Safety Is Stacking Biologics Safe? All biologic and small molecule medications come with side effects, and pairing them may increase your risk .e60dc2a1-f33c-4a05-9b50-8e3e8e597629d7eeaf8e-a943-44d5-9698-9532af643cf9 Stacking medications could increase your risk of infections. Other common side effects while taking dual therapy include headaches, nausea, and respiratory or sinus infections.e60dc2a1-f33c-4a05-9b50-8e3e8e5976295a04f716-7833-4499-a366-fa0af5d7c3d8 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. Ali feels most comfortable combining a gut-specific therapy, like vedolizumab (Entyvio), with another agent like an interleukin-23 (IL-23) inhibitor. The only IL-23 inhibitor approved for Crohn’s is risankizumab-rzaa (Skyrizi), but others are being researched.e60dc2a1-f33c-4a05-9b50-8e3e8e59762967badd71-4191-43a3-9f7f-e0a10761117d 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.
Biologic medications improve inflammation in Crohn’s disease by blocking immune system proteins that cause it. By doing this, these drugs decrease symptoms, lower your risk of flares, and help the lining of your intestine heal.e60dc2a1-f33c-4a05-9b50-8e3e8e597629b534e6a9-6a01-47c5-bf34-06cb928149fc But for moderate to severe Crohn’s that doesn’t respond well to one biologic drug, you can sometimes add a second biologic or a small molecule drug, another form of advanced therapy — a tactic called biologic stacking, or dual therapy. Below, learn how stacking biologics works in Crohn’s disease and whether you may be eligible for this approach.e60dc2a1-f33c-4a05-9b50-8e3e8e5976291dac3ff5-dfbc-448c-b3fc-1a80b209518f
Should You Try It? 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.” Since experts don’t have much data and these drugs have a high price tag, dual therapy isn’t right for everyone, says Philpott, who believes that they should only be used with great care.e60dc2a1-f33c-4a05-9b50-8e3e8e597629840dede1-f639-4d67-b44c-0a36edc266f0 “But it can give us hope and success for patients that have struggled up to now to gain control of their disease.” 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. Biologic stacking can also work well for people with extraintestinal manifestations (EIMs) — complications that can occur in the blood, joints, skin, eyes, kidneys, liver, and bones.e60dc2a1-f33c-4a05-9b50-8e3e8e597629966655dd-e0a6-42a5-8c07-5591ad0c7915e60dc2a1-f33c-4a05-9b50-8e3e8e597629ef02fdda-b9b6-4e09-9947-491fc1bd2bcc You may also benefit from a more aggressive combined approach if you have perianal fistulizing Crohn’s disease, which can be particularly challenging to treat, says Ali. This Crohn’s complication causes tunnels ( fistulas ) to form between the intestines and other organs, or the skin.e60dc2a1-f33c-4a05-9b50-8e3e8e597629f3730ee0-3bff-410d-a629-45f893c71c3a 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 One aspect to think about when considering dual therapy is the cost. “Even when biologic stacking makes sense clinically, access can be a major barrier,” says Ali.e60dc2a1-f33c-4a05-9b50-8e3e8e597629714b255f-0610-4258-a055-2a514e065f31 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.” Philpott hopes for more future studies on dual therapy to better guide how to prescribe this treatment option and provide more insurance coverage. In the meantime, it may be possible to qualify for financial assistance programs sponsored by drug manufacturers.e60dc2a1-f33c-4a05-9b50-8e3e8e597629aeecc5e4-c722-4503-a8bb-44067098134f
The Takeaway Stacking biologics in Crohn’s disease, also called dual therapy, means adding a second biologic medication or another advanced therapy to your treatment regimen, for better symptom management and intestinal healing. Experts are still researching the safety and efficacy of mixing biologic or small molecule medications, but early results suggest some combinations may be safe and effective. You can ask your gastroenterologist if stacking biologics or small molecule therapies may be an option for you, now or in the future.
Resources We Trust Mayo Clinic: Biologic Treatment for Crohn’s Disease — Comparing the Different Classes of MedicineCleveland Clinic: Biologics (Biologic Medicine)Crohn’s & Colitis Foundation: Medication Options for Crohn’s DiseaseNational Institute of Diabetes and Digestive and Kidney Diseases: Treatment for Crohn’s DiseaseUniversity of Chicago Medicine: Biologics and Inflammatory Bowel Disease (IBD)
Definition What Does ‘Stacking Biologics’ Mean? Crohn’s inflammation can be generated via a number of routes.e60dc2a1-f33c-4a05-9b50-8e3e8e59762979e4e6e1-cc7d-4b82-a160-7eaeecf06319 Though a biologic drug may block one pathway, inflammation can still happen through other routes.e60dc2a1-f33c-4a05-9b50-8e3e8e597629bb15df50-9774-4509-bde1-5522b64783df That’s why many people with inflammatory bowel diseases (IBDs) like Crohn’s don’t respond to their first biologic or small molecule therapy.e60dc2a1-f33c-4a05-9b50-8e3e8e59762952fe60b5-f198-4ef0-806a-d136642ce830 But when you add another biologic or small molecule medication to your treatment, you block another inflammation pathway, and increase your chances of reducing symptoms and inflammation in the digestive tract.e60dc2a1-f33c-4a05-9b50-8e3e8e597629f13fa7e4-66bb-4df2-9827-2ccbaaadd673 “Each medication targets a different pathway in the immune system that drives inflammation and damages the gut. So instead of targeting one pathway at a time, we are approaching the disease from two angles to achieve better control,” says Tauseef Ali, MD , a gastroenterologist and the medical executive director of SSM Health St. Anthony Digestive Care in Oklahoma City, Oklahoma.e60dc2a1-f33c-4a05-9b50-8e3e8e597629c9a97e7c-7d8d-4f65-b79e-6ef45918bc60 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.