may also offer better results than switching to a different advanced therapy, especially if you see some improvement on the first drug, says Jessica Philpott, MD, PhD, a gastroenterologist at Cleveland Clinic.

Is Stacking Biologics Safe?

But research on these side effects is still limited, says Ali. “Most of the evidence comes from real-world experience and observational studies rather than large randomized clinical trials.”

“What we have seen so far is somewhat reassuring,” says Ali. “But the studies are small and involve different patient populations, so we have to interpret them cautiously.”

To guard against side effects, Dr. Philpott prefers not to prescribe two advanced therapies that suppress the immune system at a higher level than other options.

But combining advanced therapies isn’t yet a universally accepted strategy, and research evidence is still developing, says Ali, who considers each person carefully before prescribing dual therapy and then monitors them closely during treatment.

“The goal is not simply to use more medication, but to use smarter, more targeted therapy when needed,” says Ali.

Should You Consider Stacking Biologics?

If you want to try stacking a biologic with another biologic or small molecule drug, your healthcare team can help you decide on the best way forward. “As with all IBD therapy, we are always weighing the risk and the benefit,” says Philpott. “The risk of incompletely treated Crohn's, in particular for a patient with severely destructive disease, is very real.”

Who Benefits From Biologic Stacking?

Dual therapy can offer a better chance of treatment success in some situations. “If the patient has been on numerous therapies without great success, and on their current therapy they have had a response, but not full remission, then I consider adding a second medication,” says Philpott.

Stacking vs. Switching

“Before making any change, I take a step back and make sure we are dealing with a true active disease,” says Ali. That means using labs or endoscopy or other imaging, such as a CT or MRI scan, to confirm there is ongoing inflammation, and not an overlapping condition, such as irritable bowel syndrome (IBS), an infection, or a structural issue like a stricture.

"I tend to consider stacking when a patient is getting some benefit but not enough, or when different aspects of the disease are not controlled by one medication,” Ali says. “[W]hereas I switch therapies when the current drug is clearly not working at all. For example, if a patient with Crohn’s disease is on an anti-TNF therapy and has had some improvement in their intestinal symptoms but still has active perianal fistulas or persistent inflammation on endoscopy, I may consider adding a second agent to target a different pathway.”

“In contrast, if that same patient had no meaningful improvement at all despite adequate drug levels [in the blood], I would be more likely to switch to a different class of therapy rather than stack," Ali says.

Barriers to Access

Using two advanced therapies together is often considered off-label (not approved by the U.S. Food and Drug Administration), which means insurance approval is not guaranteed, says Ali. “Prior authorizations can be complex; approvals can be inconsistent, and denials are not uncommon.”

Even when dual treatments are approved, your copay could still be high, Ali says. “At the end of the day, the best treatment plan is not just what works scientifically, but what is realistically achievable for the person sitting in front of us.”